Clinical trial NCT00828750: Clinical Evaluation of Eltrombopag in Chronic Idiopathic Thrombocytopenic Purpura (ITP)
Official title: Clinical Evaluation of Eltrombopag in Chronic Idiopathic Thrombocytopenic Purpura (ITP)-An Extension Study of Eltrombopag in Subjects, With Idiopathic Thrombocytopenic Purpura (ITP), Previously Enrolled in an Eltrombopag Study TRA108109 (NCT00540423)-<Phase III Study>
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Thrombocytopenic Purpura
Purpura, Thrombocytopenic, Idiopathic
Keywords: eltrombopag
thrombopoietin receptor agonist
ITP
blood platelet
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-01-26
Enrollment: 19
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: An open-label, dose-adjustment extension study to evaluate the safety and efficacy of eltrombopag for treatment of subjects with ITP who have previously been enrolled in the eltrombopag trial TRA108109 (NCT00540423).


Eligibility criteria: Inclusion Criteria:

* Subject has signed and dated written informed consent.
* Subject (\>=20 years) diagnosed with ITP.
* Subject previously enrolled in TRA108109 (NCT00540423) must have completed the treatment and follow-up periods as defined in that protocol.
* Subject has no intercurrent medical event at risk of thrombosis such as thrombophilia.
* Prolongation of prothrombin time and activated partial thromboplastin time (aPTT) must be within 1.2 times the upper limit of the normal range with no history of hypercoagulable state.
* A complete blood count (CBC), within the reference range, with the following exceptions:
* Hemoglobin: patients with haemoglobin level \< the lower limit of normal are eligible for inclusion if hemorrhage is present.
* Neutrophil count \>= 1,500/L (1.5x10E9/L) is required for inclusion.
* The following clinical chemistries MUST NOT exceed 1.2 times the upper limit of the normal reference range: creatinine, total bilirubin and alkaline phosphatase.
* The following clinical chemistries MUST NOT exceed 2 times the upper limit of the normal reference range: ALT and AST.
* Albumin must be not less than 80% of the lower limit of normal.
* Female subjects must either be:
* of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal \> 1 year), or
* of childbearing potential and have a negative pregnancy test and agree to use contraceptive methods specified in the GSK List of Highly Effective Methods for Avoidance of Pregnancy from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:
* Reticulocyte count within the reference range or elevated in case of bleeding.

Exclusion Criteria:

* Any severe medical condition (cardiac, hepatic or renal disorder) other than chronic ITP. (Note: "Severe" is defined as \>= Grade 3 as a rule according to the "Classification of the Severity of Adverse Experiences (PAB/SD Notification No.80, dated 29 June 1992)
* History of suspected or confirmed arterial or venous thrombosis (e.g., myocardial infarction, deep vein thrombosis) within the last 1 year.
* History of drug/alcohol abuse or dependence within the last 1 year.
* Suspected blood disorder other than ITP.
* Suspected platelet aggregation abnormality.
* Suspected cyclic thrombocytopenia.
* Suspected Evans Syndrome.
* Subjects who met the GSK Liver Stopping Criteria in the previous eltrombopag study TRA108109 (NCT00540423).
* Current or history of HIV infection or hepatitis B virus or hepatitis C virus infections.
* Current malignancy or history of malignancy that was treated with chemotherapy or radiotherapy.
* Female subjects who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period.
* Subjects who are deemed unsuitable for the study by the investigator (or subinvestigator).
* Treatment with an investigational drug within 30 days preceding the first dose of study medication.
* Pre-existing cardiovascular disease, or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation).

Primary outcomes:
measure: Number of Participants Experiencing an Adverse Event (AE) and/or Serious Adverse Event (SAE) Within the Indicated Category
timeFrame: From Baseline (Day 1) to last dose of eltrombopag/early withdrawal visit (up to 981 days)
Secondary outcomes:
measure: Percentage of Participants Achieving a Platelet Count Greater Than or Equal to 50 Giga Unit (10^9) Per Liter (Gi/L) and Less Than or Equal to 400 Gi/L
timeFrame: Baseline; Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, and 136; and last visit/early withdrawal visit (up to Day 982)
measure: Median Platelet Counts
timeFrame: Baseline; Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, and 136; and last visit/early withdrawal visit (up to Day 982)
measure: Percentage of Participants With a Given Maximum Number of Weeks of Continuous Platelet Count Evaluation Greater Than or Equal to 50 Gi/L and Greater Than or Equal to Twice the Baseline Count Categorized by Weeks on Study Medication (Med.)
timeFrame: From Baseline (Day 1) to last dose of eltrombopag/early withdrawal visit (up to 981 days)
measure: Median Number of Maximum Continuous Weeks of Maintaining Platelet Counts Greater Than or Equal to 50 Gi/L and Greater Than or Equal to Twice the Baseline Count at Three-Month Intervals
timeFrame: 3, 6, 9, 12, 15, 18, 21, 24, 27, and 30 months (13, 26, 39, 52, 65, 78, 91, 104, 117, and 130 weeks)
measure: Percentage of Participants Experiencing Any Bleeding Episode After Dosing With Study Medication
timeFrame: Baseline; Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, and 136; and last visit/early withdrawal visit (up to Day 982)
measure: Percentage of Participants With a Reduction in Use of Baseline Idiopathic Thrombocytopenic Purpura (ITP) Medication
timeFrame: From Baseline (Day 1) to last dose of eltrombopag/early withdrawal visit (up to 981 days)
measure: Percentage of Participants Initiating Rescue Medication/Treatment During On-Therapy
timeFrame: From Baseline (Day 1) to last dose of eltrombopag/early withdrawal visit (up to 981 days)
Other outcomes:
Locations:
city: Gifu
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Katsutani S, Tomiyama Y, Kimura A, Miyakawa Y, Okamoto S, Okoshi Y, Ninomiya H, Kosugi H, Ishii K, Ikeda Y, Hattori T, Katsura K, Kanakura Y. Oral eltrombopag for up to three years is safe and well-tolerated in Japanese patients with previously treated chronic immune thrombocytopenia: an open-label, extension study. Int J Hematol. 2013 Sep;98(3):323-30. doi: 10.1007/s12185-013-1401-1. Epub 2013 Jul 30.