Chronic Hepatitis C Virus Related Thrombocytopenia to Evaluate the Effects of E5501

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01355289
• Collaborator: (none)
• Enrollment: 65
• Locations: 2
• Arms: 5
• Duration (Months): 30
• Patients Per Site: 32.5
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

To evaluate the efficacy of E5501 by measuring platelet response in subjects with chronic hepatitis C virus (HCV)-related thrombocytopenia who require antiviral treatment.

Condition or Disease	Intervention/Treatment	Phase
Thrombocytopenia	Drug: Avatrombopag; Drug: Placebo; Drug: Pegylated interferon (PEG-IFN); Drug: Telaprevir; Drug: Ribavirin	Phase 2

Detailed Description

This study had three phases: Prerandomization (Screening), Randomization (Core Study), and Open-Label Extension (OLE). The Randomization Phase included Treatment Periods A1 and A2 and a Follow-up Period (for those participants not continuing into the OLE phase). The OLE Phase included Treatment Periods B1, B2, and B3 (depending on when a participant entered the OLE), and a Follow-up Period. Participants may have been followed for sustained viral response, if appropriate. In the Core Study (randomization phase) participants were randomized (in a 1:1:1:1 ratio) to receive one of four treatments (placebo or avatrombopag [10mg, 20mg, and 30mg] for up to 21 days. Participants who successfully completed Treatment Period A1, (platelet count >=100x10^9/L) initiated antiviral treatment with pegylated interferon (PEG-IFN) alpha-2a and progressed to Treatment Period A2. Participants with a platelet count

=150x10^9/L initiated antiviral treatment and progressed into Treatment Period B2, study drug was interrupted then eventually restarted at 10 mg daily once their platelet counts returned to acceptable levels. Those who were not considered successful after 21 days in Treatment Phase A1 were withdrawn from the Core Study (Part A) and were eligible to enter the OLE at Treatment Period B1. Participants who chose to not enter the OLE entered into the Follow-up Phase. At the end of Treatment Period A2, eligible participants could enter the OLE at Treatment Period B3. In the OLE Phase, participants entering into Open-label Treatment Period B1 began once-daily treatment with avatrombopag at a dose of 20 mg without titration for up to 21 days. Once the participant's platelet counts were sufficient, they entered Treatment Period B2. Participant's eligible to enter into Treatment Period B2 received avatrombopag and antiviral treatment for 13 weeks. Participants who successfully completed Treatment Period A2 or B2 could continue on antiviral treatment for up to a maximum of 48 weeks (including the 13 weeks in Treatment Periods A2 or B2) and open-label avatrombopag, at the investigator's discretion. In Treatment Period B3, the dose of avatrombopag was allowed to be titrated up or down in accordance with the participant's platelet count response, within the range of a minimum of 5 mg and a maximum of 50 mg. In the Follow-up Period, participants were seen at either a single 30-day follow-up visit or followed for the full 30 days after the last dose of avatrombopag.

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Multicenter, Placebo-Controlled, Double-Blind, Parallel-Group Study, With an Open-Label Extension, to Evaluate the Efficacy, Safety, and Pharmacokinetics of E5501 in Subjects With Chronic Hepatitis C Virus Related Thrombocytopenia Who Are Potential Candidates for Antiviral Treatment
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo (Core Study) Placebo, will be administered orally, once daily for up to 21 days.	Drug: Placebo
Active Comparator: Avatrombopag 10 mg (Core Study) Avatrombopag 10 mg, will be administered orally, once daily, preferably with food for up to 21 days.	Drug: Avatrombopag; Other Names: E5501 Avatrombopag maleate
Active Comparator: Avatrombopag 20 mg (Core Study) Avatrombopag 20 mg, will be administered orally, once daily, preferably with food for up to 21 days.	Drug: Avatrombopag; Other Names: E5501 Avatrombopag maleate ; Drug: Pegylated interferon (PEG-IFN); Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor.; Drug: Telaprevir; Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor; Other Names: Incivek Incivo ; Drug: Ribavirin; Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor; Other Names: Virazole Rebetol Copegus Ribasphere Moderiba dose pack Moderiba
Active Comparator: Avatrombopag 30 mg (Core Study) Avatrombopag 30 mg, will be administered orally, once daily, preferably with food for up to 21 days.	Drug: Avatrombopag; Other Names: E5501 Avatrombopag maleate
Experimental: Avatrombopag (Open-Label Extension) Avatrombopag will be initiated at a dose of 20 mg, once daily in the open-label extension (OLE) period. The avatrombopag dose will be titrated up or down in accordance with the participant's individual response, within the range of a minimum of 5 mg and a maximum of 50 mg for up to 48 weeks.	Drug: Avatrombopag; Other Names: E5501 Avatrombopag maleate ; Drug: Pegylated interferon (PEG-IFN); Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor.; Drug: Telaprevir; Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor; Other Names: Incivek Incivo ; Drug: Ribavirin; Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor; Other Names: Virazole Rebetol Copegus Ribasphere Moderiba dose pack Moderiba

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Achieved Platelet Response (Greater Than or Equal to 100 x 10^9/L) by Day 21 of Treatment Period A1 of Core Study [Baseline to Day 21]

   A responder was defined as a participant having a platelet count of greater than or equal to 100x10^9/L by Day 21 starting from an average baseline platelet count of greater than 20 x 10^9/L to less than or equal to 70 x 10^9/L.

Secondary Outcome Measures

1. Change From Baseline of Local Platelet Count by Visit During Treatment Period A1 of Core Study [Day 7 and Day 14]

   Missing platelet counts were imputed using last observation carried forward (LOCF) approach for subjects who achieved platelet response at prior visits.

2. Number of Participants Who Achieved Platelet Count Greater Than 30 X 10^9/L From Baseline to Day 21 During Treatment Period A1 of Core Study [Baseline to Day 21]

   Blood draws were taken to monitor platelet counts.

3. Number of Participants Who Initiated Antiviral Treatment by Day 21 of Period A1 of Core Study [Baseline to Day 21]

   Blood draws were taken to monitor platelet counts during the first 21 days of study treatment. When a platelet count of greater than or equal to 100 X 10^9/L was attained, antiviral treatment was initiated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males or females greater than or equal to 18 years of age

2. Women of childbearing potential must agree to use a highly effective method of contraception for at least one menstrual cycle prior to starting study drug, throughout the entire study period, and for 30 days after the last dose of study drug

3. Subjects with chronic HCV-related thrombocytopenia (defined as a platelet count greater than or equal to 20x10^{9/L to 70x10}9/L) who require antiviral treatment

4. Chronic HCV infection (defined as the presence of anti-HCV antibodies and detectable serum HCV RNA levels)

5. Model for End-stage Liver disease score greater than or equal to 24

6. Adequate renal function as evidenced by a calculated creatinine clearance greater than or equal to 50 mL/minute per the Cockcroft and Gault formula

7. Life expectancy greater than or equal to 3 months

Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from participation in the study:

1. Any history of arterial or venous thrombosis, including partial or complete thrombosis (e.g., stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), thrombosis (partial or complete) in the main portal vein and portal vein branches, and thrombosis of any part of the splenic-mesenteric system

2. Any evidence of current portal vein thrombosis (PVT) as detected by Doppler sonography and portal vein flow rate less than 15 cm/second at Screening or within 30 days prior to Screening (revised per Amendment 02)

3. Any known family history of hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency)

4. Evidence of myocardial infarction in the last 6 months or uncompensated congestive heart failure (New York Heart Association Class III or IV)

5. Co-infection with human immunodeficiency virus (HIV) or hepatitis B or acute hepatitis C

6. Any prohibited concomitant medications or therapy that cannot be discontinued by Visit 1, e.g., subjects currently receiving interferon who cannot undergo a 4-week washout period prior to Screening, or subjects who receive blood products that affect platelet count within 1 week prior to Screening (revised per Amendment 02)

7. Weekly alcohol intake greater than 21 units (168 g) [male] and greater than 14 units (112 g) [female]

8. Any known medical condition, other than chronic liver disease, that can lead to thrombocytopenia

9. History of hepatocellular carcinoma, metastatic liver cancer, or liver transplantation (revised per Amendment 01) (revised per Amendment 02)

10. History of idiopathic thrombocytopenic Purpura (ITP)

11. History of myelodysplastic syndrome

12. History of pernicious anemia or subjects with vitamin B12 deficiency (defined as less than the lower limit of normal [LLN]) who have not had pernicious anemia excluded as a cause (Added per Amendment 02)

13. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that, in the opinion of the investigator, could affect the subject's safety or study conduct

14. Subjects with a history of suicide attempts

15. Subjects with a history of hospitalization for depression within the past 5 years

16. Subjects with any current severe or poorly controlled psychiatric or seizure disorder

17. Current use of recreational drugs

18. Subjects who have participated in another investigational study within 30 days prior to Visit 1

19. Subjects with hypersensitivity, intolerance, or allergy to E5501 or any anti-HCV therapies or their ingredients

20. Any past or current (revised per Amendment 01) medical condition that, in the opinion of the investigator, would compromise the subject's ability to safely complete the study

21. Scheduled for surgery during the projected course of the study

22. Subjects who have any medical conditions or diseases that would contraindicate treatment with anti-HCV therapy (added per Amendment 01)

23. Subjects who are currently treated with proton pump inhibitors (PPIs) or H2-antagonist therapy but have not been receiving a stable dose for at least 6 weeks prior to randomization or have not completed these therapies more than 2 weeks prior to randomization (added per Amendment 01)

24. Fasting gastrin-17 blood levels exceeding 1.5 times the upper limit of normal (ULN) at Screening (including subjects on PPIs or H2 antagonists) (revised per Amendment 02)

25. Subjects with a history of gastric atrophy (added per Amendment 02)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Health Care Consultants	Los Angeles	California	United States
2	Metropolitan Research	Fairfax	Virginia	United States	22031

Sponsors and Collaborators

• Eisai Inc.

Investigators

• Study Director: Alireza Manhuchehri, Eisai Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT01355289
• Other Study ID Numbers: E5501-G000-203
• First Posted: May 18, 2011
• Last Update Posted: Feb 22, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Eisai Inc.: Chronic Hepatitis C related
• Additional relevant MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Thrombocytopenia; Interferons; Ribavirin

Study Results

Participant Flow

Pre-assignment Detail	The Screening Period encompassed 14 days ±7 days. Prerandomization assessments took place in all participants who had provided informed consent.

Arm/Group Title	Placebo (Core Study)	Avatrombopag 10 mg (Core Study)	Avatrombopag 20 mg (Core Study)	Avatrombopag 30 mg (Core Study)	Avatrombopag (Open Label Extension)
Arm/Group Description	Placebo, was given orally for up to 21 days once daily.	Avatrombopag 10 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 20 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 30 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag was initiated at a dose of 20 mg, once daily in the open label extension (OLE) period. The avatrombopag dose was titrated up or down in accordance with their individual response within the range of a minimum of 5 mg and a maximum of 50 mg for up to 48 weeks.
Period Title: Core Study
STARTED	17	16	18	14	0
COMPLETED	16	16	18	12	0
NOT COMPLETED	1	0	0	2	0
Period Title: Core Study
STARTED	0	0	0	0	62
COMPLETED	0	0	0	0	28
NOT COMPLETED	0	0	0	0	34

Baseline Characteristics

Arm/Group Title	Placebo (Core Study)	Avatrombopag 10 mg (Core Study)	Avatrombopag 20 mg (Core Study)	Avatrombopag 30 mg (Core Study)	Total
Arm/Group Description	Placebo, was given orally for upto 21 days once daily.	Avatrombopag 10 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 20 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 30 mg, was administered orally, once daily, preferably with food for up to 21 days.	Total of all reporting groups
Overall Participants	17	16	18	14	65
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	50.2 (7.96)	55.3 (8.06)	54.9 (7.38)	53.6 (7.26)	53.5 (7.78)
Sex: Female, Male (Count of Participants)
Female	3 17.6%	4 25%	5 27.8%	5 35.7%	17 26.2%
Male	14 82.4%	12 75%	13 72.2%	9 64.3%	48 73.8%

Outcome Measures

1. Secondary Outcome

Title	Change From Baseline of Local Platelet Count by Visit During Treatment Period A1 of Core Study
Description	Missing platelet counts were imputed using last observation carried forward (LOCF) approach for subjects who achieved platelet response at prior visits.
Time Frame	Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS), the group of all randomized participants of core study.

Arm/Group Title	Placebo (Core Study)	Avatrombopag 10 mg (Core Study)	Avatrombopag 20 mg (Core Study)	Avatrombopag 30 mg (Core Study)
Arm/Group Description	Placebo, was given orally for up to 21 days once daily.	Avatrombopag 10 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 20 mg, was administered orally, once daily, preferably with food for up to 21 days	Avatrombopag 30 mg, was administered orally, once daily, preferably with food for up to 21 days
Measure Participants	17	16	18	14
Day 7	-0.1 (7.15)	19.8 (17.59)	26.5 (22.06)	30.9 (37.65)
Day 14	-0.2 (13.79)	29.2 (18.32)	57.2 (31.39)	55.4 (37.47)

2. Secondary Outcome

Title	Number of Participants Who Achieved Platelet Count Greater Than 30 X 10^9/L From Baseline to Day 21 During Treatment Period A1 of Core Study
Description	Blood draws were taken to monitor platelet counts.
Time Frame	Baseline to Day 21

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS), the group of all randomized participants of core study.

Arm/Group Title	Placebo (Core Study)	Avatrombopag 10 mg (Core Study)	Avatrombopag 20 mg (Core Study)	Avatrombopag 30 mg (Core Study)
Arm/Group Description	Placebo, was given orally for up to 21 days once daily.	Avatrombopag 10 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 20 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 30 mg, was administered orally, once daily, preferably with food for up to 21 days.
Measure Participants	17	16	18	14
Yes	1 5.9%	9 56.3%	16 88.9%	11 78.6%
No	16 94.1%	7 43.8%	2 11.1%	3 21.4%

3. Primary Outcome

Title	Number of Participants Who Achieved Platelet Response (Greater Than or Equal to 100 x 10^9/L) by Day 21 of Treatment Period A1 of Core Study
Description	A responder was defined as a participant having a platelet count of greater than or equal to 100x10^9/L by Day 21 starting from an average baseline platelet count of greater than 20 x 10^9/L to less than or equal to 70 x 10^9/L.
Time Frame	Baseline to Day 21

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS), the group of all randomized participants of core study.

Arm/Group Title	Placebo (Core Study)	Avatrombopag 10 mg (Core Study)	Avatrombopag 20 mg (Core Study)	Avatrombopag 30 mg (Core Study)
Arm/Group Description	Placebo, was given orally for up to 21 days once daily.	Avatrombopag 10 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 20 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 30 mg, was administered orally, once daily, preferably with food for up to 21 days.
Measure Participants	17	16	18	14
Yes	1 5.9%	6 37.5%	12 66.7%	9 64.3%
No	16 94.1%	10 62.5%	6 33.3%	5 35.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (Core Study), Avatrombopag 10 mg (Core Study)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0236
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in % of Responders
	Estimated Value	31.62
	Confidence Interval	(2-Sided) 95%; 5.39 to 57.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (Core Study), Avatrombopag 20 mg (Core Study)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in % of Responders
	Estimated Value	60.78
	Confidence Interval	(2-Sided) 95%; 36.30 to 85.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo (Core Study), Avatrombopag 30 mg (Core Study)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in % of Responders
	Estimated Value	58.4
	Confidence Interval	(2-Sided) 95%; 30.92 to 85.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants Who Initiated Antiviral Treatment by Day 21 of Period A1 of Core Study
Description	Blood draws were taken to monitor platelet counts during the first 21 days of study treatment. When a platelet count of greater than or equal to 100 X 10^9/L was attained, antiviral treatment was initiated.
Time Frame	Baseline to Day 21

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS), the group of all randomized participants of core study.

Arm/Group Title	Placebo (Core Study)	Avatrombopag 10 mg (Core Study)	Avatrombopag 20 mg (Core Study)	Avatrombopag 30 mg (Core Study)
Arm/Group Description	Placebo, was given orally for up to 21 days once daily.	Avatrombopag 10 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 20 mg, was administered orally, once daily, preferably with food for up to 21 days.	Avatrombopag 30 mg, was administered orally, once daily, preferably with food for up to 21 days.
Measure Participants	17	16	18	14
Yes	1 5.9%	6 37.5%	13 72.2%	9 64.3%
No	16 94.1%	10 62.5%	5 27.8%	5 35.7%

Adverse Events

Time Frame	For each participant, treatment emergent adverse events were collected from the first day of administration of study drug up to 30 days after the last dose of study drug or up to approximately 2.5 years.
Adverse Event Reporting Description	Core Study Safety Analysis Set (SAS): All participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment. OLE Safety Analysis Set: All participants who received at least 1 dose of avatrombopag study drug (either in the Core Study or the Extension Phase) and had a postdose safety assessment.
Arm/Group Title	Placebo (Core Study)		Avatrombopag 10 mg (Core Study)		Avatrombopag 20 mg (Core Study)		Avatrombopag 30 mg (Core Study)		Avatrombopag (Open Label Extension)
Arm/Group Description	Placebo, was given orally for up to 21 days once daily.		Avatrombopag 10 mg, was administered orally, once daily, preferably with food for up to 21 days.		Avatrombopag 20 mg, was administered orally, once daily, preferably with food for up to 21 days.		Avatrombopag 30 mg, was administered orally, once daily, preferably with food for up to 21 days.		Avatrombopag was initiated at a dose of 20 mg, once daily in the open label extension (OLE) period. The avatrombopag dose was titrated up or down in accordance with their individual response within the range of a minimum of 5 mg and a maximum of 50 mg for up to 48 weeks.
All Cause Mortality
	Placebo (Core Study)		Avatrombopag 10 mg (Core Study)		Avatrombopag 20 mg (Core Study)		Avatrombopag 30 mg (Core Study)		Avatrombopag (Open Label Extension)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo (Core Study)		Avatrombopag 10 mg (Core Study)		Avatrombopag 20 mg (Core Study)		Avatrombopag 30 mg (Core Study)		Avatrombopag (Open Label Extension)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		1/14 (7.1%)		13/64 (20.3%)
Blood and lymphatic system disorders
Anaemia	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		2/64 (3.1%)
Leukopenia	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		1/64 (1.6%)
Neutropenia	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		2/64 (3.1%)
Pancytopenia	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		1/64 (1.6%)
Thrombocytopenia	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		2/64 (3.1%)
Gastrointestinal disorders
Abdominal pain	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		1/64 (1.6%)
Hepatobiliary disorders
Hepatic mass	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		1/64 (1.6%)
Infections and infestations
Gastroenteritis	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		1/64 (1.6%)
Urinary tract infection	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		1/64 (1.6%)
Metabolism and nutrition disorders
Hyperglycaemia	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		1/64 (1.6%)
Hyperuricaemia	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		1/64 (1.6%)
Nervous system disorders
Paraesthesia	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		1/64 (1.6%)
Renal and urinary disorders
Haematuria	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		1/64 (1.6%)
Renal failure acute	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		1/64 (1.6%)
Other (Not Including Serious) Adverse Events
	Placebo (Core Study)		Avatrombopag 10 mg (Core Study)		Avatrombopag 20 mg (Core Study)		Avatrombopag 30 mg (Core Study)		Avatrombopag (Open Label Extension)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/17 (35.3%)		11/16 (68.8%)		12/18 (66.7%)		11/14 (78.6%)		55/64 (85.9%)
Blood and lymphatic system disorders
Anaemia	0/17 (0%)		2/16 (12.5%)		2/18 (11.1%)		1/14 (7.1%)		21/64 (32.8%)
Leukopenia	0/17 (0%)		1/16 (6.3%)		3/18 (16.7%)		1/14 (7.1%)		14/64 (21.9%)
Lymphopenia	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		5/64 (7.8%)
Neutropenia	0/17 (0%)		2/16 (12.5%)		4/18 (22.2%)		2/14 (14.3%)		20/64 (31.3%)
Cardiac disorders
Palpitations	1/17 (5.9%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Tachycardia	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Congenital, familial and genetic disorders
Congenital lymphoedema	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Ear and labyrinth disorders
Vertigo	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Gastrointestinal disorders
Abdominal Pain	0/17 (0%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		6/64 (9.4%)
Abdominal Pain upper	1/17 (5.9%)		1/16 (6.3%)		1/18 (5.6%)		0/14 (0%)		5/64 (7.8%)
Ascites	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		6/64 (9.4%)
Diarrhoea	0/17 (0%)		1/16 (6.3%)		2/18 (11.1%)		2/14 (14.3%)		11/64 (17.2%)
Dyspepsia	0/17 (0%)		2/16 (12.5%)		0/18 (0%)		0/14 (0%)		4/64 (6.3%)
Haemorrhoids	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		1/14 (7.1%)		4/64 (6.3%)
Nausea	0/17 (0%)		3/16 (18.8%)		4/18 (22.2%)		2/14 (14.3%)		20/64 (31.3%)
Vomiting	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		8/64 (12.5%)
Abdominal distension	1/17 (5.9%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Anal pruritus	0/17 (0%)		0/16 (0%)		2/18 (11.1%)		0/14 (0%)		0/64 (0%)
Aphthous stomatitis	1/17 (5.9%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Constipation	1/17 (5.9%)		1/16 (6.3%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
Flatulence	1/17 (5.9%)		1/16 (6.3%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
Proctalgia	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
General disorders
Asthenia	0/17 (0%)		1/16 (6.3%)		2/18 (11.1%)		1/14 (7.1%)		8/64 (12.5%)
Chills	1/17 (5.9%)		3/16 (18.8%)		3/18 (16.7%)		1/14 (7.1%)		13/64 (20.3%)
Fatigue	0/17 (0%)		1/16 (6.3%)		3/18 (16.7%)		2/14 (14.3%)		16/64 (25%)
Influenza like illness	2/17 (11.8%)		1/16 (6.3%)		4/18 (22.2%)		3/14 (21.4%)		11/64 (17.2%)
Injection site erythema	0/17 (0%)		1/16 (6.3%)		1/18 (5.6%)		0/14 (0%)		6/64 (9.4%)
Irritability	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		1/14 (7.1%)		7/64 (10.9%)
Oedema peripheral	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		6/64 (9.4%)
Pyrexia	1/17 (5.9%)		0/16 (0%)		2/18 (11.1%)		2/14 (14.3%)		9/64 (14.1%)
Chest discomfort	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Feeling cold	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
Feeling of body temperature change	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Injection site pruritus	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
Pain	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
Hepatobiliary disorders
Liver tenderness	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Infections and infestations
Nasopharyngitis	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		1/14 (7.1%)		4/64 (6.3%)
Upper respiratory tract infection	0/17 (0%)		2/16 (12.5%)		0/18 (0%)		1/14 (7.1%)		4/64 (6.3%)
Abscess limb	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Cellulitis	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Gastroenteritis	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Injury, poisoning and procedural complications
Burns first degree	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Tooth fracture	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Investigations
Staphylococcus test positive	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
Weight decreased	1/17 (5.9%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Metabolism and nutrition disorders
Hyperuricaemia	1/17 (5.9%)		0/16 (0%)		1/18 (5.6%)		1/14 (7.1%)		4/64 (6.3%)
Hypertriglyceridaemia	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
Hypokalaemia	1/17 (5.9%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Muscle tightness	1/17 (5.9%)		0/16 (0%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Muscular weakness	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Nervous system disorders
Dizziness	1/17 (5.9%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		4/64 (6.3%)
Headache	1/17 (5.9%)		0/16 (0%)		3/18 (16.7%)		2/14 (14.3%)		12/64 (18.8%)
Disturbance in attention	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Dysgeusia	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Hypoaesthesia	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		1/14 (7.1%)		0/64 (0%)
Mental impairment	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Sciatica	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Somnolence	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
Syncope	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
Psychiatric disorders
Depression	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		5/64 (7.8%)
Insomnia	1/17 (5.9%)		1/16 (6.3%)		0/18 (0%)		3/14 (21.4%)		13/64 (20.3%)
Anxiety	1/17 (5.9%)		1/16 (6.3%)		1/18 (5.6%)		1/14 (7.1%)		0/64 (0%)
Food aversion	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Sleep disorder	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Mood altered	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Renal and urinary disorders
Haematuria	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Reproductive system and breast disorders
Spontaneous penile erection	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/17 (0%)		0/16 (0%)		2/18 (11.1%)		3/14 (21.4%)		9/64 (14.1%)
Dyspnoea	0/17 (0%)		0/16 (0%)		2/18 (11.1%)		0/14 (0%)		4/64 (6.3%)
Dyspnoea exertional	0/17 (0%)		1/16 (6.3%)		1/18 (5.6%)		1/14 (7.1%)		4/64 (6.3%)
Epistaxis	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		2/14 (14.3%)		6/64 (9.4%)
Productive cough	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		1/14 (7.1%)		0/64 (0%)
Respiratory tract congestion	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)
Upper-airway cough syndrome	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Skin and subcutaneous tissue disorders
Pruritus	0/17 (0%)		4/16 (25%)		0/18 (0%)		2/14 (14.3%)		15/64 (23.4%)
Rash	2/17 (11.8%)		1/16 (6.3%)		2/18 (11.1%)		1/14 (7.1%)		12/64 (18.8%)
Rash macular	0/17 (0%)		0/16 (0%)		0/18 (0%)		1/14 (7.1%)		0/64 (0%)
Vascular disorders
Hot flush	0/17 (0%)		1/16 (6.3%)		0/18 (0%)		0/14 (0%)		0/64 (0%)
Pallor	0/17 (0%)		0/16 (0%)		1/18 (5.6%)		0/14 (0%)		0/64 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.