EXTEND (Eltrombopag Extended Dosing Study)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00351468
First received: July 10, 2006
Last updated: July 3, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Purpura, Thrombocytopaenic, Idiopathic
Drug: eltrombopag olamine (SB-497115-GR)
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety and tolerability parameters including, clinical laboratory tests, ocular examinations, bone marrow biopsy, and frequency of all adverse events. [ Time Frame: For at least 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • To describe the effect of eltrombopag on reduction and/or sparing of concomitant ITP therapies, while maintaining a platelet count ≥ 50,000/mL. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving stable platelet counts ≥ 50,000/µL while remaining free of concomitant ITP medication during treatment with eltrombopag. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • Incidence and severity of signs and symptoms associated with ITP measured using the World Health Organization (WHO) bleeding scale and the ITP Bleeding Score. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • 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: [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • Medical Outcomes Trust Short Form 36 (SF-36v2 Acute Recall), the short form of the Motivation and Energy Scale (MEI-SF), [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]
  • the stand-alone symptom sub-scale FACIT-Fatigue, and relevant bleeding and bruising questions from the FACT-thrombocytopenia subscale. [ Time Frame: For at least 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 302
Study Start Date: June 2006
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eltrombopag
Open-label eltrombopag
Drug: eltrombopag olamine (SB-497115-GR)
Eltrombopag at a dose up to 75mg daily
Other Name: eltrombopag olamine (SB-497115-GR)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00351468

  Hide Study Locations
Locations
United States, Alabama
GSK Investigational Site
Huntsville, Alabama, United States, 35805
GSK Investigational Site
Mobile, Alabama, United States, 36608
United States, Arkansas
GSK Investigational Site
Jonesboro, Arkansas, United States, 72401
United States, California
GSK Investigational Site
Duarte, California, United States, 91010
GSK Investigational Site
Los Angeles, California, United States, 90033
GSK Investigational Site
San Francisco, California, United States, 94143
United States, Florida
GSK Investigational Site
Miami, Florida, United States, 33136
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30341
GSK Investigational Site
Savannah, Georgia, United States, 31405
United States, Illinois
GSK Investigational Site
Peoria, Illinois, United States, 61614
United States, Louisiana
GSK Investigational Site
New Orleans, Louisiana, United States, 70115
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02114
United States, Michigan
GSK Investigational Site
Detroit, Michigan, United States, 48202
United States, Minnesota
GSK Investigational Site
Brunsville, Minnesota, United States, 55337
United States, New Mexico
GSK Investigational Site
Albuquerque, New Mexico, United States, 87109
United States, New York
GSK Investigational Site
New York, New York, United States, 10021
United States, Ohio
GSK Investigational Site
Cleveland, Ohio, United States, 44106
United States, Oregon
GSK Investigational Site
Portland, Oregon, United States, 97227
United States, Texas
GSK Investigational Site
Lubbock, Texas, United States, 79410
United States, Virginia
GSK Investigational Site
Arlington, Virginia, United States, 22205
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98109
GSK Investigational Site
Tacoma, Washington, United States, 98405
GSK Investigational Site
Vancouver, Washington, United States, 98684
Australia, Australian Capital Territory
GSK Investigational Site
Garran, Australian Capital Territory, Australia, 2606
Australia, New South Wales
GSK Investigational Site
Kogarah, New South Wales, Australia, 2217
Austria
GSK Investigational Site
Vienna, Austria, A-1090
Canada, Ontario
GSK Investigational Site
Hamilton, Ontario, Canada, L8S 4K1
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H3T 1E2
GSK Investigational Site
Montreal, Quebec, Canada, H2L 4M1
China
GSK Investigational Site
Jiang Su Province, China, 215006
GSK Investigational Site
Shanghai, China, 200025
GSK Investigational Site
Tianjin, China, 300020
Czech Republic
GSK Investigational Site
Brno, Czech Republic, 625 00
GSK Investigational Site
Olomouc, Czech Republic, 775 20
GSK Investigational Site
Praha 2, Czech Republic, 128 20
Denmark
GSK Investigational Site
Odense, Denmark, 5000
Finland
GSK Investigational Site
Kuopio, Finland, 70210
France
GSK Investigational Site
Caen cedex 9, France, 14033
GSK Investigational Site
Créteil, France, 94010
GSK Investigational Site
Pessac, France, 33604
Germany
GSK Investigational Site
Muenchen, Bayern, Germany, 80639
GSK Investigational Site
Bad Nauheim, Hessen, Germany, 61231
GSK Investigational Site
Giessen, Hessen, Germany, 35392
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30159
GSK Investigational Site
Saarbruecken, Saarland, Germany, 66113
GSK Investigational Site
Berlin, Germany, 13353
Greece
GSK Investigational Site
Athens, Greece, 10676
GSK Investigational Site
Athens, Greece, 11525
GSK Investigational Site
Thessaloniki, Greece, 57010
Hong Kong
GSK Investigational Site
Shatin, New Territories, Hong Kong
Italy
GSK Investigational Site
Bologna, Emilia-Romagna, Italy, 40138
GSK Investigational Site
Albano Laziale (Roma), Lazio, Italy, 00041
GSK Investigational Site
Milano, Lombardia, Italy, 20132
GSK Investigational Site
Padova, Veneto, Italy, 35128
Korea, Republic of
GSK Investigational Site
Seoul, Korea, Republic of, 136-705
Netherlands
GSK Investigational Site
Amersfoort, Netherlands, 3816 CP
GSK Investigational Site
Amsterdam, Netherlands, 1105 AZ
GSK Investigational Site
Den Haag, Netherlands, 2545 CH
GSK Investigational Site
Nijmegen, Netherlands, 6525 GA
GSK Investigational Site
Rotterdam, Netherlands, 3015 GE
New Zealand
GSK Investigational Site
Auckland, New Zealand, 2024
GSK Investigational Site
Christchurch, New Zealand, 8011
GSK Investigational Site
Grafton, New Zealand, 1001
GSK Investigational Site
Takapuna, Auckland, New Zealand, 0622
Pakistan
GSK Investigational Site
Karachi, Pakistan, 75300
GSK Investigational Site
Lahore, Pakistan, 54600
Peru
GSK Investigational Site
Lima, Peru, Lima 27
GSK Investigational Site
Lima, Peru, Lima 41
Poland
GSK Investigational Site
Bialystok, Poland, 15-276
GSK Investigational Site
Lodz, Poland, 93-510
GSK Investigational Site
Lublin, Poland, 20-081
GSK Investigational Site
Slupsk, Poland, 76-200
GSK Investigational Site
Torun, Poland, 87-100
GSK Investigational Site
Wroclaw, Poland, 50-367
Romania
GSK Investigational Site
Bucharest, Romania, 050098
GSK Investigational Site
Bucharest, Romania, 022328
Russian Federation
GSK Investigational Site
Moscow, Russian Federation, 105 229
GSK Investigational Site
Moscow, Russian Federation, 125167
GSK Investigational Site
Novosibirsk, Russian Federation, 630087
GSK Investigational Site
St Petersburg, Russian Federation, 193024
Slovakia
GSK Investigational Site
Kosice, Slovakia, 041 90
GSK Investigational Site
Presov, Slovakia, 080 01
Slovenia
GSK Investigational Site
Ljubljana, Slovenia, 1000
Spain
GSK Investigational Site
Badalona, Spain, 08916
GSK Investigational Site
Barcelona, Spain, 08025
GSK Investigational Site
Madrid, Spain, 28007
GSK Investigational Site
Madrid, Spain, 28006
GSK Investigational Site
Palma de Mallorca, Spain, 07014
GSK Investigational Site
Pamplona, Spain, 31008
GSK Investigational Site
Santiago de Compostela, Spain, 15706
Sweden
GSK Investigational Site
Göteborg, Sweden, SE-413 45
GSK Investigational Site
Stockholm, Sweden, SE 171 76
Taiwan
GSK Investigational Site
Taipei, Taiwan, 100
Thailand
GSK Investigational Site
Bangkok, Thailand, 10330
GSK Investigational Site
Khon Kaen, Thailand, 40002
Tunisia
GSK Investigational Site
Montfleury, Tunisia, 1008
GSK Investigational Site
Sfax, Tunisia, 3029
GSK Investigational Site
Sousse, Tunisia, 4000
GSK Investigational Site
Tunis, Tunisia, 1008
Ukraine
GSK Investigational Site
Dnipropetrovsk, Ukraine, 49102
GSK Investigational Site
Lviv, Ukraine, 79044
United Kingdom
GSK Investigational Site
Plymouth, Devon, United Kingdom, PL6 8DH
GSK Investigational Site
Taunton, Somerset, United Kingdom, TA1 5DA
GSK Investigational Site
Liverpool, United Kingdom, L7 8XP
GSK Investigational Site
London, United Kingdom, E1 1BB
GSK Investigational Site
London, United Kingdom, NW1 2PG
GSK Investigational Site
Manchester, United Kingdom, M13 9WL
GSK Investigational Site
Reading, United Kingdom, RG1 5AN
GSK Investigational Site
Swansea, United Kingdom, SA6 6NL
Vietnam
GSK Investigational Site
Ho Chi Minh, Vietnam
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00351468     History of Changes
Other Study ID Numbers: TRA105325
Study First Received: July 10, 2006
Last Updated: July 3, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
eltrombopag olamine
SB-497115-GR
idiopathic thrombocytopenic purpura
thrombocytopenia
ITP
platelets

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases

ClinicalTrials.gov processed this record on July 26, 2014