Last updated: 11/04/2018 12:56:45
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.

EXTEND (Eltrombopag Extended Dosing Study)EXTEND

GSK study ID
TRA105325
Clinicaltrials.gov ID
NCT00351468
EudraCT ID
2006-000471-14
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: EXTEND (Eltrombopag Extended Dosing Study): An extension study of eltrombopag olamine (SB-497115-GR) in adults, with idiopathic thrombocytopenic purpura (ITP), previously enrolled in an eltrombopag study.
Trial description: An open-label, dose-adjustment, extension study to evaluate the safety and efficacy of eltrombopag for the treatment of subjects with idiopathic thrombocytopenic purpura (ITP) who have previously been enrolled in an eltrombopag trial. This study will allow adjustment of the eltrombopag dose to achieve an individualized dose and schedule for each subject. In addition, the ability to reduce the dose of concomitant ITP medications in the presence of eltrombopag, while maintaining platelet counts = 50,000/microL will be investigated.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Safety and tolerability parameters including, clinical laboratory tests, ocular examinations, bone marrow biopsy, and frequency of all adverse events.

Timeframe: For at least 2 years

Secondary outcomes:

Proportion of subjects achieving stable platelet counts ≥ 50,000/µL while remaining free of concomitant ITP medication during treatment with eltrombopag.

Timeframe: For at least 2 years

Proportion of subjects needing rescue treatment (Rescue treatment is defined as a composite of: new ITP medication, increased dose of a concomitant ITP medication, platelet transfusion, and splenectomy).

Timeframe: For at least 2 years

Proportion of subjects who responded to eltrombopag in a previous study and who respond to retreatment with a rise in platelet count to either ≥ 50,000/µL or ≥30,000/µL will be evaluated.

Timeframe: For at least 2 years

the stand-alone symptom sub-scale FACIT-Fatigue, and relevant bleeding and bruising questions from the FACT-thrombocytopenia subscale.

Timeframe: For at least 2 years

Proportion of subjects achieving a platelet count ≥ 50,000/µL during treatment with eltrombopag. The proportion of subjects achieving a platelet count ≥ 30,000/µL will also be evaluated.

Timeframe: For at least 2 years

Quality of life and severity associated with fatigue, motivation and energy, bleeding and bruising, and physical and mental health status using the following tools and assessments:

Timeframe: For at least 2 years

Incidence and severity of signs and symptoms associated with ITP measured using the World Health Organization (WHO) bleeding scale and the ITP Bleeding Score.

Timeframe: For at least 2 years

Medical Outcomes Trust Short Form 36 (SF-36v2 Acute Recall), the short form of the Motivation and Energy Scale (MEI-SF),

Timeframe: For at least 2 years

To describe the effect of eltrombopag on reduction and/or sparing of concomitant ITP therapies, while maintaining a platelet count ≥ 50,000/mL.

Timeframe: For at least 2 years

Maximum duration of platelet count elevation ≥ 50,000/µL during treatment with eltrombopag. The maximum duration of platelet count elevation ≥ 30,000/µL will also be evaluated.

Timeframe: For at least 2 years

Interventions:
  • Drug: eltrombopag olamine (SB-497115-GR)
    • Enrollment:
    302
    Primary completion date:
    Not applicable
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Purpura, Thrombocytopaenic, Idiopathic
    Product
    eltrombopag
    Collaborators
    Not applicable
    Study date(s)
    June 2006 to July 2015
    Type
    Interventional
    Phase
    3

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    none
    • Subjects are eligible for participation in this study if they were previously randomized to an ITP study of eltrombopag (e.g., TRA100773 or TRA102537/RAISE or TRA108057/REPEAT) and meet the below inclusion and exclusion criteria.
    • Inclusion Criteria:
    • A subject will not be eligible for inclusion in this study if any of the following criteria apply:
    • 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 another primary diagnosis (e.g., thrombocytopenia is secondary to another disease).
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Subjects are eligible for participation in this study if they were previously randomized to an ITP study of eltrombopag (e.g., TRA100773 or TRA102537/RAISE or TRA108057/REPEAT) and meet the below inclusion and exclusion criteria. Inclusion Criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply:
    • Subject has signed and dated a written informed consent.
    • Adults (≥18 years) diagnosed with ITP according to the American Society for Hematology/British Committee for Standards in Haematology (ASH/BCSH) guidelines [George, 1996; BCSH, 2003]. In addition, a peripheral blood smear should support the diagnosis of ITP with no evidence of other disease causative of thrombocytopenia (e.g., pseudo thrombocytopenia, myelofibrosis). The physical examination should not suggest any disease which may cause thrombocytopenia other than ITP.
    • Prior completion of treatment and follow up periods in an ITP study of eltrombopag (e.g., TRA100773 or TRA102537/RAISE or TRA108057/REPEAT).
    • Subjects previously enrolled in Study TRA100773 must have completed the prescribed follow-up ophthalmic assessment at 6 months.
    • Subjects previously enrolled in TRA102537/RAISE or other studies that may lead into EXTEND (e.g., TRA108057/REPEAT) must have completed the treatment and follow-up periods as defined in that protocol.
    • Subject experienced no eltrombopag-related toxicity or other drug intolerance on prior eltrombopag study (e.g., TRA100773 or TRA102537/RAISE or TRA108057/REPEAT) even if resolved; subjects discontinued from previous study due to toxicity will not be eligible unless they received placebo.
    • Subject has no intercurrent medical event, including thrombosis.
    • Subjects must have either initially responded (platelet count > 100,000/mL) to a previous ITP therapy or have had a bone marrow examination consistent with ITP within 3 years to rule out myelodysplastic syndromes or other causes of thrombocytopenia
    • Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have been completed at least 1 week prior to first dose of study medication and the platelet count must show a clear downward trend after the last treatment with immunoglobulins. Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been completed at least 4 weeks prior to randomization, or clearly be 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 randomization. Subjects treated with cyclosporine A, mycophenolate mofetil or danazol must be receiving a dose that has been stable for at least 3 months prior to the first dose of study medication.
    • Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must be within 80 to 120% of the normal range with no history of hypercoagulable state.
    • A complete blood count (CBC), within the reference range (including WBC differential not indicative of a disorder other than ITP), with the following exceptions:
    • Hemoglobin: Subjects with hemoglobin levels between 10.0 g/dL and the lower limit of normal are eligible for inclusion, if anemia is clearly attributable to ITP (excessive blood loss).
    • ANC≥1500/mL (1.5 x 10^9/L) is required for inclusion (elevated WBC/ANC due to steroid treatment is acceptable).
    • The following clinical chemistries MUST NOT exceed the upper limit of normal (ULN) reference range by more than 20%: creatinine, ALT, AST, total bilirubin, and alkaline phosphatase. In addition, total albumin must not be below the lower limit of normal (LLN) by more than 10%.
    • Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and 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);
    • Male partner is sterile prior to entry into the study and is the only partner of the female;
    • Systemic contraceptives (combined or progesterone only).
    • Subject is able to understand and comply with protocol requirements and instructions.
    Exclusion criteria:
    • A subject will not be eligible for inclusion in this study if any of the following criteria apply:
    • 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 another primary diagnosis (e.g., thrombocytopenia is secondary to another disease).
    • Concurrent malignant disease and/or history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy.
    • Any prior history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), AND≥two of the following risk factors: hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, ATIII deficiency, etc), or any other family history of arterial or venous thrombosis
    • Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association [NYHA] Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc >450 msec.
    • Female subjects who are nursing or pregnant (positive serum or urine b-human chorionic gonadotrophin (b-hCG) pregnancy test) at screening or pre-dose on Day 1.
    • History of alcohol/drug abuse.
    • Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
    • Subject 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 the study start and until the end of the study.
    • History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
    • All subjects with secondary immune thrombocytopenia, including those with laboratory or clinical evidence of HIV infection, antiphospholipid antibody syndrome, chronic hepatitis B infection, hepatitis C virus infection, or any evidence for active hepatitis at the time of subject screening. If a potential subject has no clinical history that would support HIV infection or hepatitis infection, no further laboratory screening is necessary; however, standard medical practice would suggest further evaluation of patients who have risk factors for these infections.
    • A subject is planning to have cataract surgery.
    • In France, a subject is neither affiliated with nor a beneficiary of a social security category. Other Eligibility Criteria Considerations: To assess any potential impact on subject eligibility with regard to safety, the investigator must refer to the following document(s) for detailed information regarding warnings, precautions, contraindications, adverse events, and other significant data pertaining to the investigational product(s) being used in this study: CIB, SPM.

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    No study documents available.

    Results overview

    Study Results yet to be posted

    Recruitment status
    No longer a GSK study
    Actual primary completion date
    Not applicable
    Actual study completion date
    2015-06-07

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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