EXTEND (Eltrombopag Extended Dosing Study)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00351468
First received: July 10, 2006
Last updated: February 14, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Purpura, Thrombocytopenic, Idiopathic
Drug: eltrombopag olamine (SB-497115-GR)
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety and tolerability parameters including, clinical laboratory tests, ocular examinations, bone marrow biopsy, and frequency of all adverse events. [ Time Frame: For at least 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • To describe the effect of eltrombopag on reduction and/or sparing of concomitant ITP therapies, while maintaining a platelet count ≥ 50,000/mL. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving stable platelet counts ≥ 50,000/µL while remaining free of concomitant ITP medication during treatment with eltrombopag. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • Incidence and severity of signs and symptoms associated with ITP measured using the World Health Organization (WHO) bleeding scale and the ITP Bleeding Score. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • 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: [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • Medical Outcomes Trust Short Form 36 (SF-36v2 Acute Recall), the short form of the Motivation and Energy Scale (MEI-SF), [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • the stand-alone symptom sub-scale FACIT-Fatigue, and relevant bleeding and bruising questions from the FACT-thrombocytopenia subscale. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 302
Study Start Date: May 2006
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eltrombopag
Open-label eltrombopag
Drug: eltrombopag olamine (SB-497115-GR)
Eltrombopag at a dose up to 75mg daily
Other Name: eltrombopag olamine (SB-497115-GR)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00351468

  Show 112 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00351468     History of Changes
Other Study ID Numbers: TRA105325
Study First Received: July 10, 2006
Last Updated: February 14, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
eltrombopag olamine
SB-497115-GR
idiopathic thrombocytopenic purpura
thrombocytopenia
ITP
platelets

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

ClinicalTrials.gov processed this record on April 17, 2014