Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00351468




Registration number
NCT00351468
Ethics application status
Date submitted
10/07/2006
Date registered
12/07/2006
Date last updated
17/04/2017

Titles & IDs
Public title
EXTEND (Eltrombopag Extended Dosing Study)
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.
Secondary ID [1] 0 0
TRA105325
Universal Trial Number (UTN)
Trial acronym
EXTEND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Purpura, Thrombocytopaenic, Idiopathic 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - eltrombopag olamine (SB-497115-GR)

Experimental: Eltrombopag - Open-label eltrombopag


Treatment: Drugs: eltrombopag olamine (SB-497115-GR)
Eltrombopag with starting dose of 50mg daily, max dose of 75mg daily and min dose of 25mg daily or less frequently. Modifications were given to maintain platelet count in range of 50 to 200 Gi/L.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Summary of On-Therapy Adverse Events (Safety Population)
Timepoint [1] 0 0
Start date was the first dose of investigational product and up to the day after the last dose . Post-therapy: start date was more than 1 day after the last dose and up to 30 days after last dose of investigational product up to week 364
Secondary outcome [1] 0 0
Subjects Achieving Maximum Platelet Counts Greater Than or Equal to 30 Gi/L or 50 Gi/L in the Absence of Rescue Medication
Timepoint [1] 0 0
Baseline up to 2 years
Secondary outcome [2] 0 0
Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication
Timepoint [2] 0 0
Baseline up to Year 7/Week 364
Secondary outcome [3] 0 0
Number 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
Timepoint [3] 0 0
Baseline up to 2 years
Secondary outcome [4] 0 0
Number of Participants With Reduction and/or Sparing of Concomitant ITP Therapies, While Maintaining a Platelet Count = 50,000/mL.
Timepoint [4] 0 0
Baseline up to 2 years
Secondary outcome [5] 0 0
Number of Subjects Who Required Rescue Therapy During Treatment With Eltrombopag.
Timepoint [5] 0 0
Baseline up to 2 years
Secondary outcome [6] 0 0
Maximum ITP Bleeding Score at Any Time During the Study During All Stages.
Timepoint [6] 0 0
Baseline up to 2 years
Secondary outcome [7] 0 0
Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline
Timepoint [7] 0 0
Baseline, beginning of each stage, change in therapy and minimum frequency of every 3 months during stages, prior to early discontinuation, up to 2 years
Secondary outcome [8] 0 0
Best Post-Baseline Change in the Short Form of the Motivation and Energy Scale (MEI-SF) From Any Time Point Compared With Baseline
Timepoint [8] 0 0
Baseline, beginning of each stage, change in therapy and minimum frequency of every 3 months during stages, prior to early discontinuation, up to 2 years
Secondary outcome [9] 0 0
Best Post-Baseline Change in the FACIT-Fatigue 13 Item Subscale Score From Any Time Point Compared to Baseline
Timepoint [9] 0 0
Baseline, beginning of each stage, change in therapy and minimum frequency of every 3 months during stages, prior to early discontinuation, up to 2 years
Secondary outcome [10] 0 0
Best Post-Baseline Change in the FACT-TH6 at Any Time Point Compared to Baseline
Timepoint [10] 0 0
Baseline, beginning of each stage, change in therapy and minimum frequency of every 3 months during stages, prior to early discontinuation, up to 2 years

Eligibility
Key inclusion criteria
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 diagnosis.
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2015
Sample size
Target
Accrual to date
Final
302
Recruitment in Australia
Recruitment state(s)
ACT,NSW
Recruitment hospital [1] 0 0
Novartis investigative Site - Garran
Recruitment hospital [2] 0 0
Novartis Investigative Site - Kogarah
Recruitment postcode(s) [1] 0 0
2606 - Garran
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Louisiana
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United States of America
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Massachusetts
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United States of America
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Michigan
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Minnesota
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United States of America
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New Mexico
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United States of America
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New York
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Ohio
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Oregon
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Texas
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United States of America
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Virginia
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Washington
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Austria
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Vienna
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Ontario
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Quebec
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China
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Jiang Su Province
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China
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Shanghai
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China
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Tianjin
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Czech Republic
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Brno
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Czech Republic
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Olomouc
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Odense
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Kuopio
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France
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France
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Pessac
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Bayern
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Germany
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Hessen
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Germany
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Hong Kong
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Kosice
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Presov
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Ljubljana
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Badalona/Barcelona
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Barcelona
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Madrid
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Palma de Mallorca
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Pamplona
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Sweden
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Göteborg
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Stockholm
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Taiwan
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Taipei
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Thailand
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Bangkok
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Thailand
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Khon Kaen
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Tunisia
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Montfleury
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Sfax
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Tunisia
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Sousse
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Tunis
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Ukraine
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Dnipropetrovsk
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Ukraine
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Lviv
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United Kingdom
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Devon
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Somerset
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Liverpool
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London
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Manchester
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Reading
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United Kingdom
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Swansea
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Vietnam
State/province [94] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00351468