EXTEND (Eltrombopag Extended Dosing Study)

Purpura, Thrombocytopaenic, Idiopathic Clinical Trial

— EXTEND  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00351468
• Other study ID #: TRA105325
• Status: Completed
• Phase: Phase 3
• First received: July 10, 2006
• Last updated: March 22, 2016
• Start date: June 2006
• Est. completion date: July 2015

Study information

• Verified date: March 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 302
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Purpura
• Purpura, Thrombocytopaenic, Idiopathic
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

Drug:
• eltrombopag olamine (SB-497115-GR)
Eltrombopag at a dose up to 75mg daily

Locations

Country	Name	City	State
Australia	Novartis investigative Site	Garran	Australian Capital Territory
Australia	Novartis Investigative Site	Kogarah	New South Wales
Austria	Novartis Investigative Site	Vienna
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
China	Novartis Investigative Site	Jiang Su Province
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Tianjin
Czech Republic	Novartis Investigative Site	Brno
Czech Republic	Novartis Investigative Site	Olomouc
Czech Republic	Novartis Investigative Site	Praha 2
Denmark	Novartis Investigative Site	Odense
Finland	Novartis Investigative Site	Kuopio
France	Novartis Investigative Site	Caen cedex 9
France	Novartis Investigative Site	Créteil
France	Novartis Investigative Site	Pessac
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Giessen	Hessen
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Saarbruecken	Saarland
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki
Hong Kong	Novartis Investigative Site	Shatin, New Territories
Italy	Novartis Investigative Site	Albano Laziale (Roma)	Lazio
Italy	Novartis Investigative Site	Bologna	Emilia-Romagna
Italy	Novartis investigative Site	Milano	Lombardia
Italy	Novartis Investigative Site	Padova	Veneto
Korea, Republic of	Novartis Investigative Site	Seoul
Netherlands	Novartis Investigative Site	Amersfoort
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Den Haag
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Rotterdam
New Zealand	Novartis Investigative Site	Auckland
New Zealand	Novartis Investigative Site	Christchurch
New Zealand	Novartis Investigative Site	Grafton
New Zealand	Novartis Investigative Site	Takapuna, Auckland
Pakistan	Novartis Investigative Site	Karachi
Pakistan	Novartis Investigative Site	Lahore
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	Lima
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Slupsk
Poland	Novartis Investigative Site	Torun
Poland	Novartis Investigative Site	Wroclaw
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucharest
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis investigative Site	St Petersburg
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Presov
Slovenia	Novartis Investigative Site	Ljubljana
Spain	Novartis Investigative Site	Badalona/Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Palma de Mallorca
Spain	Novartis Investigative Site	Pamplona
Spain	Novartis Investigative Site	Santiago de Compostela
Sweden	Novartis Investigative Site	Göteborg
Sweden	Novartis Investigative Site	Stockholm
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Khon Kaen
Tunisia	Novartis investigative Site	Montfleury
Tunisia	Novartis investigative Site	Sfax
Tunisia	Novartis Investigative Site	Sousse
Tunisia	Novartis Investigative Site	Tunis
Ukraine	Novartis Investigative Site	Dnipropetrovsk
Ukraine	Novartis Investigative Site	Lviv
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Plymouth	Devon
United Kingdom	Novartis Investigative Site	Reading
United Kingdom	Novartis Investigative Site	Swansea
United Kingdom	Novartis Investigative Site	Taunton	Somerset
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Arlington	Virginia
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Brunsville	Minnesota
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Duarte	California
United States	Novartis Investigative Site	Huntsville	Alabama
United States	Novartis Investigative Site	Jonesboro	Arkansas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Lubbock	Texas
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Mobile	Alabama
United States	Novartis Investigative Site	New Orleans	Louisiana
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Peoria	Illinois
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	San Francisco	California
United States	Novartis Investigative Site	Savannah	Georgia
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Tacoma	Washington
United States	Novartis Investigative Site	Vancouver	Washington
Vietnam	Novartis Investigative Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Vietnam,  Australia,  Austria,  Canada,  China,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Greece,  Hong Kong,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Pakistan,  Peru,  Poland,  Romania,  Russian Federation,  Slovakia,  Slovenia,  Spain,  Sweden,  Taiwan,  Thailand,  Tunisia,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability parameters including, clinical laboratory tests, ocular examinations, bone marrow biopsy, and frequency of all adverse events.		For at least 2 years	Yes
Secondary	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.		For at least 2 years	No
Secondary	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.		For at least 2 years	No
Secondary	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.		For at least 2 years	No
Secondary	To describe the effect of eltrombopag on reduction and/or sparing of concomitant ITP therapies, while maintaining a platelet count = 50,000/mL.		For at least 2 years	No
Secondary	Proportion of subjects achieving stable platelet counts = 50,000/µL while remaining free of concomitant ITP medication during treatment with eltrombopag.		For at least 2 years	No
Secondary	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).		For at least 2 years	No
Secondary	Incidence and severity of signs and symptoms associated with ITP measured using the World Health Organization (WHO) bleeding scale and the ITP Bleeding Score.		For at least 2 years	No
Secondary	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:		For at least 2 years	No
Secondary	Medical Outcomes Trust Short Form 36 (SF-36v2 Acute Recall), the short form of the Motivation and Energy Scale (MEI-SF),		For at least 2 years	No
Secondary	the stand-alone symptom sub-scale FACIT-Fatigue, and relevant bleeding and bruising questions from the FACT-thrombocytopenia subscale.		For at least 2 years	No