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 - EXTEND

• Register: EUCTR
• Last refreshed on: 7 December 2015
• Main ID: EUCTR2006-000471-14-FI
• Date of registration: 08/10/2007
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research and Development Limited
• Public 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 - EXTEND
• Scientific 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 - EXTEND
• Date of first enrolment: 30/11/2007
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000471-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Dose-adjustment If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria, Czech Republic, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Netherlands, Slovenia, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject has signed and dated a written informed consent.
2. Adults (=18 years) diagnosed with ITP according to the American Society for Hematology/British Committee for Standards in Haematology (ASH/BCSH) guidelines. In addition, the 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.
3. Prior completion of treatment and follow up periods in an ITP study of eltrombopag (e.g., TRA100773 or TRA102537/RAISE or TRA108057/REPEAT).
4. Subjects previously enrolled in Study TRA100773 must have completed the prescribed follow-up ophthalmic assessment at 6 months.
5. 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.
6. 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.
7. Subject has no intercurrent medical event, including thrombosis.
8. Subjects must have either initially responded (platelet count > 100,000/µL) 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.
9. 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 the first dose of study medication, or clearly be ineffective.
10. 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 the first dose of study medication. 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.
11. 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.
12. 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/microL (1.5 x 109/L) is required for inclusion (elevated WBC/ANC due to steroid treatment is acceptable).
13. 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%.
14. Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subject
Exclusion criteria:
1. 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).
2. Concurrent malignant disease and/or history of cancer treatment with cytotoxic chemotherapy and/or radiotherapy.
3. 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.
4. 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. artrial fibrillation), or subjects with a QTc >450 msec.
5. Female subjects who are nursing or pregnant (positive serum or urine beta-human chorionic gonadotrophin (beta-hCG) pregnancy test) at screening or pre-dose on Day 1.
6. History of alcohol/drug abuse.
7. Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
8. 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.
9. History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
10. 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.
11. A subject is planning to have cataract surgery.
12. In France, a subject is neither affiliated with nor a beneficiary of a social security category.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Immune thrombocytopenic purpura (ITP)
MedDRA version: 8.1 Level: LLT Classification code 10021245 Term: Idiopathic thrombocytopenic purpura

Intervention(s)

Product Name: Eltrombopag
Product Code: SB497115
Pharmaceutical Form: Tablet
INN or Proposed INN: eltrombopag
CAS Number: CASRN496775
Current Sponsor code: SB-497115
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 25-

Product Name: Eltrombopag
Product Code: SB497115
Pharmaceutical Form: Tablet
INN or Proposed INN: eltrombopag
CAS Number: CASRN496775
Current Sponsor code: SB-497115
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): Safety and tolerability parameters including, clinical laboratory tests, ocular examinations, and frequency of all adverse events

Secondary Objective: •Describe the clinical efficacy, PD, and durability of response when administered to previously treated subjects.
•Describe the effect of re-treatment on platelet counts in subjects previously treated with eltrombopag.
•Gain information on the optimal dosing of eltrombopag
•Describe the effect of eltrombopag on reduction and/or sparing of concomitant ITP therapies.
•Assess the impact of eltrombopag on physical and mental health status, the symptoms of fatigue and bleeding and bruising, and the impact of such symptoms on health-related quality of life.
Exploratory objectives are to assess effect of administration on anti-platelet antibody titers; to use proteomic analysis to identify proteins that correlate with safety and tolerability and/or predict response; the relationship between genetic variants and the PK, PD, safety and/or tolerability, or efficacy may be assessed.

Main Objective: To describe the long-term safety and tolerability of oral eltrombopag treatment of subjects with ITP with or without concomitant ITP medication.

Secondary ID(s)

TRA105325

2006-000471-14-SI