Repeated Exposure to Eltrombopag in Adults With Idiopathic Thrombocytopenic Purpura (REPEAT)

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00424177
• Date of registration: 17/01/2007
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Repeated Exposure to Eltrombopag in Adults With Idiopathic Thrombocytopenic Purpura (REPEAT)
• Scientific title: An Open-label Repeat Dosing Study of Eltrombopag Olamine (SB-497115-GR) in Adult Subjects, With Chronic Idiopathic Thrombocytopenic Purpura (ITP)
• Date of first enrolment: March 2007
• Target sample size: 66
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00424177
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Australia, Canada, Germany, India, Korea, Republic of, Netherlands, Russian Federation, Spain, Tunisia, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

Subjects eligible for enrolment in the study must meet all of the following criteria:

- Subject has signed and dated a written inform consent.

- Adults (=18 years) diagnosed with chronic ITP according to the American Society of
Hematology/British Committee for Standards in Hematology guidelines, and a platelet
count between =20 Gi/L and =50 Gi/L on Day 1 (or within 24 hours prior to dosing on
Day 1). In addition, a peripheral blood smear should support the diagnosis of ITP with
no evidence of other causes of thrombocytopenia (e.g. pseudothrombocytopenia,
myelodysplasia). The physical examination should not suggest any disease which may
cause thrombocytopenia other than ITP.

- Subjects who have previously received one or more prior ITP therapies. Previous
treatments for ITP include but are not limited to corticosteroids, immunoglobulins,
azathioprine, danazol, cyclophosphamide and/or rituximab.

- Subjects must have either initially responded (platelet count >100 Gi/L) to a previous
ITP therapy or have had a bone marrow biopsy consistent with ITP within 3 years to
rule out myelodysplastic syndromes or other causes of thrombocytopenia.

- It is important to clearly differentiate the effect of eltrombopag on platelet count
from the treatment effects of prior and concomitant ITP therapies. Therefore:

1. Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have been
completed at least 1 week prior to randomization 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.

2. Subjects treated with concomitant ITP medication (e.g. corticosteroids or
azathioprine) must be receiving a dose that has been stable for a 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 randomization.

- Prothrombin time and activated partial thromboplastin time must be within 80 to 120%
of normal range with no history of hypercoagulable state.

- A complete blood count (CBC), within the reference range (including differential not
indicative of a disorder other than ITP), with the following exceptions:

- Platelet count between =20 Gi/L and =50 Gi/L on Day 1 (or within 24 hours of Day 1) is
required for inclusion.

- Hemoglobin: Subjects with hemoglobin levels between 10g/dL (100g/L) and the lower
limit of normal are eligible for inclusion, if anemia is clearly attributable to ITP
(excessive blood loss).

- Absolute Neutrophil Count (ANC ) >1500/mL (1.5 x 10^9/L) is required for inclusion
(elevated White Blood Cells/ANC above the reference range due to steroid treatment is
acceptable).

- The following clinical chemistries MUST NOT exceed the normal reference range by more
than 20%: creatinine, Alanine aminotransferase, Aspartate aminotransferase, total
bilirubin, total albumin and alkaline phosphatase.

- 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 of one of
the following acceptable methods of contraception 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
and intends to complete the study as planned.

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 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,
Antithrombin III deficiency, etc), or any other family history of arterial or venous
thrombosis.

- Pre-existing cardiovascular disease (congestive heart failure, New York Heart
Association 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 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 Non Steroidal Anti Inflammatory Drugs) 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 human immunodeficiency virus (HIV) infection,
anti-phospholipid antibody syndrome, chronic hepatitis B infection, hepatitis C virus
infection, or any


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Purpura, Thrombocytopaenic, Idiopathic

Intervention(s)

Drug: eltrombopag

Primary Outcome(s)

Number of Participants Who Responded (Platelet Count >=50 Gi/L and >=2x Baseline) to Eltrombopag Treatment in Cycle 2 or Cycle 3 Given Participants Responded in Cycle 1 [Time Frame: Day 42 of each cycle]

Secondary Outcome(s)

Change in Participants Anti-platelet Antibody Levels From Baseline Through Follow-up [Time Frame: Up to 1 year]

Changes in Participants' Platelet Counts During 3 Cycles of Treatment [Time Frame: Up to 1 year]

Number of Participants Who Required Rescue Medication [Time Frame: Up to 3 cycles of treatment including follow-up visits following last dose of eltrombopag]

Number of Participants Who Responded (Platelet Count Greater Than or Equal to 50 Gi/L and at Least 2x Baseline) for at Least 80 Percent of Their On-therapy Assessments During Weeks 2-6. [Time Frame: Up to 42 days of dosing]

Number of Participants With the Indicated Bleeding Signs and Symptoms Using the ITP Bleeding Score [Time Frame: Baseline, on-treatment visits (Weeks 1-6), off-treatment visits (Weeks 1-4)]

Number of Participants With the Indicated Bleeding Signs and Symptoms Using the World Health Organization Bleeding Scale [Time Frame: Baseline, on-treatment visits (Weeks 1-6), off-treatment visits (Weeks 1-4)]

Secondary ID(s)

TRA108057

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/08/2009
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00424177