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Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP) (PETIT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00908037
First received: May 21, 2009
Last updated: October 30, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Purpura, Thrombocytopaenic, Idiopathic
Drug: eltrombopag
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Three Part, Staggered Cohort, Open-label and Double Blind, Randomized, Placebo Controlled Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of Eltrombopag, a Thrombopoietin Receptor Agonist, in Previously Treated Pediatric Patients With Chronic ITP.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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) [ Time Frame: From Day 8 up to Day 43 of Part 2 ] [ Designated as safety issue: No ]
    Participants who achieved a platelet count >=50 Gi/L at least once between Day 8 and Day 43 (first 6 weeks of Part 2) in the absense of rescue treatment were reported. A 95% confidence interval was calculated by the exact binomial method.


Secondary Outcome Measures:
  • 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) [ Time Frame: Between Day 15 and Day 43 of Part 2 ] [ Designated as safety issue: No ]
    Sustained platelet response between the treatment groups was assessed by determining the number of participants who achieved a platelet count >=50 Gi/L during treatment with eltrombopag in >= 60% of assessments between Day 15 and Day 43 in the absence of rescue treatment were reported here.

  • Weighted Mean Platelet Count [ Time Frame: Baseline and Day 43 of Part 2 ] [ Designated as safety issue: No ]
    The weighted mean platelet count is defined as the area under the platelet-time curve divided by the duration of the treatment (12 weeks). Based on the Analysis of Covariance (ANCOVA) model, the weighted mean platelet count is the sum of the Baseline count plus the age cohort plus the treatment. Baseline was defined as the platelet count taken on Day 1 or within 48 hours prior to the first dose of treatment.

  • Percentage of Participants Achieving Platelet Counts >=50Gi/L at Any Time During the 24 Weeks of Eltrombopag Dosing During Part 1. [ Time Frame: From Day 1 of treatment up to Week 24 of Part 1 ] [ Designated as safety issue: No ]
    The percentage of participants achieving platelet counts >=50Gi/L at least once at any time during the 24 weeks of eltrombopag treatment were reported.

  • Percentage of Participants Achieving Platelet Counts >=50 Gi/L at Any Time During the 31 Weeks of Eltrombopag Treatment During Part 2/ 3. [ Time Frame: Part 2/3 up to Study Week 31 ] [ Designated as safety issue: No ]
    The percentage of participants achieving platelet counts >=50Gi/L at least once at any time during the 24 weeks of eltrombopag treatment during Part 2/3 of the study were reported. Participants randmoized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.

  • Population Pharmacokinetic (PK) Assessment for Eltrombopag for AUC(0-t) During Part 1, 2, and 2/3. [ Time Frame: From Day 1 of treatment up to Study Week 31 ] [ Designated as safety issue: No ]
    The area under the concentration-time curve over the dosing interval (AUC0-t) data was collected to estimate primary model-based PK parameters. PK samples were collected within 3 hours prior to dosing and 2, 4, 6, 8 and 24 hours after dosing. Doses were normalized to 50mg for comparison. PK samples were collected at each on-treatment visit during Part 1, Part 2, and Part 2/3. The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. AUC(0-t) is defined as the area under the concentration-time curve over the dosing interval. From the final model, a single value of AUC(0-t) was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.

  • Population Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax and Ct During Part 1, 2, and 2/3. [ Time Frame: From Day 1 of treatment up to Study Week 31 ] [ Designated as safety issue: No ]
    The maximum observed concentration (Cmax) and the concentration at the end of the dosing interval (Ct) data were collected to estimate primary model-based PK parameters. PK samples were collected within 3 hours prior to dosing and 2, 4, 6, 8 and 24 hours after dosing. Doses were normalized to 50mg for comparison. PK samples were collected at each on-treatment visit during Part 1, Part 2, and Part 2/3. The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. From the final model, a single value of Cmax and Ct were estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.

  • Population Pharmacokinetic (PK) Assessments for Eltrombopag for Tmax During Part 1, 2, and 2/3 [ Time Frame: From Day 1 of treatment up to Study Week 31 ] [ Designated as safety issue: No ]
    The time to maximum concentration (tmax) was collected to estimate primary model-based PK parameters. PK samples were collected within 3 hours prior to dosing and 2, 4, 6, 8 and 24 hours after dosing. PK samples were collected at each on-treatment visit during Part 1, Part 2, and Part 2/3. The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. From the final model, a single value of tmax was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.

  • Population Pharmacokinetic (PK) Assessments for Eltrombopag for CL/F During Part 1, 2, and 2/3 [ Time Frame: From Day 1 of treatment up to Study Week 31 ] [ Designated as safety issue: No ]
    The apparent plasma clearance following oral dosing of eltrombopag (CL/F) was collected to estimate primary model-based PK parameters. PK samples were collected within 3 hours prior to dosing and 2, 4, 6, 8 and 24 hours after dosing. PK samples were collected at each on-treatment visit during Part 1, Part 2, and Part 2/3. The concentration data were pooled across visits to identify population PK and variability parameter estimates and covariate effects. From the final model, a single value of CL/F was estimated for each subject, and geometric mean (95% CI) values are presented for each cohort for a 50mg dose.

  • 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 [ Time Frame: From Baseline through Week 7 of Part 2 ] [ Designated as safety issue: No ]
    The maximum duration for which a participant continuously maintained a platelet count >=50 Gi/L in the absence of rescue treatment was calculated and summarized during the 24 weeks of eltrombopag treatment in Part 2. Participants with non-weekly assessments were assumed to have maintained a positive response for each week between two assessments that had positive responses. If a particpant achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the participant had achieved a positive response for one day. Excludes periods from initiation of rescue medication until platelet count falls to below 50Gi/L, irrespective of platelet count

  • 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 [ Time Frame: From Baseline up to Study Week 31 ] [ Designated as safety issue: No ]
    The maximum duration for which a participant continuously maintained a platelet count >=50 Gi/L in the absence of rescue treatment was calculated and summarized during the 24 weeks of eltrombopag treatment in Part 2/3. Participants with non-weekly assessments were assumed to have maintained a positive response for each week between two assessments that had positive responses. If a particpant achieved a positive response at an assessment and then achieved a negative response at the next assessment, then it was assumed that the participant had achieved a positive response for one day. Participants randmoized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.

  • Percentage of Participants Who Reduced or Discontinued Baseline Concomitant Idiopathic Thrombocytopenic Purpura (ITP) Medications During the 24 Weeks of Eltrombopag Treatment During Part 1. [ Time Frame: From Baseline up to Week 24+ 1 day of Part 1 ] [ Designated as safety issue: No ]
    The participants who discontinued (dis) or had a sustained reduction (red) of a Baseline (BL) ITP medication for at least one day during the period of Day 1 of Part 1 to the last dose of study medication +1 day are reported. The denominator is the number of subjects taking an ITP medication at baseline. For participants in Part 1, Baseline is defined as Day 1 of Part 1. A sustained reduction is defined as reduction for 4 weeks or more. An attempted red or dis is a decrease in the dose or frequency from the BL dose or frequency of an ITP medication for at least one day during the period Part 1 Day 1 to the last dose of study medication + 1 day.

  • Percentage of Participants Who Reduced or Discontinued Baseline Concomitant ITP Medications During the 24 Weeks of Eltrombopag Treatment During Part 2/ 3 [ Time Frame: From Baseline to the end of treatment up to Week 31 + 1 day of Part 2/3 ] [ Designated as safety issue: No ]
    Participants who discontinued (dis) or had a sustained reduction (red) of a Baseline (BL) ITP medication for at least one day during the period of Day 1 of Part 2/3 to the last dose of study medication +1 day are reported. The denominator is the number of subjects taking an ITP medication at baseline. For participants randomized to placebo in Part 2, BL is defined as Week 7 of Part 2. For participants randomized to eltrombopag in Part 2, BL is defined as Day 1 of Part 2. A sustained reduction is defined as reduction for 4 weeks or more. An attempted reduction or discontinuation is a decrease in the dose or frequency from the BL dose or frequency of an ITP medication for at least one day during the period Part 2/3 Day 1 to the last dose of study medication + 1 day.

  • Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 2/3 [ Time Frame: From Baseline to the end of treatment up to Week 31 + 1 day of Part2/3 ] [ Designated as safety issue: No ]
    Rescue treatment was defined as either a new immune (idiopathic) thrombocytopenic purpura (ITP) medication, an increase in the dose of a concomitant ITP medication from Baseline, a platelet transfusion, or a splenectomy. For particpants randomized to placebo in Part 2, Baseline is defined as Week 7 of Part 2. For participants randomized to eltrombopag in Part 2, Baseline is defined as Day 1 of Part 2. Participants randmoized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.

  • 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 [ Time Frame: Baseline, Week 6, Week 12, and Week 24 of Part 1 ] [ Designated as safety issue: No ]
    The KIT questionnaire measures the impact on the quality of life determined by the participant and the guardian by self reported outcomes at Baseline or the Screening Visit, after 6 weeks of treatment, after 12 weeks of treatment and at the end of treatment or withdrawal from the study. The KIT total score is calculated from the scores of each of the individual questions from Q1 - Q26 (excluding any answer that is 'Not applicable'). The code list used for the individual question scores is: 1 = never, 2 = seldom, 3 = sometimes, 4 = often, 5 = always and 9 = not applicable. The range of values the total score can take is 0 (worst) to 100 (best). For subjects under the age of six, the family questionnaire (parental proxy) has been used.

  • Kids' ITP Tool (KIT) Questionnaire Total Score at Baseline and Week 6as Assessed Using the KIT Questionnaire During the Randomized Period, Part 2 [ Time Frame: Baseline and Week 6 of Part 2 ] [ Designated as safety issue: No ]
    The KIT questionnaire measures the impact on the quality of life determined by the participant and the guardian by self reported outcomes at Baseline or the Screening Visit, after 6 weeks of treatment or withdrawal from the study. The KIT total score is calculated from the scores of each of the individual questions from Q1 - Q26 (excluding any answer that is 'Not applicable'). The code list used for the individual question scores is: 1 = never, 2 = seldom, 3 = sometimes, 4 = often, 5 = always and 9 = not applicable. The range of values the total score can take is 0 (worst) to 100 (best). For subjects under the age of six, the family questionnaire (parental proxy) has been used.

  • 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 [ Time Frame: From Baseline to end of treatment up to Study Week 31 ] [ Designated as safety issue: No ]
    The KIT questionnaire measures the impact on the quality of life determined by the participant and the guardian by self reported outcomes at Baseline or the Screening Visit, after 6 weeks of treatment, after 12 weeks of treatment and at the end of treatment or withdrawal from the study. The KIT total score is calculated from the scores of each of the individual questions from Q1 - Q26 (excluding any answer that is 'Not applicable'). The code list used for the individual question scores is: 1=never, 2=seldom, 3=sometimes, 4=often, 5=always and 9=not applicable. The range of values the total score can take is 0 (worst) to 100 (best). For subjects under the age of six, the family questionnaire (parental proxy) has been used.

  • 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 [ Time Frame: From Baseline through Week 7 of Part 2 ] [ Designated as safety issue: No ]
    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 bleeding and Grade 4 = debilitating blood loss. The WHO grades were dichotomized into the following categories: no bleeding=Grade 0; any bleeding=Grades 1 to 4; no clinically significant bleeding=Grades 0 to 1; clinically significant bleeding=Grades 2 to 4. For participants randomized to Placebo in Part 2, Baseline defined as Week 7 of Part 2. For participants randomized to Eltrombopag in Part 2, Baseline defined as Day 1 of Part 2.

  • 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 [ Time Frame: From Baseline of Part 2/3 through Follow-up ] [ Designated as safety issue: No ]
    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 bleeding and Grade 4 = debilitating blood loss. The WHO grades were dichotomized into the following categories: no bleeding=Grade 0; any bleeding=Grades 1 to 4; no clinically significant bleeding=Grades 0 to 1; clinically significant bleeding=Grades 2 to 4. For participants randomized to Placebo in Part 2, Baseline defined as Week 7 of Part 2. For participants randomized to Eltrombopag in Part 2, Baseline defined as Day 1 of Part 2.

  • 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 [ Time Frame: Post-Baseline from Week 1 through Follow-up up to Study Week 35 ] [ Designated as safety issue: No ]
    Clinical chemistry parameters included: aspartate amino transferase (AST, reference range [RR]: 0-38 International Units per Liter [IU/L]), alkaline phosphatase (ALP: RR: 50 - 375 IU/L), total bilirubin (RR: 3.42 - 22.23 micromoles [umol]/L), albumin grams [g/L], alanine amino transferase (ALT, RR: 5-30 IU/L), prothrombin international normalized ratio (PT INR, RR-0.9 - 1.2), activated partial thromboplastin time (APTT, RR: 24.2 - 32.9 seconds), glucose (RR: 4.107- 6.55018 millimoles [mmol]/L), potassium (3 - 5 mmol/L), and sodium (135 - 143 mmol/L). Baseline values were obtained at Day 1. The number of participants with the indicated clinical chemistry data outside of the reference range (with high and low) any time post-Baseline are presented. Anytime post-Baseline assesments included any scheduled and unscheduled post-Baseline assessment

  • 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 [ Time Frame: Post-Baseline from Week 1 through Follow-up up to Study Week 35 ] [ Designated as safety issue: No ]
    Hematology parameters included: erythrocytes (RR: 4.2 - 6.1 teragrams per liter [TI/L]), hemoglobin (RR: 125 - 165 g/L), hematocrit (RR: 0.36 - 0.46), platelets (RR: 170 - 430 gigagrams per liter [GI/L]), mean platelet volume (MPV, RR: 4 - 14 femotoliter [fL]), leukocytes (RR: 3.4 - 11.2 GI/L), total neutrophils (RR: 2.1 - 4.9 GI/L), lymphocytes (RR: 1.4 - 2.9 GI/L), monocytes (RR: 0.2 - 0.9 GI/L), eosinophils (RR: 0.2 - 0.7 GI/L), and basophils (RR: 0.02 - 0.12 GI/L). Baseline values were obtained at Day 1. The number of participants with the indicated hematology parameters data outside of the reference range (with high and low) any time post-baseline are presented. Anytime post-Baseline assesments included any scheduled and unscheduled post-Baseline assessment

  • 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 [ Time Frame: Post-Baseline from Week 1 through Follow-up up to Study Week 35 ] [ Designated as safety issue: No ]
    Renal parameters included: creatinine (RR: 44.2 - 88.4 umol/L), creatinine clearance derived (RR: 89.0 - 165.0 milliliter per minute [ ml/min]), protein/creatinine (RR: 0.113- 18.0992 microgram per millimoles [mg/mmol]), and urea (RR: 1.785- 8.925 mmol/L). Baseline values were obtained at Day 1. The number of participants with the indicated renal parameters data outside the reference range (with high and low) any time post-Baseline are presented. Anytime post-Baseline assesments included any scheduled and unscheduled post-baseline assessment

  • Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 1 [ Time Frame: From Baseline up to Study Week 24 of Part 1 ] [ Designated as safety issue: No ]
    Urine microscopy included Red Blood Cell (RBC) casts, white blood cell (WBC) casts, and epithelial renal tubular cell casts. Urine microscopy data was reviewed by the Medical Monitor in order to classify the results as positive or negative. The number of participants with a positive result at any time post Baseline were reported. A positive result indicated if the result was positive for at least one of RBC casts, WBC casts, or epithelial renal tubular cell casts.

  • Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2 [ Time Frame: From Baseline and post-Baseline up to Study Week 7 of Part 2 ] [ Designated as safety issue: No ]
    Urine microscopy included Red Blood Cell (RBC) casts, white blood cell (WBC) casts, and epithelial renal tubular cell casts. Urine microscopy data was reviewed by the Medical Monitor in order to classify the results as positive or negative. The nmber of participants with positive finding at Baseline and at anytime post-Baseline (Post-BL) were reported. Baseline was defined as the value obtained at the first visit before treatment (Pre-trt). A positive result indicated if the result was positive for at least one of RBC casts, WBC casts, or epithelial renal tubular cell casts.

  • Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2/3 [ Time Frame: From Baseline and post-Baseline up to Study Week 31 of Part 2/3 ] [ Designated as safety issue: No ]
    Urine microscopy included Red Blood Cell (RBC) casts, white blood cell (WBC) casts, and epithelial renal tubular cell casts. Urine microscopy data was reviewed by the Medical Monitor in order to classify the results as positive or negative. The number of participants with positive finding at Baseline and at anytime post-Baseline (Post-BL) were reported. Baseline was defined as the value obtained at the first visit before treatment (Pre-trt). A positive result indicated if the result was positive for at least one of RBC casts, WBC casts, or epithelial renal tubular cell casts. Participants randomized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.

  • Number of Participants With the Indicated Vital Signs Falling Outside of the Reference Range During Part 1, Part 2, and Part 2/3 [ Time Frame: From Baseline through Study Week 35 ] [ Designated as safety issue: No ]
    Vital sign assessments included systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements that were measured before any blood draw at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, at each Follow-up week (Week 1-4) and the maximum post- Baseline (BL) visit. BL is defined as the value obtained on Day 1of treatment. The maximum post-BL visit (MPB) included any scheduled and unscheduled post-BL assessment. Reference ranges (RR) for SBP (mmHg) (Lower limit of normal, normal, Upper limit of normal) for Cohort 1: <85, 85-115, >115; for Cohort 2: <85, 85-120,>120; and Cohort 3: <95, 95-135, >135. RR for DBP (mmHg) for Cohort 1: <45, 45-70,>70; for Cohort 2: <50, 50-75, >75; and Cohort 3: <55, 55-85, >85.

  • Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Dose-Finding Period, Part 1 [ Time Frame: From Baseline through Week 24 ] [ Designated as safety issue: No ]
    Respiratory rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline value included any scheduled and unscheduled post-Baseline assessment.

  • Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Randomized Period, Part 2 [ Time Frame: From Week 1 to Week 7 of Part 2 ] [ Designated as safety issue: No ]
    Respiratory rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline value included any scheduled and unscheduled post-Baseline assessment.

  • Mean Respiratory Rate at Baseline and Maximum Post-Baseline Visit During Part 2/3 [ Time Frame: From Week 1 to Follow-up Week 4 of Part 2/3 up to Study Week 35 ] [ Designated as safety issue: No ]
    Respiratory rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline visit included any scheduled and unscheduled post-Baseline assessment. Participants randomized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.

  • Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Dose-Finding Period, Part 1 [ Time Frame: From Week 1 to Follow-up Week 4 of Part 1, up to Study Week 28 ] [ Designated as safety issue: No ]
    Pulse rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline (MPB) visit included any scheduled and unscheduled post-Baseline assessment..

  • Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Randomized Period, Part 2 [ Time Frame: From Week 1 to Week 7 of Part 2 ] [ Designated as safety issue: No ]
    Pulse rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline visit included any scheduled and unscheduled post-Baseline assessment.

  • Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Eltrombopag Only Period Part 2/3 [ Time Frame: From Week 1to Follow-up Week 4 of Part 2/3, up to Study Week 35 ] [ Designated as safety issue: No ]
    Pulse rate was measured at the following scheduled time points: Screening, Day 1, each week from Week 1 to Week 24, and at each Follow-up Weeks 1-4. Baseline is defined as the value obtained on Day 1 of treatment. The maximum post-Baseline visit included any scheduled and unscheduled post-Baseline assessment. Participants randomized to receive eltrombopag for 7 weeks in Part 2 continued receiving eltrombopag for an additional 17 weeks in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 24. Participants randomized to receive placebo for 7 weeks in Part 2, received 24 weeks of eltrombopag in Part 2/3 (for a total of 24 weeks of treatment) up to Study Week 31.

  • Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 24 During the Dose-Finding Period, Part 1 [ Time Frame: Baseline and Week 24 of Part 1 ] [ Designated as safety issue: No ]
    Urinalysis parameters included: urine protein (UP), urine glucose (UG), urine ketones (UK), urine occult blood (UOB), and pH. The dipstick test gives results in a semi-quantitative manner. UP was categorized as missing (MS), no result (NR), negative (Neg), Trace, 1+, 2+, 3+ and 4+. UG results were categorized as MS, NR, Neg, normal, 5, 15(1+), 30(2+), 60(3+), 110(4+)UK parameters were categorized as as MS, NR, Neg, Trace(5), Small(15), Moderate(40), Large(80), Large(160). UOB parameters were categorized as MS, NR, Neg, 1+, 2+, 3+, Non haemolysed trace, and haemolysed trace. PH results were categorized as MS. NR, normalresult, Neg, and range of pH (from 5-9in increments of 0.5). Data for indicated parameters was reported at Baseline (BL) and Week 24 (W24). The Baseline value was the measurement taken at Day 1.

  • Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 7 During the Randomized Period,Part 2 [ Time Frame: Baseline and Week 7 of Part 2 ] [ Designated as safety issue: No ]
    Urinalysis parameters included: urine protein (UP), urine glucose (UG), urine ketones (UK), urine occult blood (UOB), and pH. The dipstick test gives results in a semi-quantitative manner. UP was categorized as missing (MS), no result (NR), negative (Neg), Trace, 1+, 2+, 3+ and 4+. UG results were categorized as MS, NR, Neg, normal, 5, 15(1+), 30(2+), 60(3+), 110(4+)UK parameters were categorized as as MS, NR, Neg, Trace(5), Small(15), Moderate(40), Large(80), Large(160). UOB parameters were categorized as MS, NR, Neg, 1+, 2+, 3+, Non haemolysed trace, and haemolysed trace. PH results were categorized as MS. NR, normalresult, Neg, and range of pH (from 5-9in increments of 0.5). Data for indicated parameters was reported at Baseline (BL) and Week 7 (W7). The Baseline value was the measurement taken at Day 1.

  • 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 [ Time Frame: Baseline and Week 24 of Part 2/3 up to Study Week 31 ] [ Designated as safety issue: No ]
    Urinalysis parameters included: urine protein (UP), urine glucose (UG), urine ketones (UK), urine occult blood (UOB), and pH. The dipstick test gives results in a semi-quantitative manner. UP was categorized as missing (MS), no result (NR), negative (Neg), Trace, 1+, 2+, 3+ and 4+. UG results were categorized as MS, NR, Neg, normal, 5, 15(1+), 30(2+), 60(3+), 110(4+)UK parameters were categorized as as MS, NR, Neg, Trace(5), Small(15), Moderate(40), Large(80), Large(160). UOB parameters were categorized as MS, NR, Neg, 1+, 2+, 3+, Non haemolysed trace, and haemolysed trace. PH results were categorized as MS. NR, normalresult, Neg, and range of pH (from 5-9in increments of 0.5). Data for indicated parameters was reported at Baseline (BL) and Week 24 (W24). The Baseline value was the measurement taken at Day 1.

  • Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 1 [ Time Frame: From Treatment + 1 day up to Week 24 of Part1 ] [ Designated as safety issue: No ]
    An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment should be exercised in other situations.

  • Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2 [ Time Frame: From Treatment + 1 day up to Week 7 of Part 2 ] [ Designated as safety issue: No ]
    An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment should be exercised in other situations.

  • Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2/3 [ Time Frame: From Treatment + 1 day up to Week 31 of Part2/3 ] [ Designated as safety issue: No ]
    An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment should be exercised in other situations.

  • Number of Participants With a Change in Visual Acuity and a Change Due to Worsening of Cataracts During Part 1 [ Time Frame: Baseline, 3and 6-mo Follow-up of Part 1 ] [ Designated as safety issue: No ]
    The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. The number of participants with a change in visual acuity and worsening visual acuity due to cataracts since Baseline are presented for Part 1 Follow-up Visits at 3-months (FU3) and at 6-months (FU6). Change in visual acuity since Baseline is displayed under the left eye but applies to both eyes. Change in visual acuity (VA) is categorized as "yes" or "no". Change due to cataracts is categorized as "yes" or "no".

  • Number of Participants With a Change in Visual Acuity and a Change Due to Worsening of Cataracts [ Time Frame: BL, 3 and 6mo Follow-up of Part 2/3 ] [ Designated as safety issue: No ]
    The visual acuity assessment was performed by an ophthalmologist or an optometrist under the guidance of an ophthalmologist. Visual acuity is defined as acuteness or clearness of vision. Number of participants with a change in visual acuity and change in visual acuity due to the worsening of cataracts since Baseline are presented for Part 2/3 Follow-up Visits at 3-months (FU3) and 6-months (FU6). Change in visual acuity since Baseline is displayed under the left eye but applies to both eyes. Change in visual acuity (VA) is categorized as "yes" or "no". Change due to cataracts is categorized as "yes" or "no".


Enrollment: 82
Study Start Date: September 2009
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: eltrombopag plus standard of care
eltrombopag
Drug: eltrombopag
thrombopoietin receptor agonist
Placebo Comparator: placebo plus standard of care
placebo
Drug: Placebo
placebo for comparison

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects between 1 year and <18 years of age at Day 1.
  • Written informed consent from subject's guardian and accompanying informed assent from subject (for children over 6 years old).
  • Confirmed diagnosis of chronic ITP, according to the American Society of Hematology / British Committee for Standards in Haematology (ASH/BCSH) guidelines [George, 1996; BCSH, 2003]. In addition, a peripheral blood smear or bone marrow examination should support the diagnosis of ITP with no evidence of other causes of thrombocytopenia.
  • Subjects who are refractory or have relapsed after at least one prior ITP therapy or are not eligible, for a medical reason, for other treatments.
  • Day 1 (or within 48 hours prior) platelet count <30 Gi/L.
  • Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have been completed at least 2 weeks prior to Day 1 or have been clearly ineffective.
  • Subjects treated with concomitant ITP medication (e.g. corticosteroids or azathioprine) must be receiving a dose that has been stable for at least 4 weeks prior to Day 1.
  • Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been completed at least 4 weeks prior to Day 1 or have clearly been ineffective.
  • Subjects must have prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) within 80 to 120% of the normal range.
  • Subjects must have a complete blood count (CBC) not suggestive of another hematological disorder.
  • The following clinical chemistries for the subjects MUST NOT exceed the upper limit of normal (ULN) reference range by more than 20%: creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and alkaline phosphatase. In addition, total albumin must not be below the lower limit of normal (LLN) by more than 10%.
  • For subjects of child-bearing potential (after menarche): subject must not be sexually active or is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must use one of the following highly effective methods of contraception (i.e., Pearl Index <1.0%) from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:
  • Complete abstinence from intercourse;
  • Intrauterine device (IUD);
  • Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide);
  • Systemic contraceptives (combined or progesterone only).

Exclusion Criteria:

  • Any clinically relevant abnormality, other than ITP, identified on the screening examination or any other medical condition or circumstance, which in the opinion of the investigator makes the subject unsuitable for participation in the study or suggests another primary diagnosis (e.g. thrombocytopenia is secondary to another disease).
  • Concurrent or past malignant disease, including myeloproliferative disorder.
  • Subjects who are not suitable for continuation of their current therapy for at least 7 additional additional weeks.
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding Day 1.
  • History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
  • Diagnosis of secondary immune thrombocytopenia, including those with laboratory or clinical evidence of HIV infection, anti-phospholipid antibody syndrome, chronic hepatitis B infection, hepatitis C virus infection, or any evidence of active hepatitis at the time of subject screening.
  • Subject with Evans syndrome (autoimmune thrombocytopenia and autoimmune hemolysis).
  • Subjects with known inherited thrombocytopenia (e.g. MYH-9 disorders)
  • Subjects treated with drugs that affect platelet function (including but not limited to aspirin, clopidogrel and/or NSAIDs) or anti-coagulants for >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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00908037

  Show 33 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00908037     History of Changes
Other Study ID Numbers: 108062
Study First Received: May 21, 2009
Results First Received: September 29, 2014
Last Updated: October 30, 2014
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
France: Agence Française de Sécurité Sanitaire des Produits de Santé
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
thrombocytopenia
idiopathic thrombocytopenic purpura
ITP
pharmacokinetics
chronic ITP
pharmacodynamics
eltrombopag
pediatrics

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Thrombocytopenia
Autoimmune Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hematologic Diseases
Hemorrhage
Hemorrhagic Disorders
Immune System Diseases
Pathologic Processes
Signs and Symptoms
Skin Manifestations
Thrombotic Microangiopathies

ClinicalTrials.gov processed this record on November 25, 2014