EXTEND (Eltrombopag Extended Dosing Study)

NCT00351468 | Completed Phase 3 Results

• 1 other identifier: TRA105325
• Study Type: interventional
• Target: 302
• Locations: 29 countries
• Sites: 107

Brief 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/μL will be investigated.

Conditions

Purpura, Thrombocytopaenic, Idiopathic

Keywords

eltrombopag olamine; SB-497115-GR; idiopathic thrombocytopenic purpura; thrombocytopenia; ITP; platelets

Outcome Measures

Primary Outcomes (1)

• Overall Summary of On-Therapy Adverse Events (Safety Population)

  All safety evaluation findings considered to be adverse events are reported in the Adverse Event section.

  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 Outcomes (10)

• Subjects Achieving Maximum Platelet Counts Greater Than or Equal to 30 Gi/L or 50 Gi/L in the Absence of Rescue Medication

  Baseline up to 2 years

• Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication

  Baseline up to Year 7/Week 364

• 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

  Baseline up to 2 years

• Number of Participants With Reduction and/or Sparing of Concomitant ITP Therapies, While Maintaining a Platelet Count ≥ 50,000/mL.

  Baseline up to 2 years

• Number of Subjects Who Required Rescue Therapy During Treatment With Eltrombopag.

  Baseline up to 2 years

Study Arms (1)

Eltrombopag

EXPERIMENTAL

Open-label eltrombopag

Drug: eltrombopag olamine (SB-497115-GR)

Interventions

eltrombopag olamine (SB-497115-GR) DRUG

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.

Eltrombopag

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (110)

Novartis Investigative Site

Huntsville, Alabama, 35805, United States

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Mobile, Alabama, 36608, United States

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Jonesboro, Arkansas, 72401, United States

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Duarte, California, 91010, United States

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Los Angeles, California, 90033, United States

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San Francisco, California, 94143, United States

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Miami, Florida, 33136, United States

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Atlanta, Georgia, 30341, United States

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Savannah, Georgia, 31405, United States

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Peoria, Illinois, 61614, United States

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New Orleans, Louisiana, 70115, United States

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Boston, Massachusetts, 02114, United States

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Detroit, Michigan, 48202, United States

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Brunsville, Minnesota, 55337, United States

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Albuquerque, New Mexico, 87109, United States

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New York, New York, 10021, United States

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Cleveland, Ohio, 44106, United States

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Portland, Oregon, 97227, United States

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Lubbock, Texas, 79410, United States

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Arlington, Virginia, 22205, United States

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Seattle, Washington, 98109, United States

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Tacoma, Washington, 98405, United States

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Vancouver, Washington, 98684, United States

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Garran, Australian Capital Territory, 2606, Australia

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Kogarah, New South Wales, 2217, Australia

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Vienna, A-1090, Austria

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Hamilton, Ontario, L8S 4K1, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Jiang Su Province, 215006, China

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Shanghai, 200025, China

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Tianjin, 300020, China

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Brno, 625 00, Czechia

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Olomouc, 775 20, Czechia

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Prague, 128 20, Czechia

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Odense, 5000, Denmark

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Kuopio, 70210, Finland

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Caen, 14033, France

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Créteil, 94010, France

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Pessac, 33604, France

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Munich, Bavaria, 80639, Germany

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Giessen, Hesse, 35392, Germany

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Hanover, Lower Saxony, 30159, Germany

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Hanover, Lower Saxony, 30625, Germany

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Saarbrücken, Saarland, 66113, Germany

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Berlin, State of Berlin, 13353, Germany

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Athens, 10676, Greece

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Athens, 11525, Greece

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Thessaloniki, 57010, Greece

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Shatin, New Territories, Hong Kong

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Bologna, Emilia-Romagna, 40138, Italy

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Albano Laziale (Roma), Lazio, 00041, Italy

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Milan, Lombardy, 20132, Italy

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Padua, Veneto, 35128, Italy

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Amersfoort, 3816 CP, Netherlands

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Amsterdam, 1105 AZ, Netherlands

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Nijmegen, 6525 GA, Netherlands

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Rotterdam, 3015 GE, Netherlands

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The Hague, 2545 CH, Netherlands

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Auckland, 2024, New Zealand

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Christchurch, 8011, New Zealand

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Grafton, 1001, New Zealand

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Takapuna, Auckland, 0622, New Zealand

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Karachi, 75300, Pakistan

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Lahore, 54600, Pakistan

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Lima, Lima Province, Lima 41, Peru

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Lima, Lima 27, Peru

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Bialystok, 15-276, Poland

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Lodz, 93-510, Poland

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Lublin, 20-081, Poland

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Słupsk, 76-200, Poland

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Torun, 87-100, Poland

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Wroclaw, 50-367, Poland

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Bucharest, 022328, Romania

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Bucharest, 050098, Romania

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Moscow, 105 229, Russia

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Moscow, 125167, Russia

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Novosibirsk, 630087, Russia

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Saint Petersburg, 193024, Russia

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Košice, 041 90, Slovakia

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Prešov, 080 01, Slovakia

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Ljubljana, 1000, Slovenia

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Seoul, 136-705, South Korea

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Badalona/Barcelona, 08916, Spain

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Barcelona, 08025, Spain

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Madrid, 28006, Spain

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Madrid, 28007, Spain

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Palma de Mallorca, 07014, Spain

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Pamplona, 31008, Spain

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Santiago de Compostela, 15706, Spain

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Gothenburg, SE-413 45, Sweden

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Stockholm, SE 171 76, Sweden

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Taipei, 100, Taiwan

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Bangkok, 10330, Thailand

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Khon Kaen, 40002, Thailand

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Montfleury, 1008, Tunisia

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Sfax, 3029, Tunisia

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Sousse, 4000, Tunisia

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Tunis, 1008, Tunisia

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Dnipropetrovsk, 49102, Ukraine

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Lviv, 79044, Ukraine

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Plymouth, Devon, PL6 8DH, United Kingdom

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Taunton, Somerset, TA1 5DA, United Kingdom

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Liverpool, L7 8XP, United Kingdom

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London, E1 1BB, United Kingdom

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London, NW1 2PG, United Kingdom

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Manchester, M13 9WL, United Kingdom

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Reading, RG1 5AN, United Kingdom

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Swansea, SA6 6NL, United Kingdom

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Ho Chi Minh City, Vietnam

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Related Publications (5)

• Wong RSM, Saleh MN, Khelif A, Salama A, Portella MSO, Burgess P, Bussel JB. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017 Dec 7;130(23):2527-2536. doi: 10.1182/blood-2017-04-748707. Epub 2017 Oct 17.

  PMID: 29042367 DERIVED

• Tarantino MD, Fogarty P, Mayer B, Vasey SY, Brainsky A. Efficacy of eltrombopag in management of bleeding symptoms associated with chronic immune thrombocytopenia. Blood Coagul Fibrinolysis. 2013 Apr;24(3):284-96. doi: 10.1097/MBC.0b013e32835fac99.

  PMID: 23492914 DERIVED

• Saleh MN, Bussel JB, Cheng G, Meyer O, Bailey CK, Arning M, Brainsky A; EXTEND Study Group. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood. 2013 Jan 17;121(3):537-45. doi: 10.1182/blood-2012-04-425512. Epub 2012 Nov 20.

  PMID: 23169778 DERIVED

• Fogarty PF, Tarantino MD, Brainsky A, Signorovitch J, Grotzinger KM. Selective validation of the WHO Bleeding Scale in patients with chronic immune thrombocytopenia. Curr Med Res Opin. 2012 Jan;28(1):79-87. doi: 10.1185/03007995.2011.644849. Epub 2011 Dec 20.

  PMID: 22117897 DERIVED

• Signorovitch J, Brainsky A, Grotzinger KM. Validation of the FACIT-fatigue subscale, selected items from FACT-thrombocytopenia, and the SF-36v2 in patients with chronic immune thrombocytopenia. Qual Life Res. 2011 Dec;20(10):1737-44. doi: 10.1007/s11136-011-9912-9. Epub 2011 May 1.

  PMID: 21533818 DERIVED

MeSH Terms

Conditions

Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Purpura, Thrombocytopenic; Thrombotic Microangiopathies; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2006
• First Posted: July 12, 2006
• Study Start: June 1, 2006
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: April 17, 2017
• Results First Posted: April 17, 2017

Record last verified: 2017-03

Locations

NL (5); UA (2); FI (1); PE (2); TW (1); VN (1); PL (6); AU (2); TU (4); DK (1); FR (3); HK (1); KR (1); CA (3); CN (3); IT (4); GB (8); CZ (3); GR (3); US (23); NZ (4); SL (1); SE (2); DE (6); RU (4); RO (2); PA (2); ES (7); TH (2)