Thrombocytopenia Related to Chronic Liver Disease Clinical Trial
Official title:
A Phase 2, Randomized, Multicenter, Placebo-Controlled, Double-Blind, Parallel-Group Study to Evaluate the Efficacy, Safety, and Population Pharmacokinetics of Once-Daily Oral E5501 Tablets Used Up to 7 Days in Subjects With Chronic Liver Diseases and Thrombocytopenia Prior to Elective Surgical or Diagnostic Procedures
| Verified date | January 2018 |
| Source | Eisai Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this study is to evaluate the efficacy of once-daily Oral avatrombopagin subjects with chronic liver diseases and thrombocytopenia prior to elective surgical or diagnostic procedures, to evaluate the safety of short-term administration of avatrombopag and to evaluate the pharmacokinetics (PK) of E5501.
| Status | Completed |
| Enrollment | 130 |
| Est. completion date | December 21, 2011 |
| Est. primary completion date | November 11, 2011 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Key Inclusion Criteria: 1. Males or females = 18 years of age 2. Thrombocytopenia (defined as a platelet count = 10,000 - = 50,000 (+15%)/mm^3 ) 3. Model for End-Stage Liver Disease (MELD) scores = 24 4. Chronic liver diseases due to one of the following three etiologies: Chronic Viral Hepatitis from one of the following categories - Chronic Hepatitis C (defined as the presence of anti-hepatitis C virus [HCV] antibodies and/or detectable serum HCV ribonucleic acid [RNA] levels) - OR chronic Hepatitis B (defined as the presence of hepatitis B surface antigen [HBsAg] and/or detectable serum hepatitis B virus [HBV] deoxyribonucleic acid [DNA]) - OR chronic Hepatitis B and C co-infection (as defined by the above bullet points) - OR chronic Hepatitis C and history of alcohol abuse - OR chronic Hepatitis B and history of alcohol abuse NASH diagnosed as: - absence of serologic evidence of viral hepatitis and - convincing evidence of a history of minimal or no alcohol consumption, and - histologic picture of steatohepatitis OR - when histology is unavailable, then clinical, radiographic and laboratory evidence of NASH Alcoholic liver disease diagnosed as: - absence of serologic evidence of viral hepatitis and - history of heavy alcohol consumption and - histologic picture of alcoholic liver disease OR - when histology is unavailable, then clinical, radiographic and laboratory evidence of hepatitis combined with years of excessive alcohol intake 5. Subjects who are scheduled to undergo an elective invasive procedure between 1 to 4 days post last dose of study drug. 6. Adequate renal function as evidenced by a calculated creatinine clearance =50 mL/minute per the Cockcroft and Gault formula 7. Life expectancy =3 months Key Exclusion Criteria: 1. Hepatic encephalopathy that cannot be effectively treated. 2. Platelet transfusion within 7 days prior to the first dose of study drug 3. Received blood products, eg, FFP and cryoprecipitate 7 days prior to the first dose of study drug 4. Have surgical or diagnostic procedure scheduled during the Randomization Phase (Day 1 to Day 8) of this study 5. Interferon use within 2 weeks of Day 1 6. Hormonal contraceptive use within 60 days of study entry 7. History of human immunodeficiency virus (HIV) infection 8. Any prohibited concomitant medications or therapy that cannot be discontinued by Visit 1 9. Active alcohol abuse, active alcohol dependence syndrome, drug abuse, or drug dependence within 6 months of the study start (unless participating in a controlled rehabilitation program) 10. Acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of the study start 11. History of any primary hematologic disorder 12. History of arterial or venous thrombosis, including thrombosis of any part of the splenic-mesenteric system 13. Any evidence of current portal vein thrombosis (PVT) as detected by Doppler sonography or appropriate MRI/CT imaging at Screening and/or within approximately 30 days prior to Screening 14. Any acute/active bleeding (gastrointestinal [GI], central nervous system [CNS], etc) 15. Uncompensated congestive heart failure (New York Heart Association [NYHA] Class III or IV) 16. Pre-diagnosed Immune Thrombocytopenic Purpura (ITP) 17. History of Myelodysplastic Syndrome (MDS) 18. Females who are pregnant (positive ß-hCG test ) or breastfeeding 19. Current use of recreational drugs 20. Post-transplant patients 21. Subjects who have participated in another investigational trial within 30 days prior to Visit 1. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Ochsner Clinic Foundation | New Orleans | Louisiana |
| Lead Sponsor | Collaborator |
|---|---|
| Eisai Inc. |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of Participants Experiencing Response | Platelet counts (PC) were determined from blood draws. A responder is defined as a participant having an increase of at least 20,000/mm^3 PC from Baseline and a PC greater than 50,000/mm^3 at least once during Day 4 through Day 8. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (end of treatment (EOT)), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used. | Day 8 (Visit 5, EOT) | |
| Secondary | Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline | Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used. | Day 8 (Visit 5, EOT) | |
| Secondary | Percentage of Participants Experiencing Dose-response by Visit | Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used. | Day 4 (Visit 3), Day 6 ( Visit 4), Day 8 (Visit 5, EOT), 3 Day Post Last Dose (Visit 6), and 7 Day Post Last Dose (Visit 7) | |
| Secondary | Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4 | Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used. | Day 4 (Visit 3) | |
| Secondary | Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8 | Platelet counts were determined from blood draws. Missing PC assessments at any given time point was considered to be a non-response at that point and were not estimated. For PC measurements taken after the last dose day (EOT), the postdose windows applied. If there was more than one PC within the same analysis visit window, the following selection rules were applied sequentially to determine which PC was used for that time point: 1) the PC that was closer to the target date was used, 2) if PC were equal-distance in days from the target day, the later one based on measurement date and time was used, and 3) if there was more than one PC on the same day, if it was a baseline record, the largest one was used; if it was a postbaseline record, the smallest one was used. | Day 4 (Visit 3) and Day 8 (Visit 5, EOT) |