A Phase 3, Multicenter, Randomized, Double-blind Study of a Single Dose of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir 75 mg Twice Daily for 5 Days in Otherwise Healthy Patients With Influenza
Latest Information Update: 26 May 2022
At a glance
- Drugs Baloxavir-marboxil (Primary) ; Oseltamivir
- Indications Influenza virus infections
- Focus Registrational; Therapeutic Use
- Acronyms CAPSTONE 1
- Sponsors Shionogi
- 18 May 2022 Results by deriving data from JapicCTI-153090, NCT02954354; NCT02949011, NCT03959332; KCT0003535, developing pharmacokinetics-time to alleviation of symptoms (PK-TTAS) model to study Baloxavir Marboxil Clinical Efficacy in Different Ethnic Groups with Influenza A or B.published in the Clinical Pharmacology and Therapeutics
- 24 Jun 2021 Results of comparative analysis of baloxavir pharmacokinetics and simulated efficacy in chinese individuals and asian patients by using data of baloxavir clinical trials (a Phase I study (NCT03959332), a Phase II study (OwH; T0821), and Phase III studies in OwH (NCT02954354) and high risk (NCT02949011)), presented at the World Microbe Forum 2021.
- 24 Jun 2021 Result (n=1781) of population pharmacokinetics model analysis from phase 2/3 data three studies (NCT02954354; NCT02949011 and NCT03959332) assessing the potential differences imposed by ethnicity on the PK-TTAS relationship that would justify a dose adaptation in Chinese patients, presented at the World Microbe Forum 2021.
Most Recent Events
Trial Overview
Outcome
Purpose
The primary objective of this study is to evaluate the efficacy of a single, oral dose of baloxavir marboxil compared with placebo by measuring the time to alleviation of symptoms in patients with uncomplicated influenza virus infection.
Comments
According to a Roche media release, the European Commission (EC) has approved Xofluza (baloxavir marboxil) for the treatment of uncomplicated influenza in patients aged 12 years and above. In addition, the EC has approved Xofluza for post-exposure prophylaxis of influenza in individuals aged 12 years and above.
According to an Shionogi media release, the company announced that Xofluza has been approved in Taiwan for the treatment of acute influenza Types A and B in patients 12 years of age and older(As of August 28, 2019).
According to a Roche media release, the U.S. FDA has approved Xofluza (baloxavir marboxil) for the treatment of acute uncomplicated influenza (flu) in patients 12 years of age and older, based on results from this phase III CAPSTONE-1 study and phase II study in otherwise healthy people with the flu (JapicCTI153090) (as of 24 Oct 2018).
According to Shionogi media release,company Filed for the New Drug Application of Baloxavir Marboxil in Taiwan for the Treatment of Influenza( as of 2 Jul 2018).
Based on the results from this study , XOFLUZATM (baloxavir marboxil) tablets 10mg/20mg has been approved in Japan by the Ministry of Health, Labour and Welfare for the treatment of Influenza Types A and B (as of 23 Feb 2018).
Primary Endpoints
Time to alleviation of symptoms
safety_issue: No
description: Time to alleviation of symptoms is defined as the time between the initiation of the study treatment and the alleviation of influenza symptoms. The alleviation of influenza symptoms is defined as the time when all of 7 influenza symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) have been assessed by the patient as being alleviated at each prespecified time point.
time_frame: From Day 1 pretreatment (baseline) up to Day 14 [1]
Other Endpoints
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
description: Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. Positive influenza virus titer was defined as virus titer not less than the lower limit of quantification (0.7 log₁₀ of the 50% tissue culture infective dose (TCID₅₀/mL) among those assessed for virus titer on Days 2, 3, 4, 5, 6 and 9. time_frame: Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
description: Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. Positive influenza virus titer was defined as virus titer not less than the lower limit of quantification (0.7 log₁₀ of the 50% tissue culture infective dose (TCID₅₀/mL) among those assessed for virus titer on Days 2, 3, 4, 5, 6 and 9. time_frame: Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo
description: Influenza virus ribonucleic acid (RNA) was quantified from nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible). The percentage of participants with detectable virus RNA (2.05 for flu A and 2.83 for flu B log₁₀ virus particles/mL) among those assessed measured by reverse transcription polymerase chain reaction (RT-PCR) on Days 2, 3, 4, 5, 6 and 9. time_frame: Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
description: Influenza virus RNA was quantified from nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible). The percentage of participants with detectable virus RNA (2.05 for flu A and 2.83 for flu B log₁₀ virus particles/mL) among those assessed measured by reverse transcription polymerase chain reaction (RT-PCR) on Days 2, 3, 4, 5, 6 and 9. time_frame: Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
description: Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. If virus titer was less than the lower limit of quantification, the virus titer was imputed 0.7 (TCID₅₀/mL). time_frame: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
description: Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. If virus titer was less than the lower limit of quantification, the virus titer was imputed 0.7 (TCID₅₀/mL). time_frame: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo
description: Nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible) were obtained for viral quantitation. Virus RNA is measured by reverse transcription polymerase chain reaction (RT-PCR). time_frame: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
description: Nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible) were obtained for viral quantitation. Virus RNA was measured by reverse transcription polymerase chain reaction (RT-PCR). time_frame: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to Baloxavir or Placebo
description: This endpoint was defined as AUC of change from Baseline in virus titer from Day 1 to Day 9. AUC was calculated using the trapezoidal method. time_frame: Day 1 to Day 9
Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Adults Randomized to Baloxavir or Oseltamivir
description: This endpoint was defined as AUC of change from Baseline in virus titer from Day 1 to Day 9. AUC was calculated using the trapezoidal method. time_frame: Day 1 to Day 9
Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Participants Randomized to Baloxavir or Placebo
description: This endpoint was defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 9. The AUC was calculated using the trapezoidal method. time_frame: Day 1 to Day 9
Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Adults Randomized to Baloxavir or Oseltamivir
description: This endpoint was defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 9. The AUC was calculated using the trapezoidal method. time_frame: Day 1 to Day 9
Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to Baloxavir or Placebo
description: Time to cessation of viral shedding by virus titer was defined as the time between the initiation of the study treatment and first time when the virus titer was below the limit of detection (0.7 log₁₀[TCID₅₀/mL]). The median and 95% confidence interval (CI) for time to cessation of viral shedding determined by virus titer was analyzed using the Kaplan-Meier (KM) method; participants whose virus titer had not reached cessation by the last observation time point were treated as censored at that time point. time_frame: Day 1 to Day 9
Time to Cessation of Viral Shedding Determined by Virus Titer in Adults Randomized to Baloxavir or Oseltamivir
description: Time to cessation of viral shedding by virus titer was defined as the time between the initiation of the study treatment and first time when the virus titer was below the limit of detection (0.7 log₁₀[TCID₅₀/mL]). The time to cessation of viral shedding determined by virus titer was analyzed using the Kaplan-Meier (KM) method; participants whose virus titer had not reached cessation by the last observation time point were treated as censored at that time point. time_frame: Day 1 to Day 9
Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to Baloxavir or Placebo
description: Time to cessation of viral shedding by RT-PCR was defined as the time between the initiation of the study treatment and first time when the virus RNA was below the limit of detection measured by RT-PCR. Time to cessation of viral shedding by RT-PCR was analyzed using the KM method; participants whose virus RNA had not reached cessation by the last observation time point were treated as censored at that time point. time_frame: Day 1 to Day 9
Time to Cessation of Viral Shedding Determined by Virus RNA in Adults Randomized to Baloxavir or Oseltamivir
description: Time to cessation of viral shedding by RT-PCR was defined as the time between the initiation of the study treatment and first time when the virus RNA was below the limit of detection measured by RT-PCR. Time to cessation of viral shedding by RT-PCR was analyzed using the KM method; participants whose virus RNA had not reached cessation by the last observation time point were treated as censored at that time point. time_frame: Day 1 to Day 9
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
description: Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Alleviation of symptoms was defined as all seven influenza-related symptoms assessed by the participant as absent (0) or mild (1) . time_frame: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
description: Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Alleviation of symptoms was defined as all seven influenza-related symptoms assessed by the participant as absent (0) or mild (1) . time_frame: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment
Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to Baloxavir or Placebo
description: Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 4 systemic symptoms was defined as the time between the initiation of the study treatment to the time when all 4 systemic symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue) were assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours. Time to alleviation of the 4 systemic symptoms was analyzed using KM methods; participants who did not experience alleviation of symptoms were censored at the last observation time point. time_frame: Initiation of study treatment up to Day 14
Time to Alleviation of the Four Systemic Symptoms in Adults Randomized to Baloxavir or Oseltamivir
description: Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 4 systemic symptoms was defined as the time between the initiation of the study treatment to the time when all 4 systemic symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue) were assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours. Time to alleviation of the 4 systemic symptoms was analyzed using KM methods; participants who did not experience alleviation of symptoms were censored at the last observation time point. time_frame: Initiation of study treatment up to Day 14
Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to Baloxavir or Placebo
description: Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 3 respiratory symptoms was defined as the time from the start of study treatment to the time when all 3 respiratory symptoms (cough, sore throat and nasal congestion) were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of the 3 respiratory symptoms was analyzed using the KM method; participants who did not experience alleviation of symptoms were censored at the last observation time point. time_frame: Initiation of study treatment up to Day 14
Time to Alleviation of the Three Respiratory Symptoms in Adults Randomized to Baloxavir or Oseltamivir
description: Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 3 respiratory symptoms was defined as the time from the start of study treatment to the time when all 3 respiratory symptoms (cough, sore throat and nasal congestion) were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of the 3 respiratory symptoms was analyzed using the KM method; participants who did not experience alleviation of symptoms were censored at the last observation time point. time_frame: Initiation of study treatment up to Day 14
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
description: Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participant, and ranges from 0 to 21. time_frame: Day 1 pretreatment (Baseline) and 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment.
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
description: Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participant, and ranges from 0 to 21. time_frame: Day 1 pretreatment (Baseline) and 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment.
Time to Resolution of Fever in Participants Randomized to Baloxavir or Placebo
description: Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for a duration of at least 12 hours. Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point. time_frame: Initiation of study treatment up to Day 14
Time to Resolution of Fever in Adults Randomized to Baloxavir or Oseltamivir
description: Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for a duration of at least 12 hours. Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point. time_frame: Initiation of study treatment up to Day 14
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
description: Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment. time_frame: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
description: Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment. time_frame: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment
Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
description: Participant's self-measured axillary temperature using an electronic thermometer. time_frame: 12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment
Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
description: Participant's self-measured axillary temperature using an electronic thermometer. time_frame: 12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment
Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo
description: Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of each symptom was defined as the time from the start of treatment to the start of the time period when the individual symptom was assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours. time_frame: Initiation of study treatment up to Day 14
Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir
description: Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of each symptom was defined as the time from the start of treatment to the start of the time period when the individual symptom was assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours. time_frame: Initiation of study treatment up to Day 14
Time to Return to Preinfluenza Health Status in Participants Randomized to Baloxavir or Placebo
description: Participants were asked to record their preinfluenza health status on a scale from 0 (worst possible health) to 10 (normal health [for someone your age and your health condition]), and their health status every day after initiation of study treatment on the same scale. Return to preinfluenza health status was defined as time from the initiation of the study treatment to the first time when the health status score was equal to or higher than the preinfluenza health status score. Time to return to preinfluenza health status was analyzed using KM methods; participants with a smaller number on the scale for health status by the last observation time point were censored at that time point. time_frame: Initiation of study treatment up to Day 14
Time to Return to Preinfluenza Health Status in Adults Randomized to Baloxavir or Oseltamivir
description: Participants were asked to record their preinfluenza health status on a scale from 0 (worst possible health) to 10 (normal health [for someone your age and your health condition]), and their health status every day after initiation of study treatment on the same scale. Return to preinfluenza health status was defined as time from the initiation of the study treatment to the first time when the health status score was equal to or higher than the preinfluenza health status score. Time to return to preinfluenza health status was analyzed using KM methods; participants with a smaller number on the scale for health status by the last observation time point were censored at that time point. time_frame: Initiation of study treatment up to Day 14
Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo
description: The percentage of participants who experienced each influenza-related complication (hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically confirmed pneumonia) as an adverse event after the initiation of the study treatment. time_frame: Initiation of study treatment up to Day 14
Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir
description: The percentage of participants who experienced each influenza-related complication (hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically confirmed pneumonia) as an adverse event after the initiation of the study treatment. time_frame: Initiation of study treatment up to Day 14
Percentage of Participants With Adverse Events (AEs)
time_frame: From first dose of study drug to Day 22 [2]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| Influenza virus infections | treatment | acute |
Subjects
- Subject Type patients
-
Number
Planned: 1494
Actual: 1436
- Sex male & female
- Age Group 12-64 years; adolescent; adult; child
Patient Inclusion Criteria
1. Patients who are able to understand the study and comply with all study procedures, and willing to provide written informed consent/assent prior to the predose examinations appropriately. As for adolescent patients, informed consent/assent of voluntary participation should be obtained in accordance with local requirements 2. Male or female patients aged ≥ 12 to ≤ 64 years at the time of signing the informed consent/assent form. 3. Patients with a diagnosis of influenza virus infection confirmed by all of the following: 1. Fever ≥ 38ºC (axillary) in the predose examinations or > 4 hours after dosing of antipyretics if they were taken 2. At least one of the following general systemic symptoms associated with influenza are present with a severity of moderate or greater - Headache - Feverishness or chills - Muscle or joint pain - Fatigue 3. At least one of the following respiratory symptoms associated with influenza are present with a severity of moderate or greater - Cough - Sore throat - Nasal congestion 4. The time interval between the onset of symptoms and the predose examinations is 48 hours or less. The onset of symptoms is defined as either: 1. Time of the first increase in body temperature (an increase of at least 1ºC from normal body temperature) 2. Time when the patient experiences at least one general or respiratory symptom 5. Women of childbearing potential who agree to use a highly effective method of contraception for 3 months after the first dose of study drug
Patient Exclusion Criteria
1. Patients with severe influenza virus infection requiring inpatient treatment. 2. Patients aged ≥ 20 years with known allergy to oseltamivir (Tamiflu®). 3. Patients with any of the following risk factors 1. Women who are pregnant or within 2 weeks post-partum 2. Residents of long-term care facilities (eg, welfare facilities for the elderly, nursing homes) 3. Chronic respiratory diseases including bronchial asthma 4. Neurological and neurodevelopmental disorders including disorders of the brain, spinal cord, peripheral nerve, and muscle (eg, cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury) 5. Heart disease (such as congenital heart disease, congestive heart failure, or coronary artery disease), excluding hypertension without any other heart-related symptoms) 6. American Indians and Alaskan natives 7. Blood disorders (such as sickle cell disease) 8. Endocrine disorders (including diabetes mellitus) 9. Kidney disorders 10. Liver disorders 11. Metabolic disorders 12. Compromised immune system (including patients receiving immunosuppressant therapy, or those with cancer or human immunodeficiency virus [HIV] infection) 13. Morbid obesity (body mass index [BMI] ≥ 40) 4. Patients unable to swallow tablets or capsules. 5. Patients who have previously received Baloxavir Marboxil. 6. Patients weighing < 40 kg 7. Patients who have been exposed to an investigational drug within 30 days prior to the predose examinations. 8. Women who are breastfeeding or have a positive pregnancy test in the predose examinations. The following female patients who have documentation of either a or b below do not need to undergo a pregnancy test in the predose examinations: 1. Postmenopausal (defined as cessation of regular menstrual periods for 2 years or more and confirmed by a follicle-stimulating hormone test) women 2. Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or tubal ligation 9. Patients with concurrent infections requiring systemic antimicrobial and/or antiviral therapy at the predose examinations. 10. Patients who have received peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir, or amantadine within 30 days prior to the predose examinations. 11. Patients who have received an investigational monoclonal antibody for a viral disease in the last year. 12. Patients with severe underlying diseases. 13. Patients with known creatinine clearance ≤ 60 mL/min. 14. Patients who, in the opinion of the investigator, would be unlikely to comply with required study visits, self-assessments, and interventions
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT02954354 | ClinicalTrials.gov: US National Institutes of Health |
| 1601T0831 | - |
Organisations
- Sponsors Shionogi
- Affiliations Genentech; Roche; Shionogi
Trial Dates
-
Initiation Dates
Planned : 01 Nov 2016
Actual : 08 Dec 2016
-
Primary Completion Dates
Planned : 01 May 2017
Actual : 04 Apr 2017
-
End Dates
Planned : 01 Oct 2017
Actual : 24 Apr 2017
Other Details
- Design double-blind; multicentre; parallel; prospective; randomised
- Phase of Trial Phase III
- Location Canada; Japan; USA
- Focus Registrational; Therapeutic Use
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| Baloxavir-marboxilPrimary Drug | Oral | Tablet |
| Oseltamivir | Oral | Capsule |
Adolescents: Baloxavir Marboxil
Participants aged 12 to 19 years will receive two or four baloxavir marboxil 20 mg tablets on Day 1. Drug: Baloxavir Marboxil (2 to4 X 20-mg tablets taken orally) Other Name: S-033188
Adults: Baloxavir Marboxil
Participants aged 20 to 64 years will receive two or four 20 mg baloxavir marboxil tablets orally on Day 1 and one oseltamivir placebo capsule orally twice a day (BID) on Days 1 to 5. Drug: Baloxavir Marboxil (2 to4 X 20-mg tablets taken orally) Other Name: S-033188 Drug: Placebo to Oseltamivir (Placebo capsules matching oseltamivir 75 mg capsules)
Adolescents: Placebo
Participants aged 12 to 19 years will receive two or four baloxavir marboxil placebo tablets on Day 1. Drug: Placebo to Baloxavir Marboxil (2 to4 X 20-mg tablets taken orally)
Adults: Oseltamivir
Participants aged 20 to 64 years will receive 75 mg oseltamivir twice a day on Days 1 to 5 and two or four baloxavir marboxil placebo tablets on Day 1. Drug: Placebo to Baloxavir Marboxil (2 to4 X 20-mg tablets taken orally) Drug: Oseltamivir (75 mg capsules taken orally) Other Name: Tamiflu®
Adults: Placebo
Participants aged 20 to 64 years will receive two or four baloxavir marboxil placebo tablets on Day 1 and one oseltamivir placebo capsule orally twice a day on Days 1 to 5. Drug: Placebo to Baloxavir Marboxil (2 to4 X 20-mg tablets taken orally) Drug: Placebo to Oseltamivir (Placebo capsules matching oseltamivir 75 mg capsules)
Results
Therapeutic efficacy
Phase III: Updated data from the phase III CAPSTONE-1 trial, demonstrated emergence of PAI38X variants as early as 3 days after treatment with baloxavir in 9.7% (36/370) of patients. The median time to alleviation of symptom (TTAS) was reported to be longer in baloxavir recipients shedding PA/I38X virus (63.1 hours) versus those without (51.0 hours) but shorter than in placebo recipients (80.2 hours). The time to sustained cessation of infectious virus detection was longer in those with I38X substitutions, of whom % showed transient increases in viral titers, compared to those without and to placebo (median, 192 versus 48 versus 96 hours). The proportion with symptom rebound was similar across these subgroups (11.5, 8.0, and 13.0 percentage, respectively). NGS in 7 selected patients revealed that PA/I38X virus was first detected 3 to 5 days after baloxavir treatment. The susceptibility to baloxavir was reported to be reduced by 65 to 155-fold versus wild-type virus (0.31 - 0.69 ng/mL vs 36 - 63 ng/mL), in five pairs of clinical isolates with PA/I38 variants [3] . Earlier results reported significant reduction in time to alleviation of symptoms (TTAS) (p < 0.001) in otherwise healthy patients with influenza infections in the phase III CAPSTONE-1 trial. The median TTAS was 53.7 hours (p < 0.001) in baloxavir marboxil group, compared with 53.8 hours (p = 0.7560) in oseltamivir group and 80.2 hours in placebo group, respectively. TTAS was similar between baloxavir marboxil and oseltamivir groups [4] . Significant improvement compared with placebo or oseltamivir for important virological endpoints was seen. The percentage of patients determined to be positive for influenza virus titer was significantly lower in the baloxavir marboxil group in comparison with the oseltamivir group at one, two and four days from the start of treatment. Additionally, the time to cessation of viral shedding was significantly decreased to 24 hours (p < 0.0001) in the baloxavir marboxil as compared with the 72 hours (p < 0.0001) in oseltamivir group and 96 hours in placebo group. Significant reduced fever by 24 hours (p < 0.0001) compared with 42 hours in placebo. The results were reported from 1 436 patients enrolled in the study [5] [6] [1] .
Adverse events
Phase III: Baloxavir marboxil was well tolerated with a numerically lower overall incidence of adverse events (20.7%) compared with placebo (24.6%) or oseltamivir (24.8%) in patients with influenza infections in the phase III CAPSTONE-1 trial. No new safety signals were identified. The incidence of treatment-related adverse events were comparable to that of placebo arm. Baloxavir marboxil showed a statistically significant decrease in the incidence of treatment-related adverse events compared to oseltamivir (p = 0.0088). The most common adverse events reported were diarrhea (3.0%), bronchitis (2.6%), nausea (1.3%) and sinusitis (1.1%), and all of these adverse events occurred at a lower frequency than placebo. The incidence of nausea was less frequent in patients treated with S 033188, compared to oseltamivir. The results were reported from 1 436 patients enrolled in the study [5] [6] [1] .
Publications
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Shionogi. Shionogi Announces Positive Top-Line Results for S-033188 Phase 3 Study (CAPSTONE-1) in Otherwise Healthy Influenza Patients. Media-Rel 2017;.
Media Release -
Uehara T, Hayden FG, Kawaguchi K, Omoto S, Baba K, Shishido T, et al. Treatment emergent influenza virus variants with reduced baloxavir suscepbility: impact on clinical and virologic outcomes in otherwise healthy outpatients with acute influenza. ECCMID-2019 2019; abstr. O0819.
Available from: URL: http://link.adisinsight.com/Nt23H -
Shionogi. S-033188 Phase 3 CAPSTONE-1 Study Results for Treatment of Influenza Presented at the European Scientific Working Group on Influenza Conference. Media-Rel 2017;.
Media Release -
Shionogi. Shionogi To Present S-033188 Phase 3 CAPSTONE-1 Study Results For Treatment Of Influenza At IDWeek 2017. Media-Rel 2017;.
Media Release -
Shirley M. Baloxavir Marboxil: A Review in Acute Uncomplicated Influenza. . Drugs 2020;.
PubMed | CrossRef Fulltext -
Kawaguchi K, Portsmouth S, Shishido T, Uehara T, Hayden F. Exploring Clinical and Antiviral Efficacy of Baloxavir Marboxil in a Phase 3, Randomized, Double-blind, Placebo- and Active-controlled Study of Otherwise Healthy Adults/Adolescents in Seasonal Influenza: Impact on Regional Participants, Treatment Time and Influenza Type B Virus Infection (CAPSTONE-1 Study). IDW-2018 2018; abstr. 1645.
Available from: URL: https://idsa.confex.com/idsa/2018/webprogram/Paper71167.html -
Liu Y-M, Retout S, Duval V, Jia J, Zou Y, Wang Y, et al. Comparative Analysis of Baloxavir Pharmacokinetics and Simulated Efficacy in Chinese Individuals and Asian Patients. ASM-FEMS-WMF-2021 2021; abstr. N/A.
Available from: URL: https://www.abstractsonline.com/pp8/9286/presentation/9655 -
Portsmouth S, Hayden FG, Kawaguchi K, Shishido T, Tsuchiya K, Uehara T. Clinical, virologic and safety outcomes in otherwise healthy adolescent patients with acute influenza: sub-group analyses in adolescent population from the CAPSTONE-1 phase III clinical trial. ECCMID-2019 2019; abstr. O0817.
Available from: URL: http://link.adisinsight.com/z4KWr -
Portsmouth S, Kawaguchi K, Arai M, Tsuchiya K, Uehara T. Cap-Dependent Endonuclease Inhibitor S-033188 for the Treatment of Influenza: Results from a Phase 3, Randomized, Double-Blind, Placebo- and Active-Controlled Study in Otherwise Healthy Adolescents and Adults with Seasonal Influenza. IDW-2017 2017; abstr. LB-2.
Available from: URL: https://idsa.confex.com/idsa/2017/webprogram/Paper67519.html -
Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, et al. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N-Engl-J-Med 2018;379(10):913-923.
PubMed | CrossRef Fulltext -
ClinicalTrials.gov: US National Institutes of Health - Results. Trial-Reg 2018;.
Available from: URL: https://clinicaltrials.gov/ -
Uehara T, Hayden FG, Kawaguchi K, Omoto S, Hurt AC, De Jong MD, et al. Treatment-Emergent Influenza Variant Viruses With Reduced Baloxavir Susceptibility: Impact on Clinical and Virologic Outcomes in Uncomplicated Influenza. J-Infect-Dis 2019;.
PubMed | CrossRef Fulltext -
Retout S, De Buck S, Jolivet S, Duval V, Cosson V. A Pharmacokinetics-Time to Alleviation of Symptoms Model to Support Extrapolation of Baloxavir Marboxil Clinical Efficacy in Different Ethnic Groups with Influenza A or B. . Clin-Pharmacol-Ther 2022;.
PubMed | CrossRef Fulltext -
Retout S, De Buck S, Jolivet S, Duval V, Cosson V. A Pharmacokinetics-time to Alleviation of Symptoms Analysis to Support Extrapolation of Baloxavir Marboxil Clinical Efficacy Results in Chinese Patients with Influenza A or B Virus Infection. ASM-FEMS-WMF-2021 2021; abstr. N/A.
Available from: URL: https://www.abstractsonline.com/pp8/9286/presentation/9656
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
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Shionogi Clinical Trials Administrator Clinical Support Help Line
800-849-9707
show details
Shionogiclintrials-admin@shionogi.co.jp |
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Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| Shionogi |
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| Shionogi Research Site | Addison, Texas | USA |
| Shionogi Research Site | Akashi-shi, Hyogo | Japan |
| Shionogi Research Site | Amagasaki-city, Hyogo | Japan |
| Shionogi Research Site | Amagasaki-shi, Hyogo | Japan |
| Shionogi Research Site | Athens, Alabama | USA |
| Shionogi Research Site | Austin, Texas | USA |
| Shionogi Research Site | Avon, Indiana | USA |
| Shionogi Research Site | Baytown, Texas | USA |
| Shionogi Research Site | Bellevue, Nebraska | USA |
| Shionogi Research Site | Berlin, New Jersey | USA |
| Shionogi Research Site | Birmingham, Alabama | USA |
| Shionogi Research Site | Boynton Beach, Florida | USA |
| Shionogi Research Site | Bozeman, Montana | USA |
| Shionogi Research Site | Brampton, Ontario | Canada |
| Shionogi Research Site | Brooklyn, New York | USA |
| Shionogi Research Site | Canoga Park, California | USA |
| Shionogi Research Site | Canton, Ohio | USA |
| Shionogi Research Site | Carrollton, Texas | USA |
| Shionogi Research Site | Centennial, Colorado | USA |
| Shionogi Research Site | Centerville, Ohio | USA |
| Shionogi Research Site | Channelview, Texas | USA |
| Shionogi Research Site | Charleston, South Carolina | USA |
| Shionogi Research Site | Charlotte, North Carolina | USA |
| Shionogi Research Site | Chikushino City, Fukuoka | Japan |
| Shionogi Research Site | Chofu-shi, Tokyo | Japan |
| Shionogi Research Site | Chuo-ku, Tokyo | Japan |
| Shionogi Research Site | Cincinnati, Ohio | USA |
| Shionogi Research Site | Clearwater, Florida | USA |
| Shionogi Research Site | Columbus, Georgia | USA |
| Shionogi Research Site | Corpus Christi, Texas | USA |
| Shionogi Research Site | Costa Mesa, California | USA |
| Shionogi Research Site | Dallas, Texas | USA |
| Shionogi Research Site | Dayton, Ohio | USA |
| Shionogi Research Site | Decatur, Georgia | USA |
| Shionogi Research Site | Denver, Colorado | USA |
| Shionogi Research Site | DeSoto, Texas | USA |
| Shionogi Research Site | Diamond Bar, California | USA |
| Shionogi Research Site | Doral, Florida | USA |
| Shionogi Research Site | Draper, Utah | USA |
| Shionogi Research Site | Edogawa-ku, Tokyo | Japan |
| Shionogi Research Site | Ellensburg, Washington | USA |
| Shionogi Research Site | Evansville, Indiana | USA |
| Shionogi Research Site | Fayetteville, North Carolina | USA |
| Shionogi Research Site | Fort Lauderdale, Florida | USA |
| Shionogi Research Site | Fort Myers, Florida | USA |
| Shionogi Research Site | Franklin, Tennessee | USA |
| Shionogi Research Site | Fukui City, Fukui | Japan |
| Shionogi Research Site | Fukuoka | Japan |
| Shionogi Research Site | Fukuoka City, Fukuoka | Japan |
| Shionogi Research Site | Fukuoka-shi, Fukuoka | Japan |
| Shionogi Research Site | Fukutsu-shi, Fukuoka | Japan |
| Shionogi Research Site | Fukuyama City, Hiroshima | Japan |
| Shionogi Research Site | Funabashi City, Chiba | Japan |
| Shionogi Research Site | Gainesville, Florida | USA |
| Shionogi Research Site | Garden City, New York | USA |
| Shionogi Research Site | Gold River, California | USA |
| Shionogi Research Site | Greenbrae, California | USA |
| Shionogi Research Site | Gulf Shores, Alabama | USA |
| Shionogi Research Site | Gunma | Japan |
| Shionogi Research Site | Hakodate City, Hokkaido | Japan |
| Shionogi Research Site | Hakodate-city, Hokkaido | Japan |
| Shionogi Research Site | Harleysville, Pennsylvania | USA |
| Shionogi Research Site | Hawaiian Gardens, California | USA |
| Shionogi Research Site | Hialeah, Florida | USA |
| Shionogi Research Site | Hickory, North Carolina | USA |
| Shionogi Research Site | Higashi-ku, Fukuoka | Japan |
| Shionogi Research Site | Hino City, Tokyo | Japan |
| Shionogi Research Site | Hiroshima | Japan |
| Shionogi Research Site | Hiroshima-shi, Hiroshima | Japan |
| Shionogi Research Site | Houston, Texas | USA |
| Shionogi Research Site | Huntington Beach, California | USA |
| Shionogi Research Site | Huntsville, Alabama | USA |
| Shionogi Research Site | Hyogo | Japan |
| Shionogi Research Site | Ichikawa-city, Chiba | Japan |
| Shionogi Research Site | Ishikawa | Japan |
| Shionogi Research Site | Jackson, Tennessee | USA |
| Shionogi Research Site | Jacksonville, Florida | USA |
| Shionogi Research Site | Johnston, Rhode Island | USA |
| Shionogi Research Site | Kagoshima | Japan |
| Shionogi Research Site | Kagoshima City, Kagoshima | Japan |
| Shionogi Research Site | Kagoshima-shi, Kagoshima | Japan |
| Shionogi Research Site | Kalamazoo, Michigan | USA |
| Shionogi Research Site | Kanazawa-city, Ishikawa | Japan |
| Shionogi Research Site | Kasuga-shi, Fukuoka | Japan |
| Shionogi Research Site | Kasugai City, Aichi | Japan |
| Shionogi Research Site | Kawaguchi, Saitama | Japan |
| Shionogi Research Site | Kawasaki City, Kanagawa | Japan |
| Shionogi Research Site | Kisarazu City, Chiba | Japan |
| Shionogi Research Site | Kissimmee, Florida | USA |
| Shionogi Research Site | Kitakyushu City, Fukuoka | Japan |
| Shionogi Research Site | Kitakyuusyu City, Fukuoka | Japan |
| Shionogi Research Site | Kohriyama City, Fukushima | Japan |
| Shionogi Research Site | Kokubunji-shi, Tokyo | Japan |
| Shionogi Research Site | Koriyama City, Fukushima | Japan |
| Shionogi Research Site | Kumamoto | Japan |
| Shionogi Research Site | Kyoto | Japan |
| Shionogi Research Site | La Crosse, Wisconsin | USA |
| Shionogi Research Site | Lake Charles, Louisiana | USA |
| Shionogi Research Site | Lake Worth, Florida | USA |
| Shionogi Research Site | Lauderdale Lakes, Florida | USA |
| Shionogi Research Site | Lexington, North Carolina | USA |
| Shionogi Research Site | Little Rock, Arkansas | USA |
| Shionogi Research Site | Lomita, California | USA |
| Shionogi Research Site | Long Beach, California | USA |
| Shionogi Research Site | Los Angeles, California | USA |
| Shionogi Research Site | Matsudo-shi, Chiba | Japan |
| Shionogi Research Site | McAllen, Texas | USA |
| Shionogi Research Site | Metairie, Louisiana | USA |
| Shionogi Research Site | Miami, Florida | USA |
| Shionogi Research Site | Mishawaka, Indiana | USA |
| Shionogi Research Site | Miyagi | Japan |
| Shionogi Research Site | Mooresville, North Carolina | USA |
| Shionogi Research Site | Morganton, North Carolina | USA |
| Shionogi Research Site | Musashino City, Tokyo | Japan |
| Shionogi Research Site | Nagoya, Aichi | Japan |
| Shionogi Research Site | Naha City, Okinawa | Japan |
| Shionogi Research Site | Nakano-ku, Tokyo | Japan |
| Shionogi Research Site | Nashville, Tennessee | USA |
| Shionogi Research Site | Nerima-Ku, Tokyo | Japan |
| Shionogi Research Site | New Orleans, Louisiana | USA |
| Shionogi Research Site | New Tazewell, Tennessee | USA |
| Shionogi Research Site | Newmarket, Ontario | Canada |
| Shionogi Research Site | Nonoichi City, Ishikawa | Japan |
| Shionogi Research Site | Norco, California | USA |
| Shionogi Research Site | North Hollywood, California | USA |
| Shionogi Research Site | Northglenn, Colorado | USA |
| Shionogi Research Site | Norwalk, California | USA |
| Shionogi Research Site | Oita City, Oita | Japan |
| Shionogi Research Site | Oita-shi, Oita | Japan |
| Shionogi Research Site | Oklahoma City, Oklahoma | USA |
| Shionogi Research Site | Omaha, Nebraska | USA |
| Shionogi Research Site | Onojo City, Fukuoka | Japan |
| Shionogi Research Site | Orlando, Florida | USA |
| Shionogi Research Site | Osaka | Japan |
| Shionogi Research Site | Osaka City, Osaka | Japan |
| Shionogi Research Site | Osaka-shi, Osaka | Japan |
| Shionogi Research Site | Osaki City, Miyagi | Japan |
| Shionogi Research Site | Ota City, Gunma | Japan |
| Shionogi Research Site | Otsu City, Shiga | Japan |
| Shionogi Research Site | Oxnard, California | USA |
| Shionogi Research Site | Oxon Hill, Maryland | USA |
| Shionogi Research Site | Palos Verdes, California | USA |
| Shionogi Research Site | Paramount, California | USA |
| Shionogi Research Site | Pembroke Pines, Florida | USA |
| Shionogi Research Site | Pharr, Texas | USA |
| Shionogi Research Site | Phoenix, Arizona | USA |
| Shionogi Research Site | Plano, Texas | USA |
| Shionogi Research Site | Rapid City, South Dakota | USA |
| Shionogi Research Site | Rialto, California | USA |
| Shionogi Research Site | Saitama | Japan |
| Shionogi Research Site | Salt Lake City, Utah | USA |
| Shionogi Research Site | San Angelo, Texas | USA |
| Shionogi Research Site | San Antonio, Texas | USA |
| Shionogi Research Site | San Diego, California | USA |
| Shionogi Research Site | San Marino, California | USA |
| Shionogi Research Site | San Ramon, California | USA |
| Shionogi Research Site | Sandy Springs, Georgia | USA |
| Shionogi Research Site | Sapporo City, Hokkaido | Japan |
| Shionogi Research Site | Sarnia, Ontario | Canada |
| Shionogi Research Site | Scottdale, Pennsylvania | USA |
| Shionogi Research Site | Sendai City, Miyagi | Japan |
| Shionogi Research Site | Setagaya-ku, Tokyo | Japan |
| Shionogi Research Site | Shinagawa-ku, Tokyo | Japan |
| Shionogi Research Site | Shinkuju-ku, Tokyo | Japan |
| Shionogi Research Site | Shizuoka City, Shizuoka | Japan |
| Shionogi Research Site | Smithfield, Pennsylvania | USA |
| Shionogi Research Site | Smyrna, Tennessee | USA |
| Shionogi Research Site | Stockton, California | USA |
| Shionogi Research Site | Sugar Land, Texas | USA |
| Shionogi Research Site | Suita City, Osaka | Japan |
| Shionogi Research Site | Suita-shi, Osaka | Japan |
| Shionogi Research Site | Tampa, Florida | USA |
| Shionogi Research Site | Tokyo | Japan |
| Shionogi Research Site | Tomigusuku City, Okinawa | Japan |
| Shionogi Research Site | Toronto, Ontario | Canada |
| Shionogi Research Site | Toshima, Tokyo | Japan |
| Shionogi Research Site | Troy, Michigan | USA |
| Shionogi Research Site | Tsuchiura City, Ibaraki | Japan |
| Shionogi Research Site | Tsukuba City, Ibaraki | Japan |
| Shionogi Research Site | Tucson, Arizona | USA |
| Shionogi Research Site | Tulsa, Oklahoma | USA |
| Shionogi Research Site | Tuscumbia, Alabama | USA |
| Shionogi Research Site | Upland, California | USA |
| Shionogi Research Site | Urasoe City, Okinawa | Japan |
| Shionogi Research Site | Wauconda, Illinois | USA |
| Shionogi Research Site | West Columbia, South Carolina | USA |
| Shionogi Research Site | West Covina, California | USA |
| Shionogi Research Site | West Palm Beach, Florida | USA |
| Shionogi Research Site | Westminster, California | USA |
| Shionogi Research Site | Wichita, Kansas | USA |
| Shionogi Research Site | Winston-Salem, North Carolina | USA |
| Shionogi Research Site | Worcester, Massachusetts | USA |
| Shionogi Research Site | Yanagawa City, Fukuoka | Japan |
| Shionogi Research Site | Yokohama City, Kanagawa | Japan |
| Shionogi Research Site | Yokohama-city, Kanagawa | Japan |
| Shionogi Research Site | Yokohama-shi, Kanagawa | Japan |
| Shionogi Research Site | Yukuhashi City, Fukuoka | Japan |
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 18 May 2022 | Results | Results by deriving data from JapicCTI-153090, NCT02954354; NCT02949011, NCT03959332; KCT0003535, developing pharmacokinetics-time to alleviation of symptoms (PK-TTAS) model to study Baloxavir Marboxil Clinical Efficacy in Different Ethnic Groups with Influenza A or B.published in the Clinical Pharmacology and Therapeutics Updated 26 May 2022 |
| 24 Jun 2021 | Results | Results of comparative analysis of baloxavir pharmacokinetics and simulated efficacy in chinese individuals and asian patients by using data of baloxavir clinical trials (a Phase I study (NCT03959332), a Phase II study (OwH; T0821), and Phase III studies in OwH (NCT02954354) and high risk (NCT02949011)), presented at the World Microbe Forum 2021. Updated 02 Aug 2021 |
| 24 Jun 2021 | Results | Result (n=1781) of population pharmacokinetics model analysis from phase 2/3 data three studies (NCT02954354; NCT02949011 and NCT03959332) assessing the potential differences imposed by ethnicity on the PK-TTAS relationship that would justify a dose adaptation in Chinese patients, presented at the World Microbe Forum 2021. Updated 02 Aug 2021 |
| 11 Jan 2021 | Other trial event | According to a Roche media release, the European Commission (EC) has approved Xofluza (baloxavir marboxil) for the treatment of uncomplicated influenza in patients aged 12 years and above. In addition, the EC has approved Xofluza for post-exposure prophylaxis of influenza in individuals aged 12 years and above. Updated 13 Jan 2021 |
| 13 Nov 2020 | Other trial event | According to a Genentech media release, European Medicines Agencys (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Xofluza(baloxavir marboxil) for the treatment of uncomplicated influenza in patients aged 12 years and above.The CHMP recommendation is based on the results of the phase III CAPSTONE-1, CAPSTONE-2 and BLOCKSTONE studies. Updated 28 Nov 2020 |
| 29 Jun 2020 | Results | Results published in the Drugs Updated 08 Jul 2020 |
| 16 Jan 2020 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 16 Jan 2020 |
| 29 Aug 2019 | Other trial event | According to an Shionogi media release, the company announced that Xofluza has been approved in Taiwan for the treatment of acute influenza Types A and B in patients 12 years of age and older on August 28, 2019. Updated 03 Sep 2019 |
| 16 Jul 2019 | Results | Clinical and virologic outcomes results from the study were published in the Journal of Infectious Diseases. Updated 19 Jul 2019 |
| 16 Apr 2019 | Results | Results assessing clinical and virologic impact of emergence of PA/I38X virus in baloxavir-treated patients presented at the 29th European Congress of Clinical Microbiology and Infectious Diseases Updated 29 May 2019 |
| 16 Apr 2019 | Results | Results reporting subgroup analysis of adolescent patient efficacy, virologic outcomes and safety, presented at the 29th European Congress of Clinical Microbiology and Infectious Diseases. Updated 29 May 2019 |
| 04 Apr 2019 | Other trial event | According to a Shionogi media release, data from the study will be presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2019. Updated 10 Apr 2019 |
| 14 Dec 2018 | Results | Results published in the ClinicalTrials.gov: US National Institutes of Health Trial Registry Updated 29 May 2019 |
| 24 Oct 2018 | Other trial event | According to a Roche media release, the U.S. FDA has approved Xofluza (baloxavir marboxil) for the treatment of acute uncomplicated influenza (flu) in patients 12 years of age and older, based on results from this phase III CAPSTONE-1 study and phase II study in otherwise healthy people with the flu (JapicCTI153090). Updated 31 Oct 2018 |
| 07 Oct 2018 | Results | Results presented at the IDWeek 2018 Updated 08 Nov 2018 |
| 27 Sep 2018 | Other trial event | According to a Shionogi media release, data from the study will be presented compounds at IDWeek™ 2018. Updated 05 Oct 2018 |
| 06 Sep 2018 | Results | Results published in the New England Journal of Medicine Updated 11 Sep 2018 |
| 17 Jul 2018 | Other trial event | According to a Shionogi media release, the company expects that, the US FDA will approve this drug by 24 Dec 2018. Updated 18 Jul 2018 |
| 02 Jul 2018 | Other trial event | According to Shionogi media release,company Filed for the New Drug Application of Baloxavir Marboxil in Taiwan for the Treatment of Influenza. Updated 06 Jul 2018 |
| 25 Jun 2018 | Other trial event | According to a Genentech media release, the US FDA has accepted the New Drug Application (NDA) and granted Priority Review for baloxavir marboxil as a single-dose, oral treatment for acute, uncomplicated influenza in people 12 years and older. The NDA is based on results from this trial. Updated 02 Jul 2018 |
| 23 Feb 2018 | Other trial event | According to a Shionogi media release, based on the results from this study , XOFLUZATM (baloxavir marboxil) tablets 10mg/20mg has been approved in Japan by the Ministry of Health, Labour and Welfare for the treatment of Influenza Types A and B. Updated 27 Feb 2018 |
| 11 Jan 2018 | Other trial event | Canada was the planned location for this trial. Updated 31 Oct 2018 |
| 08 Oct 2017 | Results | Results assessing clinical and virologic outcomes of S-033188 compared with placebo by measuring the time to alleviation of symptoms in patients with uncomplicated influenza virus infection, were presented at the IDWeek 2017. Updated 30 Oct 2017 |
| 05 Oct 2017 | Results | Results presented in a Shionogi Media Release. Updated 10 Oct 2017 |
| 28 Sep 2017 | Other trial event | According to a Shionogi media release, data will be presented at IDWeek 2017. Updated 05 Oct 2017 |
| 13 Sep 2017 | Results | Results presented in the Shionogi Media Release Updated 25 Oct 2017 |
| 13 Sep 2017 | Results | According to a Shionogi media release, results from this trial were released at the 6th European Scientific Working Group on Influenza Conference (ESWI) 2017. Updated 15 Sep 2017 |
| 24 Jul 2017 | Other trial event | According to a Shionogi media release, based on the results from CAPSTONE-1, Shionogi plans to submit a New Drug Application (NDA) to the PMDA in Japan later this year. Updated 26 Jul 2017 |
| 24 Jul 2017 | Endpoint met | Primary endpoint has been met. (Time to alleviation of symptoms), according to a Shionogi media release. Updated 26 Jul 2017 |
| 24 Jul 2017 | Results | Top-line results published in a Shionogi media release. Updated 26 Jul 2017 |
| 08 May 2017 | Status change - completed | Status changed from active, no longer recruiting to completed. Updated 13 May 2017 |
| 30 Mar 2017 | Other trial event | Planned locations for this trial also included Singapore, South Korea and Thailand. Updated 31 Oct 2018 |
| 30 Mar 2017 | Status change - active, no longer recruiting | Status changed from recruiting to active, no longer recruiting. Updated 03 Apr 2017 |
| 28 Feb 2017 | Status change - recruiting | Status changed from not yet recruiting to recruiting. Updated 07 Mar 2017 |
| 14 Nov 2016 | New trial record | New trial record Updated 14 Nov 2016 |
Table of Contents
References
-
Shionogi. Shionogi Announces Positive Top-Line Results for S-033188 Phase 3 Study (CAPSTONE-1) in Otherwise Healthy Influenza Patients. Media-Rel 2017;.
Media Release -
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
Uehara T, Hayden FG, Kawaguchi K, Omoto S, Baba K, Shishido T, et al. Treatment emergent influenza virus variants with reduced baloxavir suscepbility: impact on clinical and virologic outcomes in otherwise healthy outpatients with acute influenza. ECCMID-2019 2019; abstr. O0819.
Available from: URL: http://link.adisinsight.com/Nt23H -
Shionogi. S-033188 Phase 3 CAPSTONE-1 Study Results for Treatment of Influenza Presented at the European Scientific Working Group on Influenza Conference. Media-Rel 2017;.
Media Release -
Genentech. FDA Grants Priority Review to Genentech's Baloxavir Marboxil for the Treatment of Influenza. Media-Rel 2018;.
Media Release -
Shionogi. Shionogi To Present S-033188 Phase 3 CAPSTONE-1 Study Results For Treatment Of Influenza At IDWeek 2017. Media-Rel 2017;.
Media Release -
Shionogi. Shionogi Announces FDA Approval of XOFLUZATM (Baloxavir Marboxil). Media-Rel 2018;.
Media Release -
Shirley M. Baloxavir Marboxil: A Review in Acute Uncomplicated Influenza. . Drugs 2020;.
PubMed | CrossRef Fulltext -
Kawaguchi K, Portsmouth S, Shishido T, Uehara T, Hayden F. Exploring Clinical and Antiviral Efficacy of Baloxavir Marboxil in a Phase 3, Randomized, Double-blind, Placebo- and Active-controlled Study of Otherwise Healthy Adults/Adolescents in Seasonal Influenza: Impact on Regional Participants, Treatment Time and Influenza Type B Virus Infection (CAPSTONE-1 Study). IDW-2018 2018; abstr. 1645.
Available from: URL: https://idsa.confex.com/idsa/2018/webprogram/Paper71167.html -
Liu Y-M, Retout S, Duval V, Jia J, Zou Y, Wang Y, et al. Comparative Analysis of Baloxavir Pharmacokinetics and Simulated Efficacy in Chinese Individuals and Asian Patients. ASM-FEMS-WMF-2021 2021; abstr. N/A.
Available from: URL: https://www.abstractsonline.com/pp8/9286/presentation/9655 -
Roche. Roche announces FDA approval of Xofluza (baloxavir marboxil) for influenza. Media-Rel 2018;.
Media Release -
Roche. CHMP recommends EU approval of Roches Xofluza(Rm) (baloxavir marboxil) for the treatment of influenza. Media-Rel 2020;.
Media Release -
Portsmouth S, Hayden FG, Kawaguchi K, Shishido T, Tsuchiya K, Uehara T. Clinical, virologic and safety outcomes in otherwise healthy adolescent patients with acute influenza: sub-group analyses in adolescent population from the CAPSTONE-1 phase III clinical trial. ECCMID-2019 2019; abstr. O0817.
Available from: URL: http://link.adisinsight.com/z4KWr -
Shionogi. Shionogi Announces Positive Top-Line Results for Baloxavir Marboxil Phase III Study (CAPSTONE-2) in Individuals at High Risk for Influenza-Related Complications. Media-Rel 2018;.
Media Release -
Genentech. Genentech Announces FDA Approval of XOFLUZA (Baloxavir Marboxil) for Influenza. Media-Rel 2018;.
Media Release -
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Shionogi. XOFLUZATM (Baloxavir Marboxil) Tablets 10mg/20mg Approved for the Treatment of Influenza Types A and B in Japan. Media-Rel 2018;.
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Shionogi. Shionogi Announces XOFLUZA(Rm) Tablets 20mg for The Treatment of Influenza Types A and B in Patients 12 years of Age and older Approved in Taiwan. Media-Rel 2019;.
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