EXTEND (Eltrombopag Extended Dosing Study)

Condition(s) targeted: Idiopathic Thrombocytopenic Purpura; Purpura, Thrombocytopenic, Idiopathic

Intervention: eltrombopag olamine (SB-497115-GR) (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

Overall contact:
US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com

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.

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.

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Safety and tolerability parameters including, clinical laboratory tests, ocular examinations, and frequency of all adverse events.

Secondary outcome:

Frequency and severity of all AEs and SAEsClinical laboratory valuesVisual acuity measurements, assessments of lens opacities, measures of ocular health and cataract risk factors

•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.

•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.

•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.

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

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

•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).

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

•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:

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

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

US GSK Clinical Trials Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com

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GSK Investigational Site, Shanghai 200025, China; Active, not recruiting

GSK Investigational Site, Tianjin 300020, China; Completed

GSK Investigational Site, Brno 625 00, Czech Republic; Active, not recruiting

GSK Investigational Site, Olomouc 775 20, Czech Republic; Active, not recruiting

GSK Investigational Site, Praha 2 128 20, Czech Republic; Completed

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GSK Investigational Site, Kuopio 70210, Finland; Completed

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GSK Investigational Site, Créteil 94010, France; Active, not recruiting

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GSK Investigational Site, Seoul 136-705, Korea, Republic of; Active, not recruiting

GSK Investigational Site, Amersfoort 3816 CP, Netherlands; Completed

GSK Investigational Site, Amsterdam 1105 AZ, Netherlands; Completed

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GSK Investigational Site, Christchurch 8011, New Zealand; Completed

GSK Investigational Site, Grafton 1001, New Zealand; Completed

GSK Investigational Site, Takapuna, Auckland 0622, New Zealand; Active, not recruiting

GSK Investigational Site, Karachi 75300, Pakistan; Completed

GSK Investigational Site, Lahore 54600, Pakistan; Active, not recruiting

GSK Investigational Site, Lima Lima 27, Peru; Active, not recruiting

GSK Investigational Site, Bialystok 15-276, Poland; Active, not recruiting

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GSK Investigational Site, Bucharest 022328, Romania; Active, not recruiting

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GSK Investigational Site, Moscow 125167, Russian Federation; Active, not recruiting

GSK Investigational Site, Moscow 105 229, Russian Federation; Completed

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GSK Investigational Site, Novosibirsk 630087, Russian Federation; Not yet recruiting
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EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, St Petersburg 193024, Russian Federation; Not yet recruiting
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EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Kosice 041 90, Slovakia; Active, not recruiting

GSK Investigational Site, Presov 080 01, Slovakia; Active, not recruiting

GSK Investigational Site, Badalona 08916, Spain; Completed

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GSK Investigational Site, Madrid 28007, Spain; Completed

GSK Investigational Site, Madrid 28006, Spain; Completed

GSK Investigational Site, Palma de Mallorca 07014, Spain; Completed

GSK Investigational Site, Pamplona 31008, Spain; Completed

GSK Investigational Site, Santiago de Compostela 15706, Spain; Completed

GSK Investigational Site, Göteborg SE-413 45, Sweden; Completed

GSK Investigational Site, Stockholm SE-141 86, Sweden; Completed

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GSK Investigational Site, Taipei 100, Taiwan; Active, not recruiting

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EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

GSK Investigational Site, Tunis 1008, Tunisia; Recruiting
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EU GSK Clinical Trials Call Center, Phone: +44 (0) 20 8990 4466, Email: GSKClinicalSupportHD@gsk.com

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GSK Investigational Site, Reading RG1 5AN, United Kingdom; Completed

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GSK Investigational Site, Huntsville, Alabama 35805, United States; Completed

GSK Investigational Site, Mobile, Alabama 36608, United States; Completed

GSK Investigational Site, Jonesboro, Arkansas 72401, United States; Completed

GSK Investigational Site, Muenchen, Bayern 80639, Germany; Completed

GSK Investigational Site, Duarte, California 91010, United States; Completed

GSK Investigational Site, Los Angeles, California 90033, United States; Completed

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GSK Investigational Site, Bologna, Emilia-Romagna 40138, Italy; Active, not recruiting

GSK Investigational Site, Miami, Florida 33136, United States; Completed

GSK Investigational Site, Atlanta, Georgia 30341, United States; Completed

GSK Investigational Site, Savannah, Georgia 31405, United States; Completed

GSK Investigational Site, Giessen, Hessen 35392, Germany; Completed

GSK Investigational Site, Peoria, Illinois 61614, United States; Completed

GSK Investigational Site, Albano Laziale (Roma), Lazio 00041, Italy; Active, not recruiting

GSK Investigational Site, Milano, Lombardia 20132, Italy; Completed

GSK Investigational Site, New Orleans, Louisiana 70115, United States; Completed

GSK Investigational Site, Boston, Massachusetts 02114, United States; Completed

GSK Investigational Site, Detroit, Michigan 48202, United States; Completed

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GSK Investigational Site, Albuquerque, New Mexico 87109, United States; Completed

GSK Investigational Site, Kogarah, New South Wales 2217, Australia; Active, not recruiting

GSK Investigational Site, New York, New York 10021, United States; Active, not recruiting

GSK Investigational Site, Hannover, Niedersachsen 30159, Germany; Completed

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GSK Investigational Site, Cleveland, Ohio 44106, United States; Completed

GSK Investigational Site, Hamilton, Ontario L8S 4K1, Canada; Active, not recruiting

GSK Investigational Site, Portland, Oregon 97227, United States; Completed

GSK Investigational Site, Montreal, Quebec H3T 1E2, Canada; Active, not recruiting

GSK Investigational Site, Montreal, Quebec H2L 4M1, Canada; Active, not recruiting

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Starting date: June 2006
Last updated: October 13, 2011