Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body. (PETIT2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01520909
First received: December 21, 2011
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to investigate the efficacy, safety and tolerability of eltrombopag in children with previously treated chronic immune thrombocytopenia who are between 1 and 17 years of age. This is a 2 part study. In part 1, patients will be randomized to receive either eltrombopag or placebo for 13 weeks. All patients who complete part 1 will enter part 2. In part 2, all patients will receive 24 weeks of eltrombopag.


Condition Intervention Phase
Oedema
Drug: Eltrombopag
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Two Part, Double-blind, Randomized, Placebo-controlled and Open-label Study to Investigate the Efficacy, Safety and Tolerability of Eltrombopag, a Thrombopoietin Receptor Agonist, in Pediatric Patients With Previously Treated Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP). PETIT2: Eltrombopag in PEdiatric Patients With Thrombocytopenia From ITP

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • The proportion of patients who achieve platelet counts ≥50Gi/L [ Time Frame: Weeks 5-12 of Part 1 ] [ Designated as safety issue: No ]
    Percentage of patients who achieve a platelet count of greater or equal to 50 Gi/L in 6 out of last 8 weeks


Secondary Outcome Measures:
  • The odds of achieving platelet counts ≥ 50 Gi/L [ Time Frame: Weeks 1-12 of Part 1 ] [ Designated as safety issue: No ]
    Eltrombopag compared to placebo groups

  • Weighted mean platelet change (area under the platelet-time curve divided by duration) [ Time Frame: first 12 weeks in Part 1 ] [ Designated as safety issue: No ]
    Area under the platelet-time curve divided by the duration of treatment with study medication

  • The proportion of patients who achieve platelet counts ≥ 50 Gi/L at any time during the first 6 weeks of Part 1. [ Time Frame: first 6 weeks in Part 1 ] [ Designated as safety issue: No ]
    Percentage of patients of achieve a platelet count of greater or equal to 50 Gi/L

  • The proportion of patients who achieve platelet counts ≥ 50 Gi/L at any time during the first 12 weeks of Part 1. [ Time Frame: first 12 weeks in Part 1 ] [ Designated as safety issue: No ]
    Percentage of patients of achieve a platelet count of greater or equal to 50 Gi/L

  • The proportion of patients who achieve platelet counts ≥ 50 Gi/L at any time during Part 2. [ Time Frame: 24 weeks (Part 2) ] [ Designated as safety issue: No ]
    Percentage of patients of achieve a platelet count of greater or equal to 50 Gi/L

  • Maximum period of time with platelet counts continuously ≥ 50 Gi/L during the first 12 weeks of Part 1. [ Time Frame: first 12 weeks in Part 1 ] [ Designated as safety issue: No ]
    Number of weeks with platelet counts continuously greater than or equal to 50 Gi/L

  • The proportion of weeks in which platelet counts ≥ 50 Gi/L, between weeks 4-24 of Part 2. [ Time Frame: Weeks 4-24 of Part 2 ] [ Designated as safety issue: No ]
    Percentage of weeks with platelet counts greater than or equal to 50 Gi/L

  • Maximum period of time with platelet counts continuously ≥ 50 Gi/L during Part 2. [ Time Frame: 24 weeks (Part 2) ] [ Designated as safety issue: No ]
    Number of weeks with platelet counts continuously greater than or equal to 50 Gi/L

  • The proportion of patients who reduced or discontinued baseline concomitant ITP medications during Part 2. [ Time Frame: 24 weeks (Part 2) ] [ Designated as safety issue: No ]
    The percentage of patients who stopped or reduced dose of other ITP medications

  • The proportion of patients who required protocol-defined rescue treatment during Part 1. [ Time Frame: 13 weeks (Part 1) ] [ Designated as safety issue: No ]
    The percentage of patients who required rescue treatment for ITP

  • The proportion of patients who required protocol-defined rescue treatment during Part 2. [ Time Frame: 24 weeks (Part 2) ] [ Designated as safety issue: No ]
    The percentage of patients who required rescue treatment for ITP

  • Incidence and severity of symptoms associated with ITP, including bleeding, bruising and petechiae, measured using the World Health Organization (WHO) Bleeding Scale during Part 1. [ Time Frame: 13 weeks (Part 1) ] [ Designated as safety issue: No ]
    Change in score on the WHO bleeding scale

  • Incidence and severity of symptoms associated with ITP, including bleeding, bruising and petechiae, measured using the World Health Organization (WHO) Bleeding Scale during Part 2. [ Time Frame: 24 weeks (Part 2) ] [ Designated as safety issue: No ]
    Change in score on the WHO bleeding scale

  • Frequency of adverse events [ Time Frame: 61 weeks (Part 1, Part 2 and follow-up period) ] [ Designated as safety issue: No ]
    Proportion of patients reporting any adverse event

  • Clinical Laboratory Assessments (clinical chemistry tests, coagulation parameters, hematology tests, peripheral blood smear, and urinalysis tests) [ Time Frame: 37 weeks (Part 1 and Part 2) ] [ Designated as safety issue: No ]
    Change in clinical chemistry, coagulation, hematology, peripheral blood smear or urinalysis tests.

  • Ophthalmic Examination (visual acuity, intraocular pressure, lens opacity measured using the AREDS scale) [ Time Frame: 61 weeks (Part 1, Part 2 and follow-up period) ] [ Designated as safety issue: No ]
    Change in visual acuity, intraocular pressure, opacity of the lens (AREDS score).

  • Vital signs including Blood pressure (systolic/diastolic) and pulse [ Time Frame: 37 weeks (Part 1 and Part 2) ] [ Designated as safety issue: No ]
    Change in blood pressure (systolic and diastolic blood pressure values) or heart rate (pulse).

  • Apparent clearance following oral dosing (CL/F) of eltrombopag [ Time Frame: 37 weeks (Part 1 and Part 2) ] [ Designated as safety issue: No ]
    Population pharmacokinetic measure

  • Intercompartmental clearence (Q/F) of eltrombopag [ Time Frame: 37 weeks (Part 1 and Part 2) ] [ Designated as safety issue: No ]
    Population pharmacokinetic measure

  • Volume of central compartment (Vc/F) of eltrombopag [ Time Frame: 37 weeks (Part 1 and Part 2) ] [ Designated as safety issue: No ]
    Population pharmacokinetic measure

  • Volume of peripheral compartment (Vp/F) of eltrombopag [ Time Frame: 37 weeks (Part 1 and Part 2) ] [ Designated as safety issue: No ]
    Population pharmacokinetic measure

  • absorption rate constant (Ka) of eltrombopag [ Time Frame: 37 weeks (Part 1 and Part 2) ] [ Designated as safety issue: No ]
    Population pharmacokinetic measure


Enrollment: 92
Study Start Date: March 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eltrombopag plus standard of care
Part 1, double-blind treatment group
Drug: Eltrombopag
Thrombopoietin receptor agonist
Placebo Comparator: Placebo plus standard of care
Part 1, double-blind treatment group
Drug: Placebo
Placebo with no active pharmaceutical ingredient
Experimental: Eltrombopag plus standard of care (Part 2 open-label)
Part 2, open-label
Drug: Eltrombopag
Thrombopoietin receptor agonist

Detailed Description:

This is a two part, double-blind, randomized, placebo-controlled and open-label Phase III study to investigate the efficacy, safety and tolerability of eltrombopag in pediatric patients with previously treated chronic ITP. In Part 1, patients will be randomized to receive eltrombopag or placebo in a 13-week double-blind, placebo-controlled treatment period. After completing Part 1, patients will begin Part 2, in which they will receive eltrombopag in an open-label manner during a 24-week treatment period.

  Eligibility

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

Inclusion Criteria:

  • Written informed consent must be obtained from the patient's guardian and accompanying informed assent from the patient (for children over 6 years old)
  • Patients must be between 1 year and <18 years of age at Day 1
  • Patients will have a confirmed diagnosis of chronic ITP for at least 1 year, at screening, according to the guidelines published in the International Working Group Report
  • A peripheral blood smear or bone marrow examination will support the diagnosis of ITP with no evidence of other causes of thrombocytopenia.
  • Patients must be refractory or have relapsed after at least one prior ITP therapy, or patients must be unable, for a medical reason, to continue other ITP treatments.
  • Patients must have a 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 these therapies must have been completed at least 1 week prior to Day 1 and have been clearly ineffective.
  • Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been completed at least 4 weeks prior to Day 1.
  • Patients 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.
  • Patients must have a complete blood count (CBC) not suggestive of another hematological disorder.
  • Patients must have the following laboratory results:
  • prothrombin time international normalized ratio (INR) and activated partial thromboplastin time (aPTT) within 80 to 120% of the normal range.
  • clinical chemistries that do NOT exceed the upper limit of normal reference range by more than 20% for the following: creatinine, ALT, AST, total bilirubin, and alkaline phosphatase.
  • total albumin that is not below the lower limit of normal by more than 10%.
  • Female patients of child-bearing potential (after menarche) must:
  • have a negative pregnancy test within 24 hours of first dose of study treatment,
  • agree and be able to provide a blood or urine specimen for pregnancy testing during the study,
  • agree to use effective contraception during the study and for 28 days following the last dose of study treatment, and not be lactating.
  • Male patients with a female partner of childbearing potential must agree to use effective contraception from 2 weeks prior to administration of the first dose of study treatment until 3 months after the last dose of study treatment.
  • In France, a patient will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

  • Patients with 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 patient unsuitable for participation in the study or suggests another primary diagnosis (e.g. Thrombocytopenia is secondary to another disease).
  • Patients with concurrent or past malignant disease, including myeloproliferative disorder.
  • Patients expected not to be suitable for continuation of their current therapy for at least 13 additional weeks.
  • Patients with a history of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
  • Patients with a 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.
  • Patients with Evans syndrome (autoimmune thrombocytopenia and autoimmune hemolysis).
  • Patients with known inherited thrombocytopenia (e.g. MYH9 disorders).
  • Patients treated with any medication that affects 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.
  • Patients who have received treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding Day 1.
  • Patients who have previously received eltrombopag or any other thrombopoietin receptor agonist.
  • Any patient considered to be a child in care, defined as one who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. This can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a child in care does not include a child who is adopted or who has an appointed legal guardian.
  • Patients who have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipients that contraindicates their participation.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with the patient's safety or compliance to the study procedures.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01520909

  Show 51 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01520909     History of Changes
Other Study ID Numbers: 115450, 2011-002184-17
Study First Received: December 21, 2011
Last Updated: April 10, 2014
Health Authority: Spain: Agencia Espanola de Medicamentos y Productos Sanitarios
Poland: Ethics Committees
Thailand: Ethical Committee
Argentina: Ministry of Health - A.N.M.A.T
Russia: Ethics Committee
Argentina: Ethics Review Board
United Kingdom: Ethics Committee
Czech Republic: Ethics Committee
Italy: Ethics Committee
Hong Kong Ministry of Health
United States: Food and Drug Administration
Poland: Ministry of Health
Thailand: Ministry of Public Health
Taiwan: Food and Drug Administration, Department of Health
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Italy: A.I.F.A.: Agenzia Italiana del Farmaco (Italian Agency for Medicines)
Russia: Ministry of Health of the Russian Federation
Israel: Ministry of Health
Spain: Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Czech Republic: Statni ustav pro kontrolu leciv

Keywords provided by GlaxoSmithKline:
idiopathic thrombocytopenic purpura
eltrombopag
Chronic Immune Thrombocytopenia
thrombocytopenia
platelet disorder
immune thrombocytopenic purpura
chronic ITP
pediatrics

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

ClinicalTrials.gov processed this record on April 17, 2014