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

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.

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.

Study Overview

• Status: Completed
• Conditions: Purpura, Thrombocytopaenic, Idiopathic
• Intervention / Treatment: Drug: eltrombopag; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • GSK Investigational Site
• France
  • Bordeaux cedex, France, 33076
    • GSK Investigational Site
  • Paris Cedex 19, France, 75935
    • GSK Investigational Site
  • Paris cedex 12, France, 75571
    • GSK Investigational Site
• Netherlands
  • Rotterdam, Netherlands, 3015 GJ
    • GSK Investigational Site
• Spain
  • Barakaldo (Vizcaya), Spain, 48903
    • GSK Investigational Site
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Madrid, Spain, 28009
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • GSK Investigational Site
  • London, United Kingdom, W2 1NY
    • GSK Investigational Site
  • Manchester, United Kingdom, M13 9WL
    • GSK Investigational Site
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • GSK Investigational Site
  • Southampton, United Kingdom, SO16 6YD
    • GSK Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • GSK Investigational Site
  • California
    • Orange, California, United States, 92868
      • GSK Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32207
      • GSK Investigational Site
    • Orlando, Florida, United States, 32806
      • GSK Investigational Site
    • Orlando, Florida, United States, 32827
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611-2605
      • GSK Investigational Site
    • Peoria, Illinois, United States, 61614
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • GSK Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10021
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • GSK Investigational Site
    • Durham, North Carolina, United States, 27710
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • GSK Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15224
      • GSK Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • GSK Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • GSK Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	From Day 8 up to Day 43 of Part 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Between Day 15 and Day 43 of Part 2
Weighted Mean Platelet Count	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.	Baseline and Day 43 of Part 2
Percentage of Participants Achieving Platelet Counts >=50Gi/L at Any Time During the 24 Weeks of Eltrombopag Dosing During Part 1.	The percentage of participants achieving platelet counts >=50Gi/L at least once at any time during the 24 weeks of eltrombopag treatment were reported.	From Day 1 of treatment up to Week 24 of Part 1
Percentage of Participants Achieving Platelet Counts >=50 Gi/L at Any Time During the 31 Weeks of Eltrombopag Treatment During Part 2/ 3.	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.	Part 2/3 up to Study Week 31
Population Pharmacokinetic (PK) Assessment for Eltrombopag for AUC(0-t) During Part 1, 2, and 2/3.	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.	From Day 1 of treatment up to Study Week 31
Population Pharmacokinetic (PK) Assessments for Eltrombopag for Cmax and Ct During Part 1, 2, and 2/3.	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.	From Day 1 of treatment up to Study Week 31
Population Pharmacokinetic (PK) Assessments for Eltrombopag for Tmax During Part 1, 2, and 2/3	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.	From Day 1 of treatment up to Study Week 31
Population Pharmacokinetic (PK) Assessments for Eltrombopag for CL/F During Part 1, 2, and 2/3	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.	From Day 1 of treatment up to Study Week 31
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	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	From Baseline through Week 7 of Part 2
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	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.	From Baseline 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.	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.	From Baseline up to Week 24+ 1 day of Part 1
Percentage of Participants Who Reduced or Discontinued Baseline Concomitant ITP Medications During the 24 Weeks of Eltrombopag Treatment During Part 2/ 3	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.	From Baseline to the end of treatment up to Week 31 + 1 day of Part 2/3
Number of Participants Who Required a Protocol-defined Rescue Treatment During Part 2/3	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.	From Baseline to the end of treatment up to Week 31 + 1 day of Part2/3
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	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.	Baseline, Week 6, Week 12, and Week 24 of Part 1
Kids' ITP Tool (KIT) Questionnaire Total Score at Baseline and Week 6as Assessed Using the KIT Questionnaire During the Randomized Period, Part 2	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.	Baseline and Week 6 of Part 2
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	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.	From Baseline to end of treatment up to Study Week 31
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	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.	From Baseline through Week 7 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	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.	From Baseline of Part 2/3 through Follow-up
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	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	Post-Baseline from Week 1 through Follow-up up to Study Week 35
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	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	Post-Baseline from Week 1 through Follow-up up to Study Week 35
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	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	Post-Baseline from Week 1 through Follow-up up to Study Week 35
Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 1	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.	From Baseline up to Study Week 24 of Part 1
Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2	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.	From Baseline and post-Baseline up to Study Week 7 of Part 2
Number of Participants With a Positive Urine Microscopy Parameters Any Time Post-Baseline During Part 2/3	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.	From Baseline and post-Baseline up to Study Week 31 of Part 2/3
Number of Participants With the Indicated Vital Signs Falling Outside of the Reference Range During Part 1, Part 2, and Part 2/3	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.	From Baseline through Study Week 35
Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Dose-Finding Period, Part 1	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.	From Baseline through Week 24
Mean Respiratory Rate at Baseline and the Maximum Post-Baseline Value Recorded During the Randomized Period, Part 2	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.	From Week 1 to Week 7 of Part 2
Mean Respiratory Rate at Baseline and Maximum Post-Baseline Visit During Part 2/3	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.	From Week 1 to Follow-up Week 4 of Part 2/3 up to Study Week 35
Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Dose-Finding Period, Part 1	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..	From Week 1 to Follow-up Week 4 of Part 1, up to Study Week 28
Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Randomized Period, Part 2	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.	From Week 1 to Week 7 of Part 2
Mean Pulse Rate at Baseline and the Maximum Post-Baseline Visit Recorded During the Eltrombopag Only Period Part 2/3	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.	From Week 1to Follow-up Week 4 of Part 2/3, up to Study Week 35
Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 24 During the Dose-Finding Period, Part 1	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.	Baseline and Week 24 of Part 1
Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 7 During the Randomized Period,Part 2	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.	Baseline and Week 7 of Part 2
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	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.	Baseline and Week 24 of Part 2/3 up to Study Week 31
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 1	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.	From Treatment + 1 day up to Week 24 of Part1
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2	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.	From Treatment + 1 day up to Week 7 of Part 2
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During Part 2/3	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.	From Treatment + 1 day up to Week 31 of Part2/3
Number of Participants With a Change in Visual Acuity and a Change Due to Worsening of Cataracts During Part 1	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".	Baseline, 3and 6-mo Follow-up of Part 1
Number of Participants With a Change in Visual Acuity and a Change Due to Worsening of Cataracts	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".	BL, 3 and 6mo Follow-up of Part 2/3

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Wire MB, Li X, Zhang J, Sallas W, Aslanis V, Ouatas T. Modeling and Simulation Support Eltrombopag Dosing in Pediatric Patients With Immune Thrombocytopenia. Clin Pharmacol Ther. 2018 Dec;104(6):1199-1207. doi: 10.1002/cpt.1066. Epub 2018 Apr 17.
• Grainger JD, Blanchette VS, Grotzinger KM, Roy A, Bussel JB. Health-related quality of life in children with chronic immune thrombocytopenia treated with eltrombopag in the PETIT study. Br J Haematol. 2019 Apr;185(1):102-106. doi: 10.1111/bjh.15732. Epub 2018 Dec 27.
• Bussel JB, de Miguel PG, Despotovic JM, Grainger JD, Sevilla J, Blanchette VS, Krishnamurti L, Connor P, David M, Boayue KB, Matthews DC, Lambert MP, Marcello LM, Iyengar M, Chan GW, Chagin KD, Theodore D, Bailey CK, Bakshi KK. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol. 2015 Aug;2(8):e315-25. doi: 10.1016/S2352-3026(15)00114-3. Epub 2015 Jul 28. Erratum In: Lancet Haematol. 2015 Oct;2(10):e407.

Study record dates

Study Major Dates

• Study Start: September 30, 2009
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: May 21, 2009
• First Submitted That Met QC Criteria: May 21, 2009
• First Posted (Estimate): May 25, 2009

Study Record Updates

• Last Update Posted (Actual): October 12, 2018
• Last Update Submitted That Met QC Criteria: September 13, 2018
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: pediatrics; pharmacokinetics; pharmacodynamics; eltrombopag; thrombocytopenia; ITP; chronic ITP; idiopathic thrombocytopenic purpura
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: 108062