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

Purpura, Thrombocytopaenic, Idiopathic Clinical Trial

Official title:

An Open-label Repeat Dosing Study of Eltrombopag Olamine (SB-497115-GR) in Adult Subjects, With Chronic Idiopathic Thrombocytopenic Purpura (ITP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00424177
• Other study ID #: TRA108057
• Status: Completed
• Phase: Phase 2
• First received: January 17, 2007
• Last updated: July 25, 2013
• Start date: March 2007
• Est. completion date: November 2008

Study information

• Verified date: May 2012
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This open-label, repeat dosing study, TRA108057, will evaluate the efficacy, safety and tolerability of eltrombopag, when administered in a repeat, cyclic dosing schedule. The study will describe the effect of repeated (3 cycles), intermittent dosing of eltrombopag on the pharmacodynamics and durability of eltrombopag response as measured by the peripheral platelet counts.

For more information or to see if you qualify, please visit: http://www.itpstudy.com/gov

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: November 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 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.

• Previous participation in a clinical study with eltrombopag.

• Subjects planning to have cataract surgery.

• In France, a subject is neither affiliated with nor a beneficiary of a social security category.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy 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
experimental

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Hannover	Niedersachsen
Russian Federation	GSK Investigational Site	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Germany,  Russian Federation, 

References & Publications (3)

Bussel JB, Saleh MN, Vasey SY, Mayer B, Arning M, Stone NL. Repeated short-term use of eltrombopag in patients with chronic immune thrombocytopenia (ITP). Br J Haematol. 2013 Feb;160(4):538-46. doi: 10.1111/bjh.12169. Epub 2012 Dec 24. — View Citation

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. — View Citation

This study has not been published in the scientific literature.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Complete blood count, platelet count by blood draw	Day 42 of each cycle	No
Secondary	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.	CBC, platelet counts	Up to 42 days of dosing	No
Secondary	Changes in Participants' Platelet Counts During 3 Cycles of Treatment	Changes from baseline, during on-therapy periods of a cycle, during off-therapy periods of a cycle, and within 4 weeks of permanent discontinuation of eltrombopag treatment.	Up to 1 year	No
Secondary	Number of Participants Who Required Rescue Medication	New idiopathic thrombocytopenic purpura (ITP) medication, increase dose of a concomitant ITP medication from baseline, platelet transfusion, and/or splenectomy	Up to 3 cycles of treatment including follow-up visits following last dose of eltrombopag	No
Secondary	Change in Participants Anti-platelet Antibody Levels From Baseline Through Follow-up	Change in participants' anti-platelet antibody levels was measured as the number of samples positive for at least 1 glycoprotein from baseline to follow-up. Serum glycoprotein-specific antigens: GPIIb/IIIa, Ib/IX, and Ia/IIa	Up to 1 year	No
Secondary	Number of Participants With the Indicated Bleeding Signs and Symptoms Using the World Health Organization Bleeding Scale	World health Organization (WHO) Bleeding Scale Grade 0 = no bleeding, Grade 1 = petechiae, Grade 2 = mild blood loss, Grade 3 = gross blood loss, Grade 4 = debilitating blood loss.	Baseline, on-treatment visits (Weeks 1-6), off-treatment visits (Weeks 1-4)	No
Secondary	Number of Participants With the Indicated Bleeding Signs and Symptoms Using the ITP Bleeding Score	ITP Bleeding Score: Grade 0 = no bleeding, Grade 1 = mild bleeding, Grade 2 = severe bleeding	Baseline, on-treatment visits (Weeks 1-6), off-treatment visits (Weeks 1-4)	No