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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00908037
First received: May 21, 2009
Last updated: February 6, 2014
Last verified: January 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: Crossover 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:
  • Proportion of subjects achieving platelet counts >=50 Gi/L at least once. [ Time Frame: Between days 8 and 43 of the randomized period of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects with platelet counts >=50 Gi/L during treatment in >=60% of assessments [ Time Frame: Between days 15 and 43 of the randomized treatment period. ] [ Designated as safety issue: No ]
  • Weighted mean platelet change (area under the platelet-time curve divided by duration). [ Time Frame: From baseline to Day 43 of the randomized period. ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving platelet counts>=50 Gi/L at any time. [ Time Frame: During the 24 weeks of eltrombopag dosing ] [ Designated as safety issue: No ]
  • Plasma concentrations of eltrombopag [ Time Frame: During the 24 weeks of eltrombopag treatment. ] [ Designated as safety issue: No ]
  • Maximum period of time subjects achieved a platelet count continuously >=50 Gi/L. [ Time Frame: During the 24 weeks of eltromobpag treatment. ] [ Designated as safety issue: No ]
  • Safety and tolerability parameters including blood pressure, respiratory and heart rate, ocular examinations, clinical laboratory assessments and frequency of all AE. [ Time Frame: During all on-therapy periods and 4 weeks post-therapy. Ocular examinations will include 12 and 24 weeks after completion of therapy. ] [ Designated as safety issue: No ]
  • Reduction or discontinuation of concomitant ITP medications [ Time Frame: During the 24 weeks of eltrombopag treatment. ] [ Designated as safety issue: No ]
  • Use of rescue treatment [ Time Frame: During the 24 weeks of eltrombopag treatment. ]
  • Quality of Life Measures using the Kids' ITP Tools (KIT) questionnaire. [ Time Frame: During all on-therapy periods. ]
  • Reduction of bleeding symptoms associated with ITP based on the WHO Bleeding Scale [ Time Frame: During all on-therapy periods and 4-week follow-up period. ]

Estimated Enrollment: 70
Study Start Date: September 2009
Estimated Study Completion Date: April 2014
Estimated 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
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
Last Updated: February 6, 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:
idiopathic thrombocytopenic purpura
thrombocytopenia
pharmacodynamics
ITP
eltrombopag
pharmacokinetics
chronic ITP
pediatrics

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

ClinicalTrials.gov processed this record on April 17, 2014