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Eltrombopag Phase III Study In Chinese Chronic ITP Patients

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ClinicalTrials.gov Identifier: NCT01762761
Recruitment Status : Completed
First Posted : January 8, 2013
Results First Posted : March 9, 2015
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Purpura, Thrombocytopenic, Idiopathic and Hepatitis C
Interventions Drug: eltrombopag
Drug: placebo
Enrollment 155
Recruitment Details This study includes three stages: 8-week double-blind stage (Stage 1), 24-week open-label stage (Stage 2) and prolonged open-label stage (Stage 3) with voluntary participation until eltrombopag becomes commercially available in China. Results for Stage 1 are presented in this report.
Pre-assignment Details Participants diagnosed with primary immune thrombocytopenia (ITP) for at least 12 months prior to randomization, platelet count of <30×10^9/Liter (L) within 48 hours (hrs) prior to Day 1; no response or relapsed after splenectomy or if not splenectomised and either not responded to prior therapies or relapsed to prior therapy were enrolled.
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks. Participants initially received eltrombopag 25 milligrams (mg) QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Period Title: Overall Study
Started 51 104
Completed 49 100
Not Completed 2 4
Reason Not Completed
Adverse Event             1             2
Lack of Efficacy             1             0
Protocol Violation             0             1
Physician Decision             0             1
Arm/Group Title Placebo Eltrombopag Total
Hide Arm/Group Description Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks. Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 51 104 155
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants 104 participants 155 participants
41.3  (12.83) 44.7  (15.91) 43.6  (15.01)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 104 participants 155 participants
Female
40
  78.4%
77
  74.0%
117
  75.5%
Male
11
  21.6%
27
  26.0%
38
  24.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Asian - East Asian Heritage Number Analyzed 51 participants 104 participants 155 participants
51 104 155
1.Primary Outcome
Title Number of Participants (Responders) Achieving a Platelet Count >=50×10^9/L After the First 6 Weeks of Stage 1
Hide Description The number of participants (responders) with platelet count >=50x10^9/L after 6 weeks of Stage 1 were compared between treatments using a logistic regression model adjusted for use of primary immune thrombocytopenia (ITP) medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count <=15×10^9/L (yes/no) and treatment. Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6. Primary Analysis Data Set: a participant who withdrawals from Stage 1 or is emergently unblinded was classified as a negative response from the time of withdrawal or unblinding date and for all subsequent visits. In the event of a participant dying, information for all subsequent assessments would be considered missing. All intermittent missing data (apart from withdrawals) will be treated as missing.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants who received at least one dose of study medication and with at least one platelet count post-Baseline in Stage 1.
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Measure Type: Number
Unit of Measure: Participants
3 60
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Eltrombopag
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 26.08
Confidence Interval (2-Sided) 95%
7.29 to 93.26
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants Achieving a Platelet Count >=50×10^9/L at Least Once During the First 6 Weeks of Stage 1
Hide Description The number of participants (responders) with platelet count >=50×10^9/L at least once during the first 6 weeks of Stage 1 were compared between treatments using a logistic regression model adjusted for use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count <=15×10^9/L (yes/no) and treatment. Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Measure Type: Number
Unit of Measure: Participants
9 80
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Eltrombopag
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 23.80
Confidence Interval (2-Sided) 95%
8.54 to 66.33
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants Achieving a Platelet Count >=30×10^9/L and at Least 2 Times the Baseline Platelet Count at Least Once During the 6 Weeks of Stage 1
Hide Description The number of participants achieving a platelet count >=30×10^9/L and at least 2 times the Baseline platelet count at least once during the first 6 weeks of Stage 1 were analyzed. The Baseline platelet count is defined as the platelet count taken on Day 1 of the study or within 48 hours prior to the first dose of investigational product. Logistic regression analysis was adjusted for use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count <=15×10^9/L (yes/no) and treatment. Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. One participant did not have a Baseline platelet count due to no platelet count collected on Day 1 or within 48 hours prior to the first dose of investigational product;therefore, this participant was not evaluable in this table.
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 103
Measure Type: Number
Unit of Measure: Participants
18 84
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Eltrombopag
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 8.52
Confidence Interval (2-Sided) 95%
3.84 to 18.94
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale
Hide Description The WHO Bleeding Scale is a measure of bleeding severity with the following grades: grade 0 = no bleeding, grade 1= petechiae, grade 2= mild blood loss, grade 3 = gross blood loss, and grade 4 = debilitating blood loss. The WHO Bleeding Scale were dichotomized to indicate no bleeding vs bleeding, i.e. 0=grade 0 and 1=grades 1, 2, 3 or 4. Generalized linear mixed model was applied with a Logit canonical link function for repeated binary data, allowing for Baseline dichotomized WHO bleeding grade, use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count <=15×10^9/L (yes/no) and treatment as fixed effects, and the participant was treated as a random effect. Bleeding incidences were recorded at Screening, Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6. All Bleeding incidences at each visit are presented.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Measure Type: Number
Unit of Measure: Participants
Baseline Number Analyzed 50 participants 104 participants
36 68
Week 1 Number Analyzed 50 participants 102 participants
30 43
Week 2 Number Analyzed 49 participants 103 participants
27 32
Week 3 Number Analyzed 49 participants 100 participants
26 29
Week 4 Number Analyzed 50 participants 102 participants
24 23
Week 5 Number Analyzed 47 participants 100 participants
19 24
Week 6 Number Analyzed 46 participants 98 participants
17 17
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Eltrombopag
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.13 to 0.59
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With Clinically Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale
Hide Description The WHO Bleeding Scale is a measure of bleeding severity with the following grades: grade 0 = no bleeding, grade 1= petechiae, grade 2= mild blood loss, grade 3 = gross blood loss, and grade 4 = debilitating blood loss. The WHO Bleeding Scale grades were dichotomized into the following categories: no clinically significant bleeding = Grade 0 to 1; clinically significant bleeding = Grade 2 to 4. Generalized linear mixed model with a Logit canonical link function for repeated binary data, allowing for Baseline dichotomized WHO bleeding grade, use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count <=15×10^9/L (yes/no) and treatment as fixed effects, and the participant was treated as a random effect.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Measure Type: Number
Unit of Measure: Participants
Baseline, n= 50, 104 Number Analyzed 50 participants 104 participants
5 14
Week 1 Number Analyzed 50 participants 102 participants
5 12
Week 2 Number Analyzed 49 participants 103 participants
4 13
Week 3 Number Analyzed 49 participants 100 participants
6 11
Week 4 Number Analyzed 50 participants 102 participants
5 7
Week 5 Number Analyzed 47 participants 100 participants
2 8
Week 6 Number Analyzed 46 participants 98 participants
4 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Eltrombopag
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.306
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.21 to 1.64
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Response
Hide Description Time to response is defined as time from the startin of treatment to the first time of achieving a platelet count >=50x10^9/L during the first 6 weeks of Stage 1. Time to response is summarized using Kaplan-Meier estimates and compared between treatment groups using a stratified log-rank test, stratifying for the use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count <=15x10^9/L (yes/no). The pike estimator of the treatment hazard ratio is based on the stratified log-rank test. Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.Only those participants (par.) with a response were analyzed (3 responders out of 50 participants in the placebo group and 60 responders out of 104 participants in the Eltrombopag group for calculating the statistics of time to response analysis).
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Median (95% Confidence Interval)
Unit of Measure: Weeks
NA [1] 
(NA to NA)
3.14
(3.00 to 4.14)
[1]
The analysis was limited to only par. with a response (3 responders out of the 50 par. in the placebo group). Due to low event incidence observed in placebo group, the median time and the CI could not be calculated from the Kaplan-Meier estimates.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Eltrombopag
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 6.12
Confidence Interval (2-Sided) 95%
4.01 to 9.34
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants Who Required Protocol-defined Rescue Treatment During the First 6 Weeks of Stage 1
Hide Description Rescue treatment is defined as either a new ITP medication, an increase in dose of concomitant ITP medication from Baseline, a platelet transfusion, or a splenectomy. Logistic regression analysis was adjusted for use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count <=15x10^9/L (yes/no) and treatment.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Measure Type: Number
Unit of Measure: Participants
17 9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Eltrombopag
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
0.05 to 0.37
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With a Platelet Count >=50×10^9/L During at Least 75% of Their Platelet Count Assessments
Hide Description The number of participants with a platelet count >=50×10^9/L during at least 75% of their platelet count assessments was analyzed up to the end of Week 6 of Stage 1. Logistic regression analysis was adjusted for use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count <=15x10^9/L (yes/no) and treatment. Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Measure Type: Number
Unit of Measure: Participants
1 23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Eltrombopag
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 16.54
Confidence Interval (2-Sided) 95%
2.09 to 131.12
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Total Duration of Time a Participant Had a Platelet Count >=50×10^9/L
Hide Description Total duration of time a participant had platelet count >=50 x 10^9/L was analyzed using the van Elteren stratified rank test with stratification factors including the use of ITP medication at Baseline (yes/no), splenectomy (yes/no) and Baseline platelet count <=15x10^9/L (yes/no). Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Median (Inter-Quartile Range)
Unit of Measure: Weeks
0.00
(0.00 to 0.00)
1.79
(0.14 to 3.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Eltrombopag
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method van Elteren stratified rank test
Comments [Not Specified]
10.Secondary Outcome
Title Maximum Period of Time a Participant Had a Platelet Count Continuously >= 50 ×10^9/L
Hide Description Maximum period of time a participant had a platelet count continously >=50 x 10^9/L was analyzed using the van Elteren stratified rank test with stratification factors including the use of ITP medication at Baseline (yes/no), splenectomy (yes/no) and Baseline platelet count <=15x10^9/L (yes/no). Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Median (Inter-Quartile Range)
Unit of Measure: Weeks
0.00
(0.00 to 0.00)
1.57
(0.14 to 3.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Eltrombopag
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method van Elteren stratified rank test
Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants That Reduced or Discontinued Baseline Concomitant ITP Medications During Stage 2 and Stage 3
Hide Description The number of participants taking concomitant ITP medications on Day 1 of Stage 1 who had a decrease in the dose or frequency of ITP medication or stopped ITP medication at any point during Stage 2 or Stage 3 will be presented. The Baseline concomitant ITP medication for Stage 2 and Stage 3 is defined as ITP medications taken prior to the first dose of investigational product of Stage 1. This study is still ongoing and this endpoint can only be analyzed when the stage 2 and stage 3 complete.
Time Frame From the start of Week 1 of Stage 2 to the end of last week of Stage 3
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Hide Description An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product.A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, is a congenital anomaly/birth defect or is associated with protocol specified liver injury and impaired liver function or is any protocol specific AEs.
Time Frame From the start of study treatment (Day 1) up to the end of Week 8 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all randomized participants who received at least one dose of the study treatment.
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 51 104
Measure Type: Number
Unit of Measure: Participants
Any AE 34 66
Any SAE 5 5
13.Secondary Outcome
Title Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters
Hide Description Clinical chemistry parameters aspartate amino transferase (AST), alanine amino transferase (ALT), gamma glutamyl transferase (GGT), total bilirubin, albumin, alkaline phosphatase, calcium, potassium, creatinine, glucose and sodium were evaluated at Baseline, at all on therapy visits, and at Week 1, Week 2, Week 3, and Week 4 visits during the follow-up period and were summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 (NCI CTCAE V4.0): Grade 0, none; Grade 1, mild; Grade 2, moderate; Grade 3, severe or medically significant; Grade 4, life-threatening consequences; Grade 5, death related to AE. Day 1 assessment was considered as Baseline; if Day 1 was not available then Screening assessment is taken as Baseline. For creatinine, Baseline is defined as the average of Screening and Day 1 values if available and prior to first dose. Maximum post-Baseline toxicity grade included any scheduled or unscheduled post-Baseline assessment
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Measure Type: Number
Unit of Measure: Participants
AST, Grade 1 8 10
AST, Grade 2 0 2
AST, Grade 3 0 0
AST, Grade 4 0 0
AST, Grade 5 0 0
ALT, Grade 1 11 14
ALT, Grade 2 2 1
ALT, Grade 3 1 1
ALT, Grade 4 0 0
ALT, Grade 5 0 0
GGT,Grade 1 10 10
GGT,Grade 2 2 2
GGT,Grade 3 0 0
GGT,Grade 4 0 0
GGT,Grade 5 0 0
Total Bilirubin, Grade 1 2 17
Total Bilirubin, Grade 2 0 1
Total Bilirubin, Grade 3 0 0
Total Bilirubin, Grade 4 0 0
Total Bilirubin, Grade 5 0 0
Albumin, Grade 1 2 10
Albumin, Grade 2 1 2
Albumin, Grade 3 0 0
Albumin, Grade 4 0 0
Albumin, Grade 5 0 0
Alkaline Phosphatase, Grade 1 1 8
Alkaline Phosphatase, Grade 2 0 0
Alkaline Phosphatase, Grade 3 0 0
Alkaline Phosphatase, Grade 4 0 0
Alkaline Phosphatase, Grade 5 0 0
Calcium, Grade 1 4 16
Calcium, Grade 2 5 13
Calcium, Grade 3 0 0
Calcium, Grade 4 0 0
Calcium, Grade 5 0 0
Potassium, Grade 1 25 25
Potassium, Grade 2 0 1
Potassium, Grade 3 1 7
Potassium, Grade 4 0 0
Potassium, Grade 5 0 0
Creatinine, Grade 1 0 2
Creatinine, Grade 2 0 0
Creatinine, Grade 3 0 0
Creatinine, Grade 4 0 1
Creatinine, Grade 5 0 0
Glucose, Grade 1 14 34
Glucose, Grade 2 4 13
Glucose, Grade 3 2 2
Glucose, Grade 4 0 0
Glucose, Grade 5 0 0
Sodium, Grade 1 10 19
Sodium, Grade 2 0 0
Sodium, Grade 3 0 1
Sodium, Grade 4 0 0
Sodium, Grade 5 0 0
14.Secondary Outcome
Title Number of Participants With the Maximum Toxicity Grade for the Indicated Hematology Parameters
Hide Description Clinical hematology parameters hemoglobin, lymphocytes, platelet count, total neutrophils, white blood cell count evaluations were performed at Baseline, at all on-therapy visits, and at Week 1, Week 2, Week 3, and Week 4 visits during the follow-up period and were summarized according to the NCI CTCAE V4.0: Grade 0, none; Grade 1, mild; Grade 2, moderate; Grade 3, severe or medically significant; Grade 4, life-threatening consequences; Grade 5, death related to AE. Day 1 assessment was considered as Baseline; if Day 1 was not available then Screening assessment is taken as Baseline. Maximum post-Baseline toxicity grade included any scheduled or unscheduled post-Baseline assessment.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Measure Type: Number
Unit of Measure: Participants
Hemoglobin, Grade 1 21 35
Hemoglobin, Grade 2 1 11
Hemoglobin, Grade 3 3 4
Hemoglobin, Grade 4 0 0
Hemoglobin, Grade 5 0 0
Lymphocytes, Grade 1 0 2
Lymphocytes, Grade 2 12 16
Lymphocytes, Grade 3 0 1
Lymphocytes, Grade 4 0 0
Lymphocytes, Grade 5 0 0
Platelet count, Grade 1 1 1
Platelet count, Grade 2 0 11
Platelet count, Grade 3 5 26
Platelet count, Grade 4 44 66
Platelet count, Grade 5 0 0
Total Neutrophils, Grade 1 5 7
Total Neutrophils, Grade 2 3 3
Total Neutrophils, Grade 3 0 0
Total Neutrophils, Grade 4 0 0
Total Neutrophils, Grade 5 0 0
White Blood Cell Count, Grade 1 4 9
White Blood Cell Count, Grade 2 1 2
White Blood Cell Count, Grade 3 0 0
White Blood Cell Count, Grade 4 0 0
White Blood Cell Count, Grade 5 0 0
15.Secondary Outcome
Title Change From Baseline in Systolic Blood Pressure
Hide Description Systolic blood pressure was measured in the sitting position at Baseline, Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6. Day 1 assessment was considered as Baseline; if Day 1 was not available then the Screening assessment was considered as Baseline. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.
Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 51 104
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury (mm Hg)
Week 1 Number Analyzed 50 participants 102 participants
-0.3  (8.86) -0.7  (12.65)
Week 2 Number Analyzed 49 participants 103 participants
-2.0  (9.83) -0.2  (14.08)
Week 3 Number Analyzed 49 participants 100 participants
0.3  (12.61) -1.5  (14.05)
Week 4 Number Analyzed 50 participants 102 participants
-0.2  (13.24) -2.7  (14.37)
Week 5 Number Analyzed 47 participants 100 participants
-3.0  (12.02) -2.8  (12.57)
Week 6 Number Analyzed 46 participants 98 participants
-1.5  (13.25) -2.3  (13.62)
16.Secondary Outcome
Title Change From Baseline in Diastolic Blood Pressure
Hide Description Diastolic blood pressure was measured in sitting position at Baseline, Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6. Day 1 assessment was considered as Baseline; if Day 1 was not available then the Screening assessment was considered as Baseline. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.
Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 51 104
Mean (Standard Deviation)
Unit of Measure: mm Hg
Week 1 Number Analyzed 50 participants 102 participants
-0.3  (6.66) -0.5  (8.90)
Week 2 Number Analyzed 49 participants 103 participants
-1.1  (8.01) -0.1  (10.91)
Week 3 Number Analyzed 49 participants 100 participants
-1.0  (7.16) -1.5  (10.40)
Week 4 Number Analyzed 50 participants 102 participants
-0.9  (8.51) -1.4  (9.57)
Week 5 Number Analyzed 47 participants 100 participants
-3.0  (8.39) -1.8  (9.78)
Week 6 Number Analyzed 46 participants 98 participants
-2.2  (9.44) -1.0  (9.71)
17.Secondary Outcome
Title Change From Baseline in Pulse Rate
Hide Description Pulse rate was measured at Baseline, Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6. Day 1 assessment was considered as Baseline; if Day 1 was not available then the Screening assessment was considered as Baseline. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.
Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 51 104
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Week 1 Number Analyzed 50 participants 102 participants
-0.5  (6.88) 0.2  (8.54)
Week 2 Number Analyzed 49 participants 103 participants
-2.2  (9.23) 0.2  (9.54)
Week 3 Number Analyzed 49 participants 100 participants
1.6  (10.31) 0.2  (8.79)
Week 4 Number Analyzed 50 participants 102 participants
-0.1  (7.32) 0.8  (8.52)
Week 5 Number Analyzed 47 participants 100 participants
0.0  (9.06) 0.0  (7.32)
Week 6 Number Analyzed 46 participants 98 participants
-2.1  (8.55) 0.1  (8.06)
18.Secondary Outcome
Title Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Finding at Baseline
Hide Description Resting 12-lead ECG was obtained at Baseline. Day 1 assessment was considered as Baseline; if Day 1 was not available then the Screening assessment was considered as Baseline. ECG was also obtained when there was clinical symptom that potentially related to cardiac dysfunction based on investigator’s judgement.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 50 104
Measure Type: Number
Unit of Measure: Particpants
Normal 36 57
Abnormal, not clinically significant 14 43
Abnormal, clinically significant 0 4
19.Secondary Outcome
Title Number of Participants With a Change From Baseline in Visual Acuity
Hide Description Visual acuity is a measure of the spatial resolution of the visual processing system. Acuity is a measure of visual performance and is unrelated to the eyeglass prescription required to correct vision. Normal visual acuity is commonly referred to as 20/20 vision. Evaluation was done for oculus sinister (OS) for the left eye, oculus dexter (OD) for the right eye. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.
Time Frame From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 51 104
Measure Type: Number
Unit of Measure: Participants
OD 24 33
OS 22 35
20.Secondary Outcome
Title Number of Participants With the Indicated Grading of Myelofibrosis Using Bone Marrow Biopsy at Screening
Hide Description Bone marrow biopsy was performed at Screening and then obtained when clinically indicated. Whenever a peripheral blood smear confirmed the presence of immature or dysplastic cells, a bone marrow examination was performed. Myelofibrosis (MF) was graded from Grade MF-0 to MF-3 where MF-0=scattered linear reticulin with no intersections (cross-overs) corresponding to normal bone marrow; MF-1=loose network of reticulin with many intersections; especially in perivascular areas; MF-2=diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen and/or focal osteosclerosis; MF-3=diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis.
Time Frame Screening
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description:
Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Participants initially received eltrombopag 25 mg QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
Overall Number of Participants Analyzed 51 102
Measure Type: Number
Unit of Measure: Participants
MF Score 0 38 83
MF Score 1 13 19
MF Score 2 0 0
MF Score 3 0 0
21.Secondary Outcome
Title Pharmacokinetic (PK) Assessments for Eltrombopag for Apparent Volume of Distribution of Central Compartment (Vc/F), Apparent Volume of Distribution of Peripheral Compartment (Vp/F)
Hide Description Vc/F is apparent volume of distribution of plasma (VDP) in central compartment and Vp/F is apparent VDP in peripheral compartment. PK assessments were made with one group of serial sampling [Samples collected at pre-dose and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 24 hr post-dose] and one group of sparse assessment [Samples collected at pre-dose, between 2 to 4 hr and 5 to 8 hr post-dose]. Pre-dose samples were collected within 2 hr prior to dosing, all other samples were collected within 10 minutes(min) for samples collected between 1 and 6 hrs and within 30 mins for samples collected at 8 and 24 hr. PK analysis was conducted using a population approach with non-linear mixed effects modeling methods. Point estimates of population PK parameters are presented.
Time Frame From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population: all participants with evaluable dosing, actual sampling time, and eltrombopag concentration data.
Arm/Group Title Eltrombopag
Hide Arm/Group Description:
In Stage 1, Participants were given placebo QD for 8 weeks or were initially treated with 25 mg eltrombopag. Dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks based on weekly platelet counts. In Stage 2, participants who received eltrombopag in Stage 1 continued with the same dose of eltrombopag unless the platelet count warranted an adjustment. Participants who received placebo in Stage 1 started 25 mg eltrombopag once daily as the initial dose and was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks on based on weekly platelet counts.
Overall Number of Participants Analyzed 148
Geometric Mean (95% Confidence Interval)
Unit of Measure: Liters
Vc/F
8.80
(7.84 to 9.76)
Vp/F
33.6
(17.0 to 50.2)
22.Secondary Outcome
Title Pharmacokinetic Assessments for Eltrombopag for Apparent Clearance (CL/F), Apparent Inter-compartmental Clearance (Q/F)
Hide Description CL/F is defined as the apparent oral clearance from plasma and Q/F is defined as apparent intercompartmental clearance. PK assessments were made with one group of serial sampling [Samples collected at pre-dose and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 24 hr post-dose] and one group of sparse assessment [Samples collected at pre-dose, between 2 to 4 hr and 5 to 8 hr post-dose]. Pre-dose samples were collected within 2 hr prior to dosing, all other samples were collected within 10 min for samples collected between 1 and 6 hr and within 30 min for samples collected at 8 and 24 hr. PK analysis was conducted using a population approach with non-linear mixed effects modeling methods. Point estimates of population PK parameters are presented.
Time Frame From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Eltrombopag
Hide Arm/Group Description:
In Stage 1, Participants were given placebo QD for 8 weeks or were initially treated with 25 mg eltrombopag. Dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks based on weekly platelet counts. In Stage 2, participants who received eltrombopag in Stage 1 continued with the same dose of eltrombopag unless the platelet count warranted an adjustment. Participants who received placebo in Stage 1 started 25 mg eltrombopag once daily as the initial dose and was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks on based on weekly platelet counts.
Overall Number of Participants Analyzed 148
Geometric Mean (95% Confidence Interval)
Unit of Measure: Liters per hour(L/hr)
CL/F
0.370
(0.336 to 0.404)
Q/F
0.561
(0.444 to 0.678)
23.Secondary Outcome
Title Pharmacokinetic Assessments for Eltrombopag for Absorption Rate Constant (Ka)
Hide Description Ka is defined as the absorption rate constant. PK assessments were made with one group of serial sampling [Samples collected at pre-dose and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 24 hr post-dose] and one group of sparse assessment [Samples collected at pre-dose, between 2 to 4 hr and 5 to 8 hr post-dose]. Pre-dose samples were collected within 2 hrs prior to dosing, all other samples were collected within 10 min for samples collected between 1 and 6 hrs and within 30 mins for samples collected at 8 and 24 hr. PK analysis was conducted using a population approach with non-linear mixed effects modeling methods. Point estimates of population PK parameter is presented.
Time Frame From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Eltrombopag
Hide Arm/Group Description:
In Stage 1, Participants were given placebo QD for 8 weeks or were initially treated with 25 mg eltrombopag. Dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks based on weekly platelet counts. In Stage 2, participants who received eltrombopag in Stage 1 continued with the same dose of eltrombopag unless the platelet count warranted an adjustment. Participants who received placebo in Stage 1 started 25 mg eltrombopag once daily as the initial dose and was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks on based on weekly platelet counts.
Overall Number of Participants Analyzed 148
Geometric Mean (95% Confidence Interval)
Unit of Measure: Per hour (1/hr)
1.58
(1.05 to 2.11)
24.Secondary Outcome
Title Pharmacokinetic Assessments for Eltrombopag for Absorption Lag Time (ALAG)
Hide Description Absorption lag time (ALAG) is defined as the time taken for a drug to appear in the systemic circulation following administration. PK assessments were made with one group of serial sampling [Samples collected at pre-dose and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 24 hr post-dose] and one group of sparse assessment [Samples collected at pre-dose, between 2 to 4 hrs and 5 to 8 hrs post-dose]. Pre-dose samples were collected within 2 hrs prior to dosing, all other samples were collected within 10 min for samples collected between 1 and 6 hr and within 30 min for samples collected at 8 and 24 hr. PK analysis was conducted using a population approach with non-linear mixed effects modeling methods. Point estimates of population PK parameter is presented.
Time Frame From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Eltrombopag
Hide Arm/Group Description:
In Stage 1, Participants were given placebo QD for 8 weeks or were initially treated with 25 mg eltrombopag. Dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks based on weekly platelet counts. In Stage 2, participants who received eltrombopag in Stage 1 continued with the same dose of eltrombopag unless the platelet count warranted an adjustment. Participants who received placebo in Stage 1 started 25 mg eltrombopag once daily as the initial dose and was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks on based on weekly platelet counts.
Overall Number of Participants Analyzed 148
Geometric Mean (95% Confidence Interval)
Unit of Measure: Hour
0.855
(0.816 to 0.894)
25.Secondary Outcome
Title Post-hoc Estimates of Plasma Eltrombopag Area Under the Concentration-time Curve Over a Dosing Interval (AUC[0-tau]) After 50 mg Once Daily Dose of Eltrombopag
Hide Description AUC[0-tau] is defined as area under the concentration-time curve over a dosing interval (24 hr) of Eltrombopag atsteady-state after 50 mg once daily dose of eltrombopag. PK analysis was conducted using a population approach with non-linear mixed effects modeling methods. Post-hoc estimates of steady-state eltrombopag was determined based on the final PK model. Individual PK parameters were derived from the final PK model by an empirical Bayes estimation. Summary of steady-state AUC(0-tau) of eltrombopag is presented here.
Time Frame From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Eltrombopag
Hide Arm/Group Description:
In Stage 1, Participants were given placebo QD for 8 weeks or were initially treated with 25 mg eltrombopag. Dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks based on weekly platelet counts. In Stage 2, participants who received eltrombopag in Stage 1 continued with the same dose of eltrombopag unless the platelet count warranted an adjustment. Participants who received placebo in Stage 1 started 25 mg eltrombopag once daily as the initial dose and was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks on based on weekly platelet counts.
Overall Number of Participants Analyzed 148
Geometric Mean (95% Confidence Interval)
Unit of Measure: Microgram* hour per milliliter(μg.hr/mL)
88.8
(78.0 to 101)
26.Secondary Outcome
Title Post-hoc Estimates of Maximum Observed Concentration (Cmax) for Eltrombopag After 50 mg Once Daily Dose of Eltrombopag
Hide Description Cmax is defined as maximum observed concentration after 50 mg once daily dose of eltrombopag. PK analysis was conducted using a population approach with non-linear mixed effects modeling methods. Post-hoc estimates of steady-state eltrombopag Cmax was determined based on the final PK model. Individual PK parameters were derived from the final PK model by an empirical Bayes estimation. Summary of steady-state Cmax of eltrombopag .is presented here.
Time Frame From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Eltrombopag
Hide Arm/Group Description:
In Stage 1, Participants were given placebo QD for 8 weeks or were initially treated with 25 mg eltrombopag. Dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks based on weekly platelet counts. In Stage 2, participants who received eltrombopag in Stage 1 continued with the same dose of eltrombopag unless the platelet count warranted an adjustment. Participants who received placebo in Stage 1 started 25 mg eltrombopag once daily as the initial dose and was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks on based on weekly platelet counts.
Overall Number of Participants Analyzed 148
Geometric Mean (95% Confidence Interval)
Unit of Measure: Nanogram/ Milliliter (ng/mL)
6916
(6205 to 7708)
27.Secondary Outcome
Title Percentage of Participants Estimated as Responders to Eltrombopag by the Pharmacokinetic/ Pharmacodynamic Model
Hide Description Responders are participants whose SLOP estimates are larger than zero. The Pharmacokinetic/ Pharmacodynamic relationship between eltrombopag concentrations and the platelet response was described by a four-compartment life span model, representing one precursor production compartment, two transit/maturation compartments and one blood platelet compartment.
Time Frame From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Population: all participants with evaluable dosing, actual sampling time, and platelet count data.
Arm/Group Title Eltrombopag
Hide Arm/Group Description:
In Stage 1, Participants were given placebo QD for 8 weeks or were initially treated with 25 mg eltrombopag. Dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks based on weekly platelet counts. In Stage 2, participants who received eltrombopag in Stage 1 continued with the same dose of eltrombopag unless the platelet count warranted an adjustment. Participants who received placebo in Stage 1 started 25 mg eltrombopag once daily as the initial dose and was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks on based on weekly platelet counts.
Overall Number of Participants Analyzed 147
Measure Type: Number
Unit of Measure: Percentage of participants
89
28.Secondary Outcome
Title Pharmacodynamic Parameter-Linear Proportionality Constant of Drug Effect (SLOP): the Proportional Increase of Platelet Production Rate With Each 1-μg/mL Increase in Eltrombopag Plasma Concentration
Hide Description The Pharmacokinetic/ Pharmacodynamic relationship between eltrombopag concentrations and the platelet response was described by a four-compartment life span model, representing one precursor production compartment, two transit/maturation compartments and one blood platelet compartment.
Time Frame From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Population
Arm/Group Title Eltrombopag
Hide Arm/Group Description:
In Stage 1, Participants were given placebo QD for 8 weeks or were initially treated with 25 mg eltrombopag. Dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks based on weekly platelet counts. In Stage 2, participants who received eltrombopag in Stage 1 continued with the same dose of eltrombopag unless the platelet count warranted an adjustment. Participants who received placebo in Stage 1 started 25 mg eltrombopag once daily as the initial dose and was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks on based on weekly platelet counts.
Overall Number of Participants Analyzed 147
Geometric Mean (95% Confidence Interval)
Unit of Measure: Milliliter/microgram
0.860
(0.639 to 1.08)
29.Secondary Outcome
Title Pharmacodynamic Parameter- Production Rate of Platelet Precursors (KIN)
Hide Description The Pharmacokinetic/ Pharmacodynamic relationship between eltrombopag concentrations and the platelet response was described by a four-compartment life span model, representing one precursor production compartment, two transit/maturation compartments and one blood platelet compartment. The estimate of KIN was fixed to 1.43x10^9/L.hr.
Time Frame From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Population
Arm/Group Title Eltrombopag
Hide Arm/Group Description:
In Stage 1, Participants were given placebo QD for 8 weeks or were initially treated with 25 mg eltrombopag. Dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks based on weekly platelet counts. In Stage 2, participants who received eltrombopag in Stage 1 continued with the same dose of eltrombopag unless the platelet count warranted an adjustment. Participants who received placebo in Stage 1 started 25 mg eltrombopag once daily as the initial dose and was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks on based on weekly platelet counts.
Overall Number of Participants Analyzed 147
Measure Type: Number
Unit of Measure: 1 x 10^9/L.hr
1.43
30.Secondary Outcome
Title Pharmacodynamic Parameter-Maturation Rate of Platelet Precursors (KOUT)
Hide Description The Pharmacokinetic/ Pharmacodynamic relationship between eltrombopag concentrations and the platelet response was described by a four-compartment life span model, representing one precursor production compartment, two transit/maturation compartments and one blood platelet compartment. The estimate of KOUT was fixed to 0.0253 /hr.
Time Frame From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK/PD Population
Arm/Group Title Eltrombopag
Hide Arm/Group Description:
In Stage 1, Participants were given placebo QD for 8 weeks or were initially treated with 25 mg eltrombopag. Dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks based on weekly platelet counts. In Stage 2, participants who received eltrombopag in Stage 1 continued with the same dose of eltrombopag unless the platelet count warranted an adjustment. Participants who received placebo in Stage 1 started 25 mg eltrombopag once daily as the initial dose and was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for period of 8 weeks on based on weekly platelet counts.
Overall Number of Participants Analyzed 147
Measure Type: Number
Unit of Measure: 1/ hr
0.0253
Time Frame On-therapy (+1 Day) serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product and up to the day after the last dose of investigational product (up to the eighth week.
Adverse Event Reporting Description On-therapy(+1 Day) SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of randomized study treatment.
 
Arm/Group Title Placebo Eltrombopag
Hide Arm/Group Description Participants initially received placebo QD. Based on weekly platelet counts, the dose of placebo was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks. Participants initially received eltrombopag 25 milligrams (mg) QD. Based on weekly platelet counts, the dose of eltrombopag was adjusted to maintain platelet counts between 50×10^9/L and 250×10^9/L for a period of 8 weeks.
All-Cause Mortality
Placebo Eltrombopag
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Eltrombopag
Affected / at Risk (%) Affected / at Risk (%)
Total   5/51 (9.80%)   5/104 (4.81%) 
Blood and lymphatic system disorders     
Thrombocytopenia  1  1/51 (1.96%)  0/104 (0.00%) 
Eye disorders     
Lenticular opacities  1  1/51 (1.96%)  0/104 (0.00%) 
Retinopathy  1  0/51 (0.00%)  1/104 (0.96%) 
General disorders     
Death  1  1/51 (1.96%)  0/104 (0.00%) 
Infections and infestations     
Respiratory tract infection  1  1/51 (1.96%)  0/104 (0.00%) 
Investigations     
Platelet count decreased  1  1/51 (1.96%)  0/104 (0.00%) 
Nervous system disorders     
Cerebral infarction  1  0/51 (0.00%)  1/104 (0.96%) 
Subarachnoid haemorrhage  1  1/51 (1.96%)  0/104 (0.00%) 
Renal and urinary disorders     
Renal failure acute  1  0/51 (0.00%)  1/104 (0.96%) 
Reproductive system and breast disorders     
Ovarian cyst ruptured  1  0/51 (0.00%)  1/104 (0.96%) 
Vascular disorders     
Deep vein thrombosis  1  0/51 (0.00%)  1/104 (0.96%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Placebo Eltrombopag
Affected / at Risk (%) Affected / at Risk (%)
Total   21/51 (41.18%)   45/104 (43.27%) 
Blood and lymphatic system disorders     
Anemia  1  3/51 (5.88%)  3/104 (2.88%) 
Infections and infestations     
Nasopharyngitis  1  5/51 (9.80%)  11/104 (10.58%) 
Upper respiratory tract infection  1  4/51 (7.84%)  7/104 (6.73%) 
Investigations     
Alanine aminotransferase increased  1  8/51 (15.69%)  9/104 (8.65%) 
Aspartate aminotransferase increased  1  5/51 (9.80%)  7/104 (6.73%) 
Blood bilirubin increased  1  0/51 (0.00%)  5/104 (4.81%) 
White blood cell count increased  1  3/51 (5.88%)  2/104 (1.92%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  8/51 (15.69%)  11/104 (10.58%) 
Nervous system disorders     
Dizziness  1  1/51 (1.96%)  4/104 (3.85%) 
Skin and subcutaneous tissue disorders     
Rash  1  2/51 (3.92%)  4/104 (3.85%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Results Point of Contact
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01762761     History of Changes
Other Study ID Numbers: 113765
First Submitted: December 19, 2012
First Posted: January 8, 2013
Results First Submitted: January 19, 2015
Results First Posted: March 9, 2015
Last Update Posted: January 15, 2019