Thrombocytopenia Related to Chronic Liver DiseasePhase 2NCT00914927
Once-Daily Oral Avatrombopag Tablets Used in Subjects With Chronic Liver Diseases and Thrombocytopenia Prior to Elective Surgical or Diagnostic Procedures
A Phase 2 study testing Avatrombopag in people with Thrombocytopenia Related to Chronic Liver Disease, run by Eisai Inc. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thrombocytopenia Related to Chronic Liver Disease
- What is being tested?
- Avatrombopag
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to 21 Dec 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females ≥ 18 years of age
- Thrombocytopenia (defined as a platelet count ≥ 10,000 - ≤ 50,000 (+15%)/mm^3 )
- Model for End-Stage Liver Disease (MELD) scores ≤ 24
- 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)
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- 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
- Subjects who are scheduled to undergo an elective invasive procedure between 1 to 4 days post last dose of study drug.
- Adequate renal function as evidenced by a calculated creatinine clearance ≥50 mL/minute per the Cockcroft and Gault formula
- Life expectancy ≥3 months
Who cannot join
- Hepatic encephalopathy that cannot be effectively treated.
- Platelet transfusion within 7 days prior to the first dose of study drug
- Received blood products, eg, FFP and cryoprecipitate 7 days prior to the first dose of study drug
- Have surgical or diagnostic procedure scheduled during the Randomization Phase (Day 1 to Day 8) of this study
- Interferon use within 2 weeks of Day 1
- Hormonal contraceptive use within 60 days of study entry
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- History of human immunodeficiency virus (HIV) infection
- Any prohibited concomitant medications or therapy that cannot be discontinued by Visit 1
- 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)
- Acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of the study start
- History of any primary hematologic disorder
- History of arterial or venous thrombosis, including thrombosis of any part of the splenic-mesenteric system
- 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
- Any acute/active bleeding (gastrointestinal [GI], central nervous system [CNS], etc)
- Uncompensated congestive heart failure (New York Heart Association [NYHA] Class III or IV)
- Pre-diagnosed Immune Thrombocytopenic Purpura (ITP)
- History of Myelodysplastic Syndrome (MDS)
- Females who are pregnant (positive β-hCG test ) or breastfeeding
- Current use of recreational drugs
- Post-transplant patients
- Subjects who have participated in another investigational trial within 30 days prior to Visit 1.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
About this study
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
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.
- Being tested
- Avatrombopag, Placebo
- Keywords
- Thrombocytopenia, chronic liver disease
- Medical subject headings
- Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvatrombopagDrug
Avatrombopag first Dose 80 mg followed by 10 mg a day for up to 6 additional days
AvatrombopagDrug
Avatrombopag first Dose 80 mg followed by 20 mg a day for 3 days and then Placebo for 3 additional days
PlaceboDrug
Placebo or inactive substance once a day for up to 7 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Avatrombopag |
| 2 | Experimental | Not described Receives: Drug: Avatrombopag; Drug: Placebo |
| 3 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 8 (Visit 5, EOT)
Secondary outcomes (4)
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.
Measured: Day 8 (Visit 5, EOT)
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.
Measured: 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)
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.
Measured: Day 4 (Visit 3)
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.
Measured: Day 4 (Visit 3) and Day 8 (Visit 5, EOT)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2009 (estimated)
- Study startMay 2009
- Primary completion11 Nov 2011
- Study completion21 Dec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Thrombocytopenia Related to Chronic Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tim Jenkins, Study director, Eisai Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00914927
- Sponsor's protocol ID
- E5501-G000-202
- Status last verified
- Jan 2018
- First submitted
- 4 Jun 2009
- Last updated
- 23 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00914927
- Acronym / sponsor ID
- E5501-G000-202
- Keywords
- Thrombocytopenia, chronic liver disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- May 2009
- Primary completion
- 11 Nov 2011 (actual)
- Study completion
- 21 Dec 2011 (actual)
- First posted
- 5 Jun 2009 (estimated)
- Results
- Posted 23 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Avatrombopag |
| 2 | Experimental | Drug: Avatrombopag, Drug: Placebo |
| 3 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Males or females ≥ 18 years of age
- Thrombocytopenia (defined as a platelet count ≥ 10,000 - ≤ 50,000 (+15%)/mm^3 )
- Model for End-Stage Liver Disease (MELD) scores ≤ 24
- Chronic liver diseases due to one of the following three etiologies:
- Chronic Viral Hepatitis from one of the following categories
Key exclusion criteria (21 listed)
- Hepatic encephalopathy that cannot be effectively treated.
- Platelet transfusion within 7 days prior to the first dose of study drug
- Received blood products, eg, FFP and cryoprecipitate 7 days prior to the first dose of study drug
- Have surgical or diagnostic procedure scheduled during the Randomization Phase (Day 1 to Day 8) of this study
- Interferon use within 2 weeks of Day 1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvatrombopagAvatrombopag first Dose 80 mg followed by 10 mg a day for up to 6 additional days | Drug | 1 |
| AvatrombopagAvatrombopag first Dose 80 mg followed by 20 mg a day for 3 days and then Placebo for 3 additional days | Drug | 2 |
| PlaceboPlacebo or inactive substance once a day for up to 7 days | Drug | 2, 3 |
Primary outcome
Percentage of Participants Experiencing Response
Time frame: Day 8 (Visit 5, EOT)
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.
4 secondary outcomes
Change in Platelet Count on Day 8 (Visit 5 and/or End of Treatment) From Baseline
Time frame: Day 8 (Visit 5, EOT)
Percentage of Participants Experiencing Dose-response by Visit
Time frame: 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)
Percentage of Participants Who Achieved a Platelet Count Greater Than 75,000/mm^3 on Day 4
Time frame: Day 4 (Visit 3)
Percentage of Participants Who Achieved a Platelet Count Greater Than 100,000/mm^3 on Days 4 and 8
Time frame: Day 4 (Visit 3) and Day 8 (Visit 5, EOT)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim Jenkins study director
Eisai Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avatrombopag in people with Thrombocytopenia Related to Chronic Liver Disease, run by Eisai Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Experiencing Response (time frame: Day 8 (Visit 5, EOT)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2018.