A Study to Investigate the Efficacy and Safety of Lusutrombopag (S-888711) Tablets Administered to Adults With Immune Thrombocytopenia (ITP)

• Sponsor: Shionogi (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01054443
• Collaborator: (none)
• Enrollment: 20
• Locations: 19
• Arms: 4
• Actual Duration (Months): 8.2
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study was to assess the efficacy of 3 dose levels of lusutrombopag (0.5 mg, 0.75 mg, and 1.0 mg) and placebo on platelet count.

Condition or Disease	Intervention/Treatment	Phase
Immune Thrombocytopenia (ITP)	Drug: Placebo; Drug: Lusutrombopag	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Investigate the Efficacy and Safety of S-888711 Tablets Administered Once-daily for 42 Days to Adult Subjects With Relapsed Persistent or Chronic Immune Thrombocytopenia With or Without Prior Splenectomy
• Actual Study Start Date: Mar 18, 2010
• Actual Primary Completion Date: Nov 24, 2010
• Actual Study Completion Date: Nov 24, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo tablets orally once a day for 42 days.	Drug: Placebo; Tablet
Experimental: Lusutrombopag 0.5 mg Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Drug: Lusutrombopag; Tablet; Other Names: MULPLETA® S-888711
Experimental: Lusutrombopag 0.75 mg Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Drug: Lusutrombopag; Tablet; Other Names: MULPLETA® S-888711
Experimental: Lusutrombopag 1.0 mg Participants received 1.0 mg lusutrombopag orally once a day for 42 days.	Drug: Lusutrombopag; Tablet; Other Names: MULPLETA® S-888711

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Response [Week 6]

   Responders were participants with one of the following: achieved a platelet count of ≥ 50,000 cells/µL after 6 weeks of dosing; or prematurely withdrawn due to a platelet count > 400,000 cells/µL prior to Day 42. Participants were counted as non-responders if any of the following conditions held: The above conditions were not satisfied; They received rescue medications; They satisfied the above conditions after receiving restricted medications during the treatment period; They had achieved a platelet count of ≥ 50,000 cells/µL before Week 6 but not after Week 6; or They withdrew for any reason other than a platelet count > 400,000 cells/µL.

Secondary Outcome Measures

1. Change From Baseline in Platelet Count at Week 6 [Baseline and Week 6]

2. Duration of Response [6 weeks]

   Duration of response was defined as the percentage of the cumulative time a platelet count was ≥ 50,000 cells/µL during the treatment period.

3. Percentage of Participants Who Achieved a Platelet Count of ≥ 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing [Week 6]

4. Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing [Week 6]

5. Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period, [6 weeks]

   Bleeding assessments were performed by the Investigator according to the World Health Organization (WHO) criteria bleeding scale: Grade 0: no bleeding; Grade 1: petechial bleeding; Grade 2: mild blood loss (clinically significant); Grade 3: gross blood loss, requires transfusion (severe); Grade 4: debilitating blood loss, retinal or cerebral associated with fatality. For each participant, the most severe WHO bleeding grade observed during the 6-week treatment period is reported.

6. Number of Participants Who Received Rescue Medication During the Treatment Period [6 weeks]

7. Number of Participants With Adverse Events (AEs) [6 weeks]

   An AE is defined as any untoward medical occurrence in a subject administered a pharmaceutical product during the course of a clinical investigation, including any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product (IP), whether or not thought to be related to the IP. AEs reported after initial study drug administration were considered treatment-emergent. A serious adverse event is defined as any AE that resulted in death, was life-threatening, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect or an important medical event that, based upon medical judgment, may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. A treatment-related AE is any AE determined by the investigator to be possibly related, probably related, or definitely related to study drug.

8. Lusutrombopag Plasma Concentration [Days 8, 22, and 36, after dosing]

   Plasma concentrations of lusutrombopag were determined using a validated liquid chromatography mass spectrometry method. The lower limit of quantification (LOQ) for the plasma assay for lusutrombopag was 0.1 ng/mL.

9. Plasma Concentration of Metabolite S-888711 Deshexyl [Days 8, 22, and 36, after dosing]

   Plasma concentrations of the major metabolite S-888711 deshexyl were determined using a validated liquid chromatography mass spectrometry method. The lower limit of quantification (LOQ) for the plasma assay for S-888711 deshexyl was 0.1 ng/mL.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• A signed and dated written informed consent

• Males and females ≥ 18 years of age

• All subjects must agree to use barrier contraception

• Diagnosis of ITP

• Subjects > 60 years must have had a diagnostic bone marrow aspiration

• Relapsed persistent or chronic ITP status, with or without prior splenectomy (exception: in Hungary only splenectomized subjects will be enrolled), after having failed at least 1 prior ITP therapy (excluding TPO agonists) and have a platelet count < 30,000/μL if not taking medications or < 50,000/μL despite concomitant steroids or other ITP therapies, such as danazol or immunosuppressive drugs

• Subjects receiving steroid therapy must be on a stable dose

• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) within 20% of the upper limit of normal (ULN)

• Subjects receiving stable dosages of cyclosporine A, mycophenolate mofetil, azathioprine, or danazol are allowed. The dosages of all these medications must be stable for at least 4 weeks prior to Visit 1 (Day 1)

Exclusion Criteria:

• History of clinically important hemorrhagic clotting disorder

• Females who are pregnant, lactating, or taking oral contraceptives

• History of alcohol/drug abuse or dependence within 1 year

• Use of the following drugs or treatment prior to Visit 1 (Day 1):

• Within 12 weeks - alemtuzumab, multi-drug systemic chemotherapy, stem cell therapy;

• Within 8 weeks - rituximab

• Within 2 weeks - platelet transfusions or plasmapheresis treatment

• Within 4 weeks - use of anti-platelet or anti-coagulant drugs

• Within 1 week - Rho(D) immune globulin or intravenous immunoglobulin

• History of clinically significant cardiovascular or thromboembolic disease within 26 weeks prior to Screening

• Splenectomy within 4 weeks prior to Screening

• Clinically significant laboratory abnormalities

• Hemoglobin < 10.0 g/dL for men or women, not clearly related to ITP

• Absolute neutrophil count < 1000/mm^3

• Abnormal peripheral blood smear

• Total bilirubin > 1.5 x upper limit of normal

• Alanine aminotransferase (ALT) > 1.5 x upper limit of normal

• Aspartate aminotransferase (AST) > 1.5 x upper limit of normal

• Creatinine > 1.5 x upper limit of normal

• Human immunodeficiency virus (HIV) positive

• Hepatitis A immunoglobulin M antibody (IgM HAV) positive, hepatitis B surface antigen (HbsAg) or hepatitis C antibody (HCV) positive

• Thyroid stimulating hormone (TSH) > 1.5 x upper limit of normal

• Free thyroxine (T4) > 1.5 x upper limit of normal

• Exposure to previous thrombopoietin (TPO) mimetics/agonists (e.g., eltrombopag,romiplostim, E5501 [AKR-501] or LGD-4665) within 4 weeks prior to Screening

• Subjects unresponsive to previous TPO mimetics/agonists (e.g., eltrombopag, romiplostim, E5501 [AKR-501] or LGD-4665)

• Exposure to an investigative medication within the past 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator	Anaheim	California	United States	92801
2	Investigator	Los Angeles	California	United States	90272
3	Investigator	Washington	District of Columbia	United States	20007
4	Investigator	Boynton Beach	Florida	United States	33426
5	Investigator	Jacksonville	Florida	United States	32207
6	Investigator	Atlanta	Georgia	United States	30341
7	Investigator	Riverdale	Georgia	United States	30274
8	Investigator	Metairie	Louisiana	United States	70006
9	Investigator	Bethesda	Maryland	United States	20817
10	Investigator	Boston	Massachusetts	United States	02114
11	Investigator	Jefferson City	Missouri	United States	65109
12	Investigator	Kansas City	Missouri	United States	64131
13	Investigator	New Brunswick	New Jersey	United States	08903
14	Investigator	New York	New York	United States	10021
15	Investigator	New York	New York	United States	10029
16	Investigator	Cleveland	Ohio	United States	44106
17	Investigator	San Antonio	Texas	United States	78229
18	Investigator	Salt Lake City	Utah	United States	84132
19	Investigator	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Shionogi

Investigators

• Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line, Shionogi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shionogi
• ClinicalTrials.gov Identifier: NCT01054443
• Other Study ID Numbers: 0913M0621
• First Posted: Jan 22, 2010
• Last Update Posted: Mar 18, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Shionogi: Blood Platelet Disorders; Immune Thrombocytopenia (ITP); Low Platelet Count; Thrombocytopaenia; S-888711; Splenectomy; Thrombopoiesis; Hematologic Disease; Auto-immune thrombocytopenic Purpura; Relapsed Persistent or Chronic ITP; Idiopathic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura (TTP)
• Additional relevant MeSH terms: Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized in a 1:1:1:1 ratio to 1 of 4 treatment groups to receive lusutrombopag 0.5 mg, 0.75 mg, or 1.0 mg or placebo administered orally once daily for 42 days. Randomization was stratified according to Screening platelet count (< 30,000 cells/μL or ≥ 30,000 cells/μL to < 50,000 cells/μL).

Arm/Group Title	Placebo	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Period Title: Overall Study
STARTED	5	5	5	5
COMPLETED	5	5	5	4
NOT COMPLETED	0	0	0	1

Baseline Characteristics

Arm/Group Title	Placebo	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg	Total
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.	Total of all reporting groups
Overall Participants	5	5	5	5	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (18.24)	59.2 (24.60)	55.0 (23.40)	43.2 (15.39)	54.7 (20.36)
Sex: Female, Male (Count of Participants)
Female	3 60%	4 80%	1 20%	4 80%	12 60%
Male	2 40%	1 20%	4 80%	1 20%	8 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 20%	0 0%	1 20%	0 0%	2 10%
Not Hispanic or Latino	4 80%	5 100%	4 80%	5 100%	18 90%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	4 80%	5 100%	5 100%	5 100%	19 95%
Black or African American	1 20%	0 0%	0 0%	0 0%	1 5%
Platelet Count at Screening (Count of Participants)
< 30,000 cells /μL	5 100%	5 100%	4 80%	5 100%	19 95%
≥ 30,000 cells/μL to < 50,000 cells/μL	0 0%	0 0%	1 20%	0 0%	1 5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Response
Description	Responders were participants with one of the following: achieved a platelet count of ≥ 50,000 cells/µL after 6 weeks of dosing; or prematurely withdrawn due to a platelet count > 400,000 cells/µL prior to Day 42. Participants were counted as non-responders if any of the following conditions held: The above conditions were not satisfied; They received rescue medications; They satisfied the above conditions after receiving restricted medications during the treatment period; They had achieved a platelet count of ≥ 50,000 cells/µL before Week 6 but not after Week 6; or They withdrew for any reason other than a platelet count > 400,000 cells/µL.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized participants who received at least 1 dose of study drug and had a platelet count at Baseline and at least 1 platelet count after randomized study drug was taken.

Arm/Group Title	Placebo	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Measure Participants	5	5	5	5
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	20.0 400%	0.0 0%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lusutrombopag 0.5 mg, Lusutrombopag 0.75 mg, Lusutrombopag 1.0 mg
	Comments	The primary efficacy evaluation was to test if there was a linear relationship existing such that the higher the dose level, the larger the percentage of responders. The Cochran-Armitage trend test was employed by assigning the score 0, 0.5, 0.75, and 1 to placebo, lusutrombopag 0.5, 0.75, and 1.0 mg group, respectively, at the 0.025 level of significance (1-sided) to determine the test statistic for detecting a dose-response in the percentage of responders.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.431
	Comments
	Method	Cochran-Armitage Trend Test
	Comments
Method of Estimation	Estimation Parameter	Cochran-Armitage Trend Test Statistic
	Estimated Value	0.173
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Platelet Count at Week 6
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

Full analysis set participants who completed 6 weeks of treatment.

Arm/Group Title	Placebo	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Measure Participants	5	5	5	4
Least Squares Mean (Standard Error) [cells/µL]	-3566.0 (6400.05)	21978.1 (6095.54)	8235.4 (6465.37)	-2809.4 (6866.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lusutrombopag 0.5 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	25544.0
	Confidence Interval	(2-Sided) 95%; 6202.8 to 44885.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference of least squares means (LSMeans) between each of the lusutrombopag treatment groups and placebo was estimated after adjusting for the Baseline platelet count using analysis of covariance (ANCOVA).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lusutrombopag 0.75 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11801.3
	Confidence Interval	(2-Sided) 95%; -8809.3 to 32411.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference of least squares means (LSMeans) between each of the lusutrombopag treatment groups and placebo was estimated after adjusting for the Baseline platelet count using analysis of covariance (ANCOVA).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lusutrombopag 1.0 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	756.6
	Confidence Interval	(2-Sided) 95%; -18794.3 to 20307.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference of least squares means (LSMeans) between each of the lusutrombopag treatment groups and placebo was estimated after adjusting for the Baseline platelet count using analysis of covariance (ANCOVA).

3. Secondary Outcome

Title	Duration of Response
Description	Duration of response was defined as the percentage of the cumulative time a platelet count was ≥ 50,000 cells/µL during the treatment period.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Participants in the full analysis set with platelet counts ≥ 50,000 cells/μL at any time during the 6-week treatment period.

Arm/Group Title	Placebo	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Measure Participants	0	4	3	1
Median (Full Range) [percentage of days]	0.399	0.426	0.103

4. Secondary Outcome

Title	Percentage of Participants Who Achieved a Platelet Count of ≥ 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Participants in the full analysis set who completed 6 weeks of treatment

Arm/Group Title	Placebo	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Measure Participants	5	5	5	4
Number [percentage of participants]	0.0 0%	60.0 1200%	20.0 400%	0.0 0%

5. Secondary Outcome

Title	Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Participants in the full analysis set who completed 6 weeks of treatment

Arm/Group Title	Placebo	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Measure Participants	5	5	5	4
Number [percentage of participants]	0.0 0%	40.0 800%	0.0 0%	0.0 0%

6. Secondary Outcome

Title	Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period,
Description	Bleeding assessments were performed by the Investigator according to the World Health Organization (WHO) criteria bleeding scale: Grade 0: no bleeding; Grade 1: petechial bleeding; Grade 2: mild blood loss (clinically significant); Grade 3: gross blood loss, requires transfusion (severe); Grade 4: debilitating blood loss, retinal or cerebral associated with fatality. For each participant, the most severe WHO bleeding grade observed during the 6-week treatment period is reported.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Measure Participants	5	5	5	5
Grade 0	0 0%	0 0%	2 40%	0 0%
Grade 1	2 40%	3 60%	2 40%	3 60%
Grade 2	3 60%	2 40%	1 20%	2 40%
Grade 3	0 0%	0 0%	0 0%	0 0%
Grade 4	0 0%	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants Who Received Rescue Medication During the Treatment Period
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Measure Participants	5	5	5	5
Count of Participants [Participants]	1 20%	2 40%	3 60%	2 40%

8. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An AE is defined as any untoward medical occurrence in a subject administered a pharmaceutical product during the course of a clinical investigation, including any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product (IP), whether or not thought to be related to the IP. AEs reported after initial study drug administration were considered treatment-emergent. A serious adverse event is defined as any AE that resulted in death, was life-threatening, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect or an important medical event that, based upon medical judgment, may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. A treatment-related AE is any AE determined by the investigator to be possibly related, probably related, or definitely related to study drug.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least 1 dose of study drug

Arm/Group Title	Placebo	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Measure Participants	5	5	5	5
Any treatment-emergent adverse event	4 80%	5 100%	5 100%	4 80%
Serious adverse events	0 0%	0 0%	0 0%	1 20%
Treatment-related adverse events	1 20%	1 20%	0 0%	2 40%
Treatment-related serious adverse events	0 0%	0 0%	0 0%	0 0%
Adverse events leading to withdrawal of study drug	0 0%	0 0%	0 0%	0 0%

9. Secondary Outcome

Title	Lusutrombopag Plasma Concentration
Description	Plasma concentrations of lusutrombopag were determined using a validated liquid chromatography mass spectrometry method. The lower limit of quantification (LOQ) for the plasma assay for lusutrombopag was 0.1 ng/mL.
Time Frame	Days 8, 22, and 36, after dosing

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug

Arm/Group Title	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Measure Participants	5	5	5
Day 8	16.5 (35.40)	21.7 (52.77)	33.3 (32.74)
Day 22	19.1 (32.10)	19.6 (32.20)	30.7 (42.97)
Day 36	24.1 (14.22)	21.1 (36.33)	30.4 (40.28)

10. Secondary Outcome

Title	Plasma Concentration of Metabolite S-888711 Deshexyl
Description	Plasma concentrations of the major metabolite S-888711 deshexyl were determined using a validated liquid chromatography mass spectrometry method. The lower limit of quantification (LOQ) for the plasma assay for S-888711 deshexyl was 0.1 ng/mL.
Time Frame	Days 8, 22, and 36, after dosing

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug, with available data at each time point.

Arm/Group Title	Lusutrombopag 0.5 mg	Lusutrombopag 0.75 mg	Lusutrombopag 1.0 mg
Arm/Group Description	Participants received 0.5 mg lusutrombopag orally once a day for 42 days.	Participants received 0.75 mg lusutrombopag orally once a day for 42 days.	Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
Measure Participants	5	5	5
Day 8	0.1 (68.10)	0.3 (176.69)	0.2 (50.41)
Day 22	0.1 (23.87)	0.2 (141.38)	0.2 (50.20)
Day 36	0.1 (28.15)	0.2 (154.49)	0.2 (101.93)

Adverse Events

Time Frame	6 weeks
Arm/Group Title	Placebo		Lusutrombopag 0.5 mg		Lusutrombopag 0.75 mg		Lusutrombopag 1.0 mg
Arm/Group Description	Participants received placebo tablets orally once a day for 42 days.		Participants received 0.5 mg lusutrombopag orally once a day for 42 days.		Participants received 0.75 mg lusutrombopag orally once a day for 42 days.		Participants received 1.0 mg lusutrombopag orally once a day for 42 days.
All Cause Mortality
	Placebo		Lusutrombopag 0.5 mg		Lusutrombopag 0.75 mg		Lusutrombopag 1.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Placebo		Lusutrombopag 0.5 mg		Lusutrombopag 0.75 mg		Lusutrombopag 1.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Renal and urinary disorders
Renal vein thrombosis	0/5 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Other (Not Including Serious) Adverse Events
	Placebo		Lusutrombopag 0.5 mg		Lusutrombopag 0.75 mg		Lusutrombopag 1.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		5/5 (100%)		5/5 (100%)		4/5 (80%)
Blood and lymphatic system disorders
Leukocytosis	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Eye disorders
Conjunctival haemorrhage	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Conjunctival hyperaemia	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Vision blurred	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/5 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Dry mouth	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Faeces discoloured	0/5 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Flatulence	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Gingival bleeding	0/5 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Infrequent bowel movements	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Mouth haemorrhage	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Nausea	0/5 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
Rectal haemorrhage	0/5 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
General disorders
Oedema peripheral	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Cyst	0/5 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Fatigue	0/5 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Inflammation	0/5 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Oedema	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Vessel puncture site haemorrhage	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Muscle spasms	0/5 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Infections and infestations
Upper respiratory tract infection	0/5 (0%)		1/5 (20%)		1/5 (20%)		1/5 (20%)
Nasopharyngitis	0/5 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Injury, poisoning and procedural complications
Contusion	0/5 (0%)		3/5 (60%)		0/5 (0%)		0/5 (0%)
Fall	0/5 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
Injury	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Skin laceration	0/5 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Investigations
Platelet count decreased	0/5 (0%)		0/5 (0%)		1/5 (20%)		1/5 (20%)
Blood glucose increased	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Metabolism and nutrition disorders
Gout	0/5 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/5 (20%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
Musculoskeletal chest pain	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Musculoskeletal stiffness	0/5 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Myalgia	0/5 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
Pain in extremity	0/5 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Nervous system disorders
Headache	1/5 (20%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Clumsiness	0/5 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
Dizziness	0/5 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
Psychiatric disorders
Insomnia	1/5 (20%)		1/5 (20%)		0/5 (0%)		1/5 (20%)
Anxiety	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Renal and urinary disorders
Dysuria	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Reproductive system and breast disorders
Amenorrhoea	0/5 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)
Menorrhagia	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/5 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Epistaxis	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Skin and subcutaneous tissue disorders
Rash pruritic	0/5 (0%)		0/5 (0%)		1/5 (20%)		0/5 (0%)
Dry skin	0/5 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
Petechiae	1/5 (20%)		0/5 (0%)		0/5 (0%)		0/5 (0%)
Social circumstances
Victim of sexual abuse	0/5 (0%)		1/5 (20%)		0/5 (0%)		0/5 (0%)
Vascular disorders
Hot flush	0/5 (0%)		0/5 (0%)		1/5 (20%)		1/5 (20%)
Raynaud's phenomenon	0/5 (0%)		0/5 (0%)		0/5 (0%)		1/5 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.