Phase 2
N=15
Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP)
Purpura, Thrombocytopaenic, Idiopathic
Bottom Line
View on ClinicalTrials.gov: NCT00908037 ↗Enrolled (actual)
15
Serious AEs
11.0%
Results posted
Oct 2014
Primary outcome: Primary: Percentage of Participants Achieving a Platelet Count >=50 Giga Cells Per Liter (Gi/L) at Least Once, Between Day 8 and Day 43 (Weeks 1 to 6) of the Randomized Period of the Study (Part 2) — 0; 62.5; 33.3; 63.2 Percentage of Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- eltrombopag (Drug); Placebo (Drug)
- Age
- Pediatric · 1+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Feb 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving a Platelet Count >=50 Giga Cells Per Liter (Gi/L) at Least Once, Between Day 8 and Day 43 (Weeks 1 to 6) of the Randomized Period of the Study (Part 2) |
0; 62.5; 33.3; 63.2; 80.0; 60.0 | — |
| SECONDARY Percentage of Participants Achieving Platelet Counts >=50Gi/L During Treatment With Eltrombopag in >= 60% of Assessments Between Day 15 and Day 43 (Weeks 2 Through 6) of the Randomized Treatment Period (Part 2) |
0; 35.6 | — |
| SECONDARY Weighted Mean Platelet Count |
12.2; 15.5; 30.5; 68 | — |
| SECONDARY Percentage of Participants Achieving Platelet Counts >=50Gi/L at Any Time During the 24 Weeks of Eltrombopag Dosing During Part 1. |
80; 80; 60 | — |
| SECONDARY Percentage of Participants Achieving Platelet Counts >=50 Gi/L at Any Time During the 31 Weeks of Eltrombopag Treatment During Part 2/ 3. |
75.0; 82.1; 86.7 | — |
| SECONDARY Population Pharmacokinetic (PK) Assessment for Eltrombopag for AUC(0-t) During Part 1, 2, and 2/3. |
101; 132; 142 | — |
| SECONDARY Population Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax and Ct During Part 1, 2, and 2/3. |
6.65; 9.19; 10.7; 2.42; 2.95; 2.91 | — |
| SECONDARY Population Pharmacokinetic (PK) Assessments for Eltrombopag for Tmax During Part 1, 2, and 2/3 |
4.0; 4.0; 2.0 | — |
| SECONDARY Population Pharmacokinetic (PK) Assessments for Eltrombopag for CL/F During Part 1, 2, and 2/3 |
0.50; 0.38; 0.25 | — |
| SECONDARY Maximum Duration for Which a Participant Continuously Maintained a Platelet Count of >=50 Gi/L During the 7 Weeks of Eltrombopag Treatment in Part 2 |
0.0; 1.0; 0.0; 2.0; 1.0; 1.0 | — |
| SECONDARY Maximum Duration for Which a Participant Continuously Maintained a Platelet Count of >=50 Gi/L During the 24 Weeks of Eltrombopag Treatment in Part 2/ 3 |
2.0; 8.0; 4.0 | — |
| SECONDARY Percentage of Participants Who Reduced or Discontinued Baseline Concomitant Idiopathic Thrombocytopenic Purpura (ITP) Medications During the 24 Weeks of Eltrombopag Treatment During Part 1. |
0; 20.0; 0; 0; 100.0; 0 | — |
| SECONDARY Percentage of Participants Who Reduced or Discontinued Baseline Concomitant ITP Medications During the 24 Weeks of Eltrombopag Treatment During Part 2/ 3 |
25.0; 17.9; 13.3; 66.7; 20.0; 100.0 | — |
| SECONDARY Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 2/3 |
8; 4; 4; 1; 0; 0 | — |
| SECONDARY Kids' ITP Tool (KIT) Questionnaire Total Score at Baseline, Week 6, Week 12, and Week 24 as Assessed Using the KIT Questionnaire During the Dose Finding Period, Part 1 |
73.18; 53.95; 74.80; 82.84; 61.57; 71.54 | — |
| SECONDARY Kids' ITP Tool (KIT) Questionnaire Total Score at Baseline and Week 6as Assessed Using the KIT Questionnaire During the Randomized Period, Part 2 |
83.94; 76.84; 71.05; 66.36; 82.61; 78.23 | — |
| SECONDARY Kids' ITP Tools (KIT) Questionnaire Total Score at Baseline, Week, 6, Week 12, and End of Treatment Visit as Assessed Using the KIT Questionnaire During the Eltrombopag Open-Label Period, Part 2/3 |
79.34; 70.59; 79.10; 79.46; 80.16; 80.85 | — |
| SECONDARY Number of Participants With Any Bleeding, no Clinically Significant Bleeding and Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale During Part 2 |
6; 16; 7; 11; 5; 8 | — |
| SECONDARY Number of Participants With Any Bleeding, no Clinically Significant Bleeding and Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale During Part 2/3 |
23; 18; 12; 17; 25; 9 | — |
| SECONDARY Number of Participants With the Indicated Clinical Chemistry Parameter Falling Outside of the Reference Range Any Time Post-Baseline During Part 1, Part 2, and Part 2/3 |
5; 4; 7; 17; 1; 1 | — |
| SECONDARY Number of Participants With the Indicated Hematology Parameters Falling Outside of the Reference Range at Any Time Post-Baseline During Part 1, Part 2, and Part 2/3 |
5; 0; 7; 15; 2; 8 | — |
| SECONDARY Number of Participants With the Indicated Renal Parameters Falling Outside of the Reference Range Any Time Post-Baseline During Part 1, Part 2, and Part 2/3 |
1; 3; 6; 13; 5; 4 | — |
| SECONDARY Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 1 |
0; 0; 2; 0; 0; 0 | — |
| SECONDARY Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2 |
0; 2; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2/3 |
3; 0; 1; 1; 0; 0 | — |
| SECONDARY Number of Participants With the Indicated Vital Signs Falling Outside of the Reference Range During Part 1, Part 2, and Part 2/3 |
1; 4; 3; 3; 0; 2 | — |
| SECONDARY Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Dose-Finding Period, Part 1 |
20.0; 21.4; 25.5; 21.5; 22.0; 26.5 | — |
| SECONDARY Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Randomized Period, Part 2 |
19.6; 18.4; 19.4; 21.5; 18.7; 21.4 | — |
| SECONDARY Mean Respiratory Rate at Baseline and Maximum Post-Baseline Visit During Part 2/3 |
18.5; 21.2; 21.5; 19.2; 2.12; 21.7 | — |
| SECONDARY Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Dose-Finding Period, Part 1 |
85.2; 88.4; 102.0; 84.3; 88.2; 102.4 | — |
| SECONDARY Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Randomized Period, Part 2 |
80.1; 82.8; 86.9; 94.3; 91.5; 101.5 | — |
| SECONDARY Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Eltrombopag Only Period Part 2/3 |
82.8; 94.3; 104.8; 78.7; 92.0; 100.8 | — |
| SECONDARY Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 24 During the Dose-Finding Period, Part 1 |
1; 0; 0; 2; 0; 0 | — |
| SECONDARY Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 7 During the Randomized Period,Part 2 |
2; 0; 0; 1; 7; 8 | — |
| SECONDARY Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 24 During the Eltrombopag Open-label Period, Part 2/3 |
0; 1; 10; 0; 0; 0 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 1 |
5; 5; 5; 1; 1; 0 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2 |
8; 13; 9; 14; 3; 9 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2/3 |
22; 26; 14; 3; 5; 0 | — |
| SECONDARY Number of Participants With a Change in Visual Acuity and a Change Due to Worsening of Cataracts During Part 1 |
1; 1; 2; 0; 0; 1 | — |
| SECONDARY Number of Participants With a Change in Visual Acuity and a Change Due to Worsening of Cataracts |
13; 17; 9; 4; 1; 2 | — |
Summary
Phase II, multi-center, 3 part, staggered cohort, open-label and double blind, randomized, placebo controlled study involving 3 age-determined cohorts (Cohort 1: between 12 and 17 years old; Cohort 2: between 6 and 11 years old; Cohort 3: between 1 and 5 years old). Daily dosing with eltrombopag will begin with 5 patients in the oldest age cohort in an open label fashion, and a review of safety, pharmacokinetic and platelet count data will be performed regularly. If no safety concerns are identified after 12 weeks, 18 additional patients will be randomised to placebo or eltrombopag (2:1 randomisation). After 7 weeks of randomized treatment, all patients will receive eltrombopag in an open label fashion. The total duration of treatment with eltrombopag will be 24 weeks. If at the time of the aforementioned 12 week review of the first 5 patients no safety issues are identified, dosing will begin in the next lower age cohort with an initial group of 5 patients. The same procedure will be followed in terms of safety review and subsequent enrolment and randomisation of the additional patients. Initiation of the younger age cohort will take place once data from the previous has been evaluated. Doses will be adjusted according to platelet counts and tolerability. The study will include a review of the safety data by a Data Safety Monitoring Board.
Eligibility Criteria
Inclusion Criteria
- Subjects between 1 year and 3 consecutive days within 2 weeks of Day 1.
- Subjects who have previously received eltrombopag or any other thrombopoietin receptor agonist.
- For female subjects who have reached menarche status, an inability or unwillingness to provide a blood or urine specimen for pregnancy testing.
- Female subjects who are pregnant or lactating.
Data sourced from ClinicalTrials.gov (NCT00908037). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.