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Trial record 71 of 10870 for:    Placebo AND once

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once-daily Oral Avatrombopag in Japanese Subjects With Chronic Liver Diseases and Thrombocytopenia

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ClinicalTrials.gov Identifier: NCT02227693
Recruitment Status : Completed
First Posted : August 28, 2014
Results First Posted : February 28, 2019
Last Update Posted : February 28, 2019
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )

Tracking Information
First Submitted Date  ICMJE August 26, 2014
First Posted Date  ICMJE August 28, 2014
Results First Submitted Date  ICMJE December 4, 2017
Results First Posted Date  ICMJE February 28, 2019
Last Update Posted Date February 28, 2019
Actual Study Start Date  ICMJE July 2014
Actual Primary Completion Date April 1, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
Percentage of Participants With Platelet Count Greater Than or Equal to 50 x 10^9/L and at Least 20 x 10^9/L Increase From Baseline at Visit 4 [ Time Frame: Baseline and Visit 4 (Day 10) ]
Responders were defined as participants whose platelet count was greater than or equal to 50×10^9/liter (L) and change from baseline was at least 20×10^9/L at Visit 4. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis. Two-sided 95% confidence interval (CI) is calculated by Clopper and Pearson method.
Original Primary Outcome Measures  ICMJE
 (submitted: August 26, 2014)
Proportion of subjects who had a platelet count greater than or equal to 50 x 10^9/L and at least 20 x 10^9/L increase from baseline at Visit 4 [ Time Frame: Baseline and Visit 4 ]
Change History Complete list of historical versions of study NCT02227693 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
  • Percentage of Participants With Platelet Count Greater Than or Equal to 50 x 10^9/L at Each Visit [ Time Frame: Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35) ]
    Responders were defined as the participants whose platelet count greater than or equal to 50 x 10^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis. Two-sided 95% CI is calculated by Clopper and Pearson method.
  • Percentage of Participants With Platelet Count Greater Than or Equal to 75 x 10^9/L at Each Visit [ Time Frame: Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35) ]
    Responders were defined as the participants whose platelet count greater than or equal to 75 x 10^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis. Two-sided 95% CI is calculated by Clopper and Pearson method.
  • Percentage of Participants With Platelet Count Greater Than or Equal to 150 x 10^9/L At Each Visit [ Time Frame: Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35) ]
    Responders were defined as the participants whose platelet count greater than or equal to 150 x 10^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis.
  • Percentage of Participants With Platelet Count Greater Than or Equal to 200 x 10^9/L At Each Visit [ Time Frame: Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35) ]
    Responders were defined as the participants whose platelet count greater than or equal to 200 x 10^9/L by visit. Participants receiving a platelet transfusion prior to the platelet count assessment at Visit 4 were considered as non-responders in the analysis.
  • Platelet Count and Change From Baseline in Platelet Count by Visit [ Time Frame: Baseline, Visit 3 (Day 4 or 5), Visit 4 (Day 10), Visit 5 (Day 17) and Visit 6 (Day 35) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2014)
  • Proportion of subjects who had a platelet count greater than or equal to 50 x 10^9/L, greater than or equal to 75 x 10^9/L, greater than or equal to 150 x 10^9/L, or greater than or equal to 200 x 10^9/L at each visit [ Time Frame: Baseline and at Each Visit until last observation carried forward (LOCF) ]
  • Change from baseline in platelet count [ Time Frame: Baseline and at Each Visit until last observation carried forward (LOCF) ]
  • Safety and tolerability of avatrombopag as a measure of Adverse Events [ Time Frame: Up to Day 35 ]
    All adverse events (AEs) and serious adverse events (SAEs) will be measured
  • Safety and tolerability of avatrombopag as a measure of laboratory evaluation for hematology [ Time Frame: Up to 14 months ]
  • Safety and tolerability of avatrombopag as a measure of laboratory evaluation for serum [ Time Frame: Up to 14 months ]
  • Safety and tolerability of avatrombopag as a measure of laboratory evaluation for urine [ Time Frame: Up to 14 months ]
  • Safety and tolerability of avatrombopag as a measure of vital signs [ Time Frame: Up to 14 months ]
  • Safety and tolerability of avatrombopag as a measure of ECG [ Time Frame: Up to 14 months ]
Current Other Pre-specified Outcome Measures
 (submitted: October 17, 2018)
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From the date of first dose of study drug up to 30 days after the last dose of the study drug, up to approximately 10 months ]
    Safety assessments consisted of monitoring and recording all AEs and SAEs, regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms; 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. A treatment-emergent adverse event (TEAE) was 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. For each category, a participant with two or more adverse events in that category was counted only once. Treatment-related TEAEs were considered by the investigator to be possibly or probably related to study drug or TEAEs with a missing causality.
  • Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Value (TEMAV) for Haematology [ Time Frame: From the date of Screening until the date of last dose of study drug plus 30 days (Approximately 10 months) ]
  • Number of Participants With Clinically Significant Findings in Laboratory Values for Serum [ Time Frame: From the date of Screening until the date of last dose of study drug plus 30 days (Approximately 10 months) ]
  • Number of Participants With Clinically Significant Findings in Laboratory Values for Urinalysis [ Time Frame: From the date of Screening until the date of last dose of study drug plus 30 days (Approximately 10 months) ]
  • Number of Participants With Clinically Significant Change From Baseline in Vital Sign Values [ Time Frame: From the date of Screening until the date of last dose of study drug plus 30 days (Approximately 10 months) ]
  • Number of Participants With Markedly Abnormal Electrocardiographs [ Time Frame: From the date of Screening until the date of last dose of study drug plus 30 days (Approximately 10 months) ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once-daily Oral Avatrombopag in Japanese Subjects With Chronic Liver Diseases and Thrombocytopenia
Official Title  ICMJE A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once-daily Oral Avatrombopag in Japanese Subjects With Chronic Liver Disease and Thrombocytopenia
Brief Summary This is a phase 2, randomized, double-blind, placebo-controlled, parallel group study using avatrombopag for Japanese subjects with thrombocytopenia associated with chronic liver disease. This study will assess the effect of avatrombopag on platelet counts in Japanese subjects. Subjects will be enrolled into 2 cohorts according to the mean platelet count measured at Screening and Baseline. Within the lower baseline platelet count cohort (less than 40 x 10^9/L), subjects will be randomized in a 1:1:1:3 ratio to receive placebo, 20 mg avatrombopag, 40 mg avatrombopag, or 60 mg avatrombopag for 5 days. Within the higher baseline platelet count cohort (from 40 to less than 50 x 10^9/L), subjects will be randomized in a 2:1:2 ratio to receive placebo, 20 mg avatrombopag, or 40 mg avatrombopag for 5 days.
Detailed Description

This study will consist of Prerandomization Phase and Randomization Phase. The Prerandomization Phase includes a Screening Period (Day -28 to Day -1) and a Baseline Period (Day 1). During the Prerandomization Phase, participants will be divided into two cohorts based on the platelet count: Low Platelet Count Cohort and High Platelet Count Cohort. Participants in Low Platelet Count Cohort will be randomized to receive one of the four treatments: Placebo, Avatrombopag 20 mg, Avatrombopag 40 mg, or Avatrombopag 60 mg. Participants in High Platelet Count Cohort will be randomized to receive one of the three treatments: Placebo, Avatrombopag 20 mg, or Avatrombopag 40 mg.

The Randomization Phase includes the Treatment Period and the Follow-up Period. The Follow-up Period comprises 3 visits: Visit 4 (5 to 8 days after last dose of study drug [Study Day 10 to 13]), Visit 5 (12 to 15 days after last dose of study drug [Study Day 17 to 20]), and 30 days after receiving the last dose of study drug.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Thrombocytopenia Associated With Chronic Liver Disease
Intervention  ICMJE
  • Drug: avatrombopag
    E5501 (avatrombopag) 20-mg tablets
  • Drug: Placebo
    Placebo matching 20-mg tablets
Study Arms  ICMJE
  • Experimental: avatrombopag 20-mg
    20 mg avatrombopag (1 x 20 mg tablet and 2 x 20 mg matching placebo tablets) once daily on Days 1 through 5
    Intervention: Drug: avatrombopag
  • Experimental: avatrombopag 40-mg
    40 mg avatrombopag (2 x 20 mg tablets and 1 x 20 mg matching placebo tablet) once daily on Days 1 through 5
    Intervention: Drug: avatrombopag
  • Experimental: avatrombopag 60-mg
    60 mg avatrombopag (3 x 20 mg tablets) once daily on Days 1 through 5
    Intervention: Drug: avatrombopag
  • Placebo Comparator: placebo l
    Placebo (3 x 20-mg matching placebo tablets) once daily on Days 1 through 5
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 19, 2015)
39
Original Estimated Enrollment  ICMJE
 (submitted: August 26, 2014)
33
Actual Study Completion Date  ICMJE April 1, 2015
Actual Primary Completion Date April 1, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Japanese subjects greater than or equal to 20 years of age at Screening with chronic liver disease.
  2. Subjects who have a mean baseline platelet count of less than 50 x 10^9/L. Platelet counts will 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.
  3. Model For End-stage Liver Disease (MELD) score 24 at Screening.
  4. If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be stable for 7 days prior to Screening.
  5. Provide written informed consent.
  6. Willing and able to comply with all aspects of the protocol.

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 less than 10 cm/second at Screening.
  4. Hepatic encephalopathy that cannot be effectively treated.
  5. Subjects 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. Known to be human immunodeficiency virus positive.
  14. Any clinically significant acute or active bleeding (eg, gastrointestinal, central nervous system).
  15. Known history of any primary hematologic disorder (eg, immune thrombocytopenic purpura, myelodysplastic syndrome).
  16. Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency etc.)
  17. Subjects 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).
  18. 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 subject 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.
  19. 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.
  20. Post liver transplant subjects.
  21. Any subject who has previously received avatrombopag.
  22. Hypersensitivity to avatrombopag maleate or any of its excipients.
  23. Hemoglobin levels less than or equal to 8.0 or greater than or equal to 16.0 g/dL at Screening.
  24. White blood cell count less than or equal to 1.5 x 10^9/L or greater than or equal to 15.0 x 10^9/L at Screening.
  25. Serum sodium level less than or equal to 130 milliequivalents/L at Screening.
  26. Current malignancy including solid tumors and hematologic malignancies (except HCC).
  27. Any history of a medical condition or a concomitant medical condition that, in the opinion of the investigator(s), would compromise the subject's ability to safely complete the study.
  28. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days of Screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02227693
Other Study ID Numbers  ICMJE E5501-J081-204
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eisai Inc. ( Eisai Co., Ltd. )
Study Sponsor  ICMJE Eisai Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Eisai Inc.
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP