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A Randomized, Global, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Once-daily Oral Avatrombopag for the Treatment of Adults With Thrombocytopenia Associated With Liver Disease Prior to an Elective Procedure

Trial Profile

A Randomized, Global, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Once-daily Oral Avatrombopag for the Treatment of Adults With Thrombocytopenia Associated With Liver Disease Prior to an Elective Procedure

Completed
Phase of Trial: Phase III

Latest Information Update: 10 Oct 2018

At a glance

  • Drugs Avatrombopag (Primary)
  • Indications Thrombocytopenia
  • Focus Registrational; Therapeutic Use
  • Acronyms Adapt I
  • Sponsors Dova Pharmaceuticals; Eisai Inc
  • Most Recent Events

    • 10 Oct 2018 Results presented at the American College of Gastroenterology Annual Scientific Meeting and Postgraduate Course 2018
    • 28 Sep 2018 Results from ADAPT 1 and ADAPT 2 studies published in the Journal of Thrombosis and Haemostasis
    • 09 Aug 2018 Mexico was a planned locations for this study.

Trial Overview

Outcome

Primary endpoint met - positive

Purpose

This trial is investigating the efficacy and tolerability of avatrombopag in patients with thrombocytopenia associated with chronic liver disease undergoing an elective procedure.

Comments

Based on the data from ADAPT-1 and ADAPT-2 trials, the U.S. Food and Drug Administration has approved Doptelet (avatrombopag) tablets to treat low blood platelet count (thrombocytopenia) in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure.

Primary Endpoints

Met on 22 Sep 2017

The proportion of participants who require platelet transfusion or rescue therapy for bleed after randomization and up to 7 days after the elective procedure

safety_issue: No
description: To confirm that avatrombopag (60 mg avatrombopag for participants with platelet count less than 40 x 10^9/L and 40 mg avatrombopag for participants with platelet count from 40 to less than 50 x 10^9/L) is superior to placebo in removing the need for platelet transfusions or any rescue procedure for bleeding after randomization and up to 7 days following an elective procedure in participants with chronic liver disease who have thrombocytopenia.
time_frame: Approximately 20 months [1]

Other Endpoints

Percentage of Participants Who Achieved a Platelet Count Greater Than or Equal to 50 x 10^9/L on the Scheduled Procedure Day

description: Responders were defined as participants who achieved a platelet count greater than or equal to 50 x 10^9/L on the procedure day. Participants with missing a platelet count on the procedure day were conservatively considered as not achieving a platelet count of 50x10^9/L in the analysis, (i.e. Non-responders). time_frame: Day 10 to Day 13 (Visit 4)

Change From Baseline in Platelet Count on the Scheduled Procedure Day

description: Last observation carried forward was used for participants with a missing platelet count on the scheduled procedure day. Platelet count was measured preprocedure and before any platelet transfusion. time_frame: Baseline (Visit 2) to Procedure Day 10 to Day 13 (Visit 4)

Percentage of Participants With a World Health Organization (WHO) Bleeding Score Greater Than or Equal to 2 After a Scheduled Procedure

description: The severity of bleeding events was assessed by the investigator (or appropriately delegated study site personnel) using the WHO bleeding scale. The WHO bleeding scale is a clinical investigator-assessed five-point scale with Grade 0 = No bleeding, Grade 1 = Petechial bleeding, Grade 2 = Mild blood loss (clinically significant), Grade 3 = Gross blood loss (requires transfusion (severe)), and Grade 4 = Debilitating blood loss, retinal or cerebral associated with fatality. Participants with missing information are considered as having a WHO bleeding score greater than or equal to 2 in the analysis. time_frame: Baseline (Visit 2) up to 7 days post scheduled procedure

Number of Participants Experiencing an Adverse Event

description: Safety assessments consisted of monitoring and recording all adverse events (AEs) and serious adverse events, including platelet transfusion-related complications; routine laboratory evaluation for hematology, serum chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); the performance of physical examinations; and Doppler sonography. AE severity was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death related to the AE. All AEs graded as 4 or 5 were considered to be serious. Treatment-emergent adverse events (TEAEs) were defined as an AE that started on or after the date of first dose of study drug, up to 30 days after the last dose of study drug. Treatment-related AEs were considered by the investigator to be possibly or probably related to study drug. time_frame: From date of first dose of study drug up to 30 days after the last dose of study drug, up to approximately 3 years [2]

Diseases Treated

Indication Qualifiers Patient Segments
Thrombocytopenia treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 300

    Actual: 231

  • Sex male & female
  • Age Group ≥ 18 years; adult; elderly

Patient Inclusion Criteria

Inclusion Criteria 1. Participants greater than or equal to 18 years of age at Screening with chronic liver disease 2. Participants who have a mean baseline platelet count of less than 50 x 10^9/L. Platelet counts must be measured on 2 separate occasions, during the Screening Period and at Baseline, and must be performed at least one day apart with neither platelet count greater than 60 x 10^9/L. The mean of these 2 platelet counts (mean baseline platelet count) will be used for entry criteria and for assignment to the low or high baseline platelet count cohort. 3. Participants scheduled to undergo a permitted elective procedure who, in the opinion of the investigator, will require a platelet transfusion to address a risk of bleeding associated with the procedure unless there is a clinically significant increase in platelet count from baseline 4. Model For End-stage Liver Disease (MELD) score less than or equal to 24 at Screening 5. If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be stable for 7 days prior to Screening 6. Provide written informed consent 7. Willing and able to comply with all aspects of the protocol

Patient Exclusion Criteria

1. Any history of arterial or venous thrombosis, including partial or complete thrombosis 2. Evidence of thrombosis (partial or complete) in the main portal vein, portal vein branches, or any part of the splenic mesenteric system at Screening 3. Portal vein blood flow velocity rate <10 centimeters/second at Screening 4. Hepatic encephalopathy that cannot be effectively treated 5. Participants with HCC with Barcelona Clinic Liver Cancer (BCLC) staging classification C or D 6. Platelet transfusion or receipt of blood products containing platelets within 7 days of Screening. However packed red blood cells are permitted. 7. Heparin, warfarin, nonsteroidal anti-inflammatory drugs (NSAID), aspirin, verapamil, and antiplatelet therapy with ticlopidine or glycoprotein IIb/IIIa antagonists (eg, tirofiban) within 7 days of Screening 8. Use of erythropoietin stimulating agents within 7 days of Screening 9. Interferon (IFN) use within 14 days of Screening 10. Estrogen-containing hormonal contraceptive or hormone replacement therapy use within 30 days of Screening 11. Active infection requiring systemic antibiotic therapy within 7 days of Screening. However, prophylactic use of antibiotics is permitted. 12. Alcohol abuse, alcohol dependence syndrome, drug abuse, or drug dependence within 6 months of the study start (unless participating in a controlled rehabilitation program) or acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of the study start 13. Elective procedure performed prior to Visit 4 (Procedure Day) 14. Known to be human immunodeficiency virus positive 15. Any clinically significant acute or active bleeding (eg, gastrointestinal, central nervous system) 16. Known history of any primary hematologic disorder (eg, immune thrombocytopenic purpura, myelodysplastic syndrome) 17. Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency, etc.) 18. Participants with a history of significant cardiovascular disease (eg, congestive heart failure New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events [eg, atrial fibrillation], coronary artery stent placement, angioplasty, and coronary artery bypass grafting) 19. Females of childbearing potential who have had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a progesterone-only contraceptive implant/injection, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the participant must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea in the appropriate age group and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) at least 1 month before dosing. 20. Females who are lactating or pregnant at Screening or Baseline (as documented by a positive serum beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. 21. Post liver transplant participants 22. Any participant who has previously received avatrombopag 23. Hypersensitivity to avatrombopag maleate or any of its excipients 24. Hemoglobin levels ≤ 8.0 or ≥ 18.0 g/dL for men and > 15 for women at Screening, with hematocrit ≥ 54% for men and ≥ 45% for women 25. Current malignancy including solid tumors and hematologic malignancies (except HCC) 26. Any history of concomitant medical condition that, in the opinion of the investigator(s), would compromise the participant's ability to safely complete the study 27. Currently enrolled in another clinical trial with any investigational drug or device within 30 days of Screening

Trial Details

Identifiers

Identifier Owner
NCT01972529 ClinicalTrials.gov: US National Institutes of Health
E5501G000-310 Eisai
EudraCT2013-000965-34 European Clinical Trials Database
IRB13-008902 Mayo Clinic
P309-2011 Paediatric Investigation Plan EMA Decision number

Organisations

  • Sponsors Dova Pharmaceuticals; Eisai Inc
  • Affiliations Dova Pharmaceuticals; Eisai Inc

Trial Dates

  • Initiation Dates

    Planned : 01 Jan 2014

    Actual : 01 Feb 2014

  • Primary Completion Dates

    Planned : 01 Dec 2016

    Actual : 26 Jan 2017

  • End Dates

    Planned : 01 Dec 2016

    Actual : 27 Feb 2017

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase III
  • Location Argentina; Australia; Austria; Belgium; Brazil; Canada; Chile; China; England; France; Germany; Hungary; Italy; Poland; Portugal; South Korea; Spain; Taiwan; Thailand; USA
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
AvatrombopagPrimary Drug Oral Tablet

Group A (avatrombopag, lower baseline platelet count)

60 mg avatrombopag (3 x 20 mg tablets) once daily on Days 1 through 5
Drug: avatrombopag (lower baseline platelet count) (60 mg avatrombopag (3 x 20 mg tablets))

Group B (placebo, lower baseline platelet count)

placebo (3 x 20 mg matching placebo tablets) once daily on Days 1 through 5
Drug: placebo (lower baseline platelet count) (60 mg placebo (3 x 20 mg matching placebo tablets))

Group C (avatrombopag, higher baseline platelet count)

40 mg avatrombopag (2 x 20 mg tablets) once daily on Days 1 through 5
Drug: avatrombopag (higher baseline platelet count) (40 mg avatrombopag (2 x 20 mg tablets))

Group D (placebo, higher baseline platelet count)

placebo (2 x 20 mg matching placebo tablets) once daily on Days 1 through 5
Drug: placebo (higher baseline platelet count) (40 mg placebo (2 x 20 mg matching placebo tablets))

Results

Therapeutic efficacy

Thrombocytopenia
The phase III, ADAPT-1 trial met its primary and secondary efficacy endpoints with high statistical significance. In patients with low baseline platelet count (<40 x 109/L) in the ADAPT1 study, 66% of avatrombopag patients did not need platelet transfusion or bleeding rescue, compared with 23% on placebo (p<0.0001). Patients with high baseline platelet count (40 to <50 x 109/L) had significantly less need for platelet transfusion or bleeding rescue (88% vs 38%). Avatrombopag was superior to placebo for both secondary endpoints, increasing mean platelet counts on procedure day to 64 x 109/L. The trial enrolled 231 patients with thrombocytopenia associated with chronic liver disease undergoing an elective procedure [3] .

Adverse events

Phase III: In the phase III, ADAPT-1 and 2 trials, the most common treatment-emergent adverse events (TEAE) were pyrexia, abdominal pain, nausea, fatigue, oedema peripheral and headache, which were similar for placebo and avatrombopag arms in both studies. Most adverse events were mild to moderate in severity. Portal vein thromboses was reported in patients with chronic liver disease and in patients receiving TPO receptor agonists. One treatment-emergent event of portal vein thrombosis was reported in the both studies in an avatrombopag-treated patient (n = 1/430). The thrombotic TEAE occurred with 40mg avatrombopag in cohort 2 in ADAPT2 [4] [3] .

Publications

  1. Dova Pharmaceuticals. Dova Pharmaceuticals Announces New Drug Application Submission to FDA for Avatrombopag, a Second Generation Thrombopoietin Receptor Agonist. Media-Rel 2017;.

    Media Release
  2. Terrault N, Bibbiani F, Chen Y-C, Izumi N, Kayali Z, Lazcano Soto JR, et al. Superiority of Avatrombopag (AVA) to Placebo (PBO) for the Treatment of Chronic Liver Disease (CLD)-Associated Thrombocytopenia (TCP) in Patients Undergoing Scheduled Proce-dures: Results of 2 Randomized, PBO-Con-trolled Phase 3 Studies. AASLD-2017 2017; abstr. 217.

    Available from: URL: http://onlinelibrary.wiley.com/doi/10.1002/hep.29500/epdf
  3. Saab S, Alkhouri N, Allen LF, Aggarwal K, Vredenburg M, Tian W. Efficacy of Avatrombopag Compared with Placebo Across Various Mean Baseline Platelet Count Subgroups- Pooled Data from 2 Phase 3 Studies. DDW-2018 2018; abstr. Tu1553.

    Available from: URL: https://ep70.eventpilot.us/web/page.php?nav=false&page=IntHtml&project=DDW18&id=2912817&plannersession=true
  4. Sammy S, Alkhouri N, Allen LF, Aggarwal K, Vredenburg M, Tian W, et al. Efficacy of avatrombopag compared with placebo across various mean baseline platelet count subgroups- pooled data from 2 Phase 3 studies. ILC-2018 2018; abstr. SAT-318.

    Available from: URL: http://ilc-congress.eu/
  5. Terrault N, Chen YC, Izumi N, Kayali Z, Mitrut P, Tak WY, et al. Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia. Gastroenterology 2018;.

    PubMed | CrossRef Fulltext
  6. Reau NS, Sammy S, Allen LF, Aggarwal K, Vredenburg M, Kim WR. Avatrombopag decreases need for platelet transfusion in patients chronic liver disease and thrombocytopenia undergoing medical procedures with low to high associated bleeding risks. ILC-2018 2018; abstr. SAT-317.

    Available from: URL: http://ilc-congress.eu/
  7. Nomoto M, Ferry J, Hussein Z. Population Pharmacokinetic/Pharmacodynamic Analyses of Avatrombopag in Patients With Chronic Liver Disease and Optimal Dose Adjustment Guide With Concomitantly Administered CYP3A and CYP2C9 Inhibitors. J-Clin-Pharmacol 2018;.

    PubMed | CrossRef Fulltext
  8. Saab S, Allen LF, Aggarwal K, Vredenburg M, Terrault N. Consistent Efficacy of Avatrombopag Compared to Placebo in Patients with Thrombocytopenia and Chronic Liver Disease Undergoing Procedures Across Various Liver Disease Severities and Etiologies. DDW-2018 2018; abstr. Tu1548.

    Available from: URL: https://ep70.eventpilot.us/web/page.php?nav=false&page=IntHtml&project=DDW18&id=2913002&plannersession=true
  9. Sammy S, Allen LF, Aggarwal K, Vredenburg M, Terrault N. Consistent efficacy of avatrombopag compared to placebo in patients with thrombocytopenia and chronic liver disease undergoing procedures across various disease severities and etiologies. ILC-2018 2018; abstr. SAT-319.

    Available from: URL: http://ilc-congress.eu/
  10. Dova Pharmaceuticals. Dova Pharmaceuticals Announces U.S. FDA Approval of DOPTELET(R)(avatrombopag). Media-Rel 2018;.

    Media Release
  11. Frelinger III AL, Koganov ES, Forde EE, Carmichael SL, Michelson AD. Avatrombopag, a Novel Thrombopoietin Receptor Agonist, Increases Platelet Counts without Increasing Platelet Activation in Patients with Thrombocytopenia Due to Chronic Liver Disease. ASH-Hem-2017 2017; abstr. 290.

    Available from: URL: https://ash.confex.com/ash/2017/webprogram/Paper104502.html
  12. Poordad F, Vredenburg M, Allen LF, Aggarwal K, Alkhouri N. Superiority of Avatrombopag to Placebo in Increasing Platelet Counts and Reducing Platelet Transfusions in Patients with Chronic Liver Disease-Associated Thrombocytopenia Undergoing Scheduled Procedures- Pooled Analysis of 2 Randomized Phase 3 Studies. DDW-2018 2018; abstr. Su1468.

    Available from: URL: https://ep70.eventpilot.us/web/page.php?nav=false&page=IntHtml&project=DDW18&id=2912956&plannersession=true
  13. Michelson AD, Smolensky Koganov E, Forde EE, Carmichael SL, Frelinger AL 3rd. Avatrombopag Increases Platelet Count but Not Platelet Activation in Patients with Thrombocytopenia due to Liver Disease. J-Thromb-Haemost 2018;.

    PubMed | CrossRef Fulltext
  14. Caldwell S, Alkhouri N, Allen LF, Aggarwal K, Vredenburg M, Tian W, et al. Characterization of Baseline Thrombopoietin Levels in Patients With Chronic Liver Disease: Results From 2 Pooled Clinical Studies in Patients With Thrombocytopenia and Liver Disease. ACG-2018 2018; abstr. P0606.

    Available from: URL: https://www.eventscribe.com/2018/ACG/ajaxcalls/PosterInfo.asp?efp=RFNSWFFHSFY2NDI0&PosterID=163067&rnd=0.7672061
  15. Poordad F, Allen LF, Aggarwal K, Vredenburg M, Alkhouri N. Superiority of Avatrombopag to Placebo in I Reducing Platelet Transfusions in Patients with Thrombocytopenia and Chronic Liver Disease Undergoing Scheduled Procedures- Pooled Analysis of 2 Studies. EHA-2018 2018; abstr. PS1401.

    Available from: URL: https://learningcenter.ehaweb.org/eha/2018/stockholm/215691/kavita.aggarwal.superiority.of.avatrombopag.to.placebo.in.i.reducing.platelet.html?f=menu=6*ce_id=1346*ot_id=19068*media=3*marker=167
  16. Terrault N, Kuter DJ, Izumi N, Kayali Z, Mitrut P, Tak WY, et al. Superiority of Avatrombopag to Placebo in Increasing Platelet Counts in Patients with Chronic Liver Disease-Associated Thrombocytopenia Undergoing Scheduled Procedures: Results from 2, Phase 3 Randomized Studies. ASH-Hem-2017 2017; abstr. 18.

    Available from: URL: https://ash.confex.com/ash/2017/webprogram/Paper105516.html
  17. Vredenburg M, Reau N, Allen LF, Aggarwal K, Poordad F. Consistent Efficacy of Avatrombopag over Placebo in the Treatment of Thrombocytopenia in Patients with Chronic Liver Disease Undergoing Invasive Procedures Across Demographic Subgroups - Pooled Results of Two Phase 3 Studies. DDW-2018 2018; abstr. Su1475.

    Available from: URL: https://ep70.eventpilot.us/web/page.php?nav=false&page=IntHtml&project=DDW18&id=2913068&plannersession=true

Authors

Author Total Publications First Author Last Author
Aggarwal K 9 - -
Alkhouri N 5 - 2
Allen LF 10 - -
Bibbiani F 2 - 1
Caldwell S 1 1 -
Carmichael SL 2 - -
Chen Y-C 1 - -
Chen YC 1 - -
Dova Pharmaceuticals 2 2 2
Ferry J 1 - -
Forde EE 2 - -
Frelinger AL 3rd 1 - 1
Frelinger III AL 1 1 -
Hassanein T 1 - 1
Hassanein TI 1 - 1
Hussein Z 1 - 1
Izumi N 3 - -
Kayali Z 3 - -
Kim WR 1 - 1
Koganov ES 1 - -
Kuter DJ 1 - -
Lazcano Soto JR 1 - -
Michelson AD 2 1 1
Mitrut P 3 - -
Nomoto M 1 1 -
Poordad F 3 2 1
Reau N 1 - -
Reau NS 1 1 -
Saab S 2 2 -
Sammy S 3 2 -
Shah N 1 - 1
Smolensky Koganov E 1 - -
Tak WY 3 - -
Terrault N 6 3 3
Tian W 3 - 1
Vredenburg M 9 1 -

Trial Centres

Centres

Centre Name Location Trial Centre Country
- Adelaide, South Australia Australia
- Amiens cedex 1, Somme France
- Bangkoknoi, Bangkok Thailand
- Barcelona Spain
- Bari Italy
- Bedford Park, South Australia Australia
- Beijing China
- Bekescsaba Hungary
- Bologna Italy
- Bruxelles Belgium
- Budapest Hungary
- Busan South-Korea
- Camperdown, New South Wales Australia
- Changsha, Hunan China
- Chuncheon-si, Gangwon-do South-Korea
- Ciudad Autonoma Buenos Aires Argentina
- Clermont Ferrand cedex 1, Puy de Dome France
- Coimbra Portugal
- Daegu South-Korea
- Dallas, Texas USA
- Dunaujvaros Hungary
- Freiburg, Baden Wuerttemberg Germany
- Genova Italy
- Grenoble cedex 9, Isere France
- Guri-si, Gyeonggi-do South-Korea
- Gyula Hungary
- Hamburg Germany
- Harlingen, Texas USA
- Herne, Nordrhein Westfalen Germany
- Houston, Texas USA
- Hwasun-gun, Jeollanam-do South-Korea
- Incheon South-Korea
- Jackson, Mississippi USA
- Jacksonville, Florida USA
- Kaohsiung Taiwan
- Kaohsiung City Taiwan
- Kaposvar Hungary
- Katowice Poland
- Kecskemet Hungary
- Kiel, Schleswig Holstein Germany
- Klong Luang, Pathumthani Thailand
- Koeln, Nordrhein Westfalen Germany
- La Serena Chile
- Lancaster, California USA
- Leeds, West Yorkshire United-Kingdom
- Leuven Belgium
- Linz Austria
- Lisboa Portugal
- Lodz Poland
- London, Greater London United-Kingdom
- London, Ontario Canada
- Long Beach, California USA
- Los Angeles, California USA
- Manchester, Greater Manchester United-Kingdom
- Mendoza Argentina
- Milano Italy
- Minneapolis, Minnesota USA
- Modena Italy
- Muang, Chiang Mai Thailand
- Myslowice Poland
- Nanjing, Jiangsu China
- New Orleans, Louisiana USA
- New York, New York USA
- Palermo Italy
- Palmetto Bay, Florida USA
- Philadelphia, Pennsylvania USA
- Pilar, Buenos Aires Argentina
- Pittsburgh, Pennsylvania USA
- Pontevedra Spain
- Porto Portugal
- Porto Alegre, Rio Grande do Sul Brazil
- Ratchathewi, Bangkok Thailand
- Reims, Marne France
- Rochester, Michigan USA
- Sacramento, California USA
- San Antonio, Texas USA
- San Bernardino, California USA
- San Francisco, California USA
- San Giovanni Rotondo, Foggia Italy
- Santiago Chile
- Sao Jose do Rio Preto, Sao Paulo Brazil
- Sao Paulo Brazil
- Seongnam-Si, Gyeonggi-do South-Korea
- Seoul South-Korea
- Sevilla Spain
- Shanghai, Shanghai China
- Strasbourg, Bas Rhin France
- Suwon, Gyeonggi-do South-Korea
- Szczecin Poland
- Szombathely Hungary
- Taichung City Taiwan
- Tainan city Taiwan
- Taipei Taiwan
- Taipei city Taiwan
- Tampa, Florida USA
- Taoyuan City Taiwan
- The Bronx, New York USA
- Toronto, Ontario Canada
- Truro, Cornwall United-Kingdom
- Udine Italy
- Valencia Spain
- Valladolid Spain
- Vandoeuvre les Nancy France
- Viana do Castelo Portugal
- Vienna Austria
- Vila Real Portugal
- Viseu Portugal
- Wien Austria
- Wolverhampton, West Midlands United-Kingdom
- Wroclaw Poland
- Yangsan-si, Gyeongnam South-Korea
- Zalaegerszeg Hungary
Eisai Inc
Telephone number +4408456761400
Fax number +4408456761401
LmedInfo@eisai.net
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Eisai Inc
Telephone number +4408456761400
Fax number +4408456761401
LmedInfo@eisai.net
show details
Hatfield United-Kingdom
Eisai Incorporation
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USA

Trial History

Event Date Event Type Comment
10 Oct 2018 Results Results presented at the American College of Gastroenterology Annual Scientific Meeting and Postgraduate Course 2018 Updated 05 Nov 2018
28 Sep 2018 Results Results from ADAPT 1 and ADAPT 2 studies published in the Journal of Thrombosis and Haemostasis Updated 21 Nov 2018
09 Aug 2018 Other trial event Mexico was a planned locations for this study. Updated 21 Aug 2018
17 Jun 2018 Results Results of a pooled analysis from ADAPT-1 and ADAPT-2 trials (n=435) presented at the 23rd Congress of the European Haematology Association Updated 20 Jul 2018
15 Jun 2018 Results Results of pooled data from 14 trials, were published in the Journal of Clinical Pharmacology. Updated 11 Jul 2018
05 Jun 2018 Results Results evaluating the efficacy of Avatrombopag compared to placebo (PBO) in increasing platelet counts (PC) and reducing the need for platelet transfusion from two randomized trials (ADAPT-1 and ADAPT-2) presented at the Digestive Disease Week 2018 Updated 19 Jul 2018
05 Jun 2018 Results Results of pooled analysis of 2 randomized phase 3 studies (ADAPT-1 and ADAPT-2) presented at the Digestive Disease Week 2018 Updated 17 Jul 2018
05 Jun 2018 Results Pooled subgroup analysis results of ADAPT-1 and ADAPT-2 trials evaluating the efficacy of AVA in increasing platelet count (PC) in various subgroups based on their pre-treatment PC at baseline presented at the Digestive Disease Week 2018 Updated 16 Jul 2018
05 Jun 2018 Results Pooled subgroup analysis results of ADAPT-1 and ADAPT-2 evaluating the efficacy of AVA compared to placebo in various patient subgroups presented at the Digestive Disease Week 2018 Updated 16 Jul 2018
04 Jun 2018 Other trial event Data from ADAPT-1 and ADAPT-2 trials will be presented at the 23rd Congress of the European Hematology Association (EHA) 2018 meeting, according to a Dova Pharmaceuticals media release. Updated 08 Jun 2018
04 Jun 2018 Other trial event Pooled data from ADAPT-1 and ADAPT-2 trials will be presented at the Digestive Disease Week (DDW) 2018 meeting, according to a Dova Pharmaceuticals media release. Updated 08 Jun 2018
04 Jun 2018 Other trial event Data from ADAPT-1 and ADAPT-2 trials will be presented at 64th International Society on Thrombosis and Haemostasis (ISTH) Annual Scientific and Standardization Committee (SSC) Meeting 2018, according to a Dova Pharmaceuticals media release. Updated 08 Jun 2018
21 May 2018 Results Results presented in the Dova Pharmaceuticals media release. Updated 28 May 2018
21 May 2018 Other trial event According to a Food and Drug Administration media release, based on the data from ADAPT-1 and ADAPT-2 trials, the U.S. Food and Drug Administration has approved Doptelet (avatrombopag) tablets to treat low blood platelet count (thrombocytopenia) in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure. Updated 28 May 2018
17 May 2018 Results Results of ADAPT-1 and ADAPT-2 studies, published in the Gastroenterology Updated 24 May 2018
14 Apr 2018 Results Results of a pooled analysis from ADAPT-1 and ADAPT-2 studies, apresented at The International Liver Congress 2018. Updated 16 May 2018
14 Apr 2018 Results Results of a pooled analysis from ADAPT-1 and ADAPT-2 studies, apresented at The International Liver Congress 2018. Updated 16 May 2018
14 Apr 2018 Results Results of a pooled analysis from ADAPT-1 and ADAPT-2 studies, apresented at The International Liver Congress 2018. Updated 16 May 2018
28 Feb 2018 Other trial event Last checked against the ClinicalTrials. gov record. Updated 28 Feb 2018
16 Feb 2018 Other trial event Last checked against European Clinical Trials Database record. Updated 16 Feb 2018
12 Dec 2017 Results Results of association of increase of platelet counts without increasing platelet activation by using data from two studies including this study presented at the 59th Annual Meeting and Exposition of the American Society of Hematology. Updated 28 Dec 2017
12 Dec 2017 Results Results of ADAPT 1 and ADAPT 2 studies assessing superiority of Avatrombopag to placebo, presented at the 59th Annual Meeting and Exposition of the American Society of Hematology. Updated 22 Dec 2017
04 Dec 2017 Other trial event According to a Dova Pharmaceuticals media release, data from the study will be presented at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition. Updated 06 Dec 2017
27 Nov 2017 Other trial event According to a Dova Pharmaceuticals media release, the NDA for avatrombopag has been accepted for filing and has been granted Priority Review by the United States Food and Drug Administration (FDA). The submission is based on ADAPT 1 and ADAPT 2 trials. The Prescription Drug User Fee Act (PDUFA) goal date for an FDA decision is May 21, 2018. Updated 29 Nov 2017
24 Oct 2017 Results Results from ADAPT 1 and ADAPT 2 studies, presented at The Liver Meeting 2017: 68th Annual Meeting of the American Association for the Study of Liver Diseases Updated 17 Nov 2017
22 Sep 2017 Results Results published in a Dova Pharmaceuticals media release. Updated 26 Sep 2017
22 Sep 2017 Endpoint met Primary endpoint has been met. (The proportion of participants who require platelet transfusion or rescue therapy for bleed after randomization and up to 7 days after the elective procedure), according to a Dova Pharmaceuticals media release. Updated 26 Sep 2017
22 Sep 2017 Other trial event According to a Dova Pharmaceuticals media release, based on the data from ADAPT-1 and ADAPT-2 trials the company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for avatrombopag, for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) who are scheduled to undergo a procedure. Updated 26 Sep 2017
10 Aug 2017 Other trial event According to a Dova Pharmaceuticals media release, data from ADAPT-1 and ADAPT-2 trials has been accepted for presentation at the American Association for the Study of Liver Disease Annual Meeting Updated 16 Aug 2017
18 Apr 2017 Status change - completed Status changed from active, no longer recruiting to completed, as per ClinicalTrials. gov record. Updated 08 May 2017
06 Jan 2017 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting, as per a Dova Pharmaceuticals media release. Updated 08 May 2017
19 May 2016 Other trial event According to a PBM media release, this phase III study is conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration as a potential treatment for thrombocytopenia in patients with chronic liver disease undergoing an elective procedure. Updated 25 May 2016
02 Nov 2015 Completion date Planned End Date changed from 1 Aug 2015 to 1 Dec 2016 as reported by ClinicalTrials. gov record. Updated 05 Nov 2015
02 Nov 2015 Other trial event Planned primary completion date changed from 1 Jul 2015 to 1 Dec 2016 as reported by ClinicalTrials. gov record. Updated 05 Nov 2015
17 Dec 2014 Other trial event According to the ClinicalTrials.gov record, planned primary completion date changed from 1 May 2015 to 1 Jul 2015. Updated 31 Dec 2014
02 Jul 2014 Other trial event New source identified and integrated (Mayo Clinic; IRB13-008902). Updated 02 Jul 2014
27 May 2014 Other trial event New source identified and integrated (European Clinical Trials Database; EudraCT2013-000965-34). Updated 27 May 2014
31 Mar 2014 Status change - recruiting Status changed from not yet recruiting to recruiting, as per ClinicalTrials. gov record. Updated 27 May 2014
16 Jan 2014 Other trial event Planned initiation date changed from 1 Nov 2013 to 1 Jan 2014 as reported by ClinicalTrials.gov record. Updated 20 Feb 2014
09 Nov 2013 New trial record New trial record Updated 09 Nov 2013

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