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New Drug for HCV Thrombocytopenia Appears Effective In Interim Study Results
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"Efficacy and Safety of Eltrombopag, an Oral Platelet Growth Factor, in Subjects with HCV Associated Thrombocytopenia: Preliminary Results From a Phase II Dose-Ranging Study"
Reported by Jules Levin
EASL
April 26-30, 2006, Vienna, Austria
--interim study results: at the highest dose group in this preliminary 28-day study of 75 mg once daily platelet counts increased from baseline median count of 56,000 to median count at day 28 of 246,000...
John McHutchison, GSK and coauthors reported this intriguing data in a Late Breaker poster at EASL.
Background
- Thrombocytopenia is frequently observed in patients with advanced chronic liver disease (Streff et al. Hepatology. 2002;35:947-952).
- Patients with chronic hepatitis C-related thrombocytopenia may not be considered for standard therapy with pegylated interferon and ribavirin.
- Interferon-based antiviral therapy is known to cause thrombocytopenia.
- it leads to dose reduction/discontinuation in 3-6% of subjects in clinical trials (Pegasys prescribing information, 2002; Peg-Intron precscribing information, 2001).
- dose reductions of 20% or more are associated with decreased antiviral efficacy (McHutchison et al. Gastroenterology. 2002;123:1061-1069).
- Eltrombopag (SB-497115-GR) is a non-peptide oral small molecule platelet growth factor, which activates the tr=hrombopoietin (Tpo) receptor, stimulates megakaryocyte proliferation and differentiation, and increases platelet counts in healthy volunteers.
Rationale
Safety, tolerability, PK/PD were assessed in a phase I trial of eltrombopag 75 mg administered once daily for 10 days in healthy volunteers (Jenkins et al. Blood 2004; 104. Abstract 2916).
-- Eltrombopag was well tolerated and exhibited a linear pharmacokinetic profile.
-- A dose-dependent increase in platelet count was observed beginning on study day 7.
There is an unmet need for a safe and effective treatment of disease- and interferon-associated thrombocytopenia in HCV-infected patients to help facilitate optimal antiviral treatment.
Limited yet promising data with alternative thrombocytopenia agents suggest that there is a potential role for eltrombopag in HCV-infected patients (Rusti et al. 53rd AASLD 2002; Abstract 791. Ghalib et al. Hepatology).
Study Aims
Double-blind placebo controlled study to evaluate the effects of eltrombopag on platelet counts when administered once daily for 4 weeks to subjects with chronic hepatitis C related thrombocytopenia, prior to receiving antiviral therapy with pegylated interferon and ribavirin.
Assess safety and tolerability.
Methods: Eligibility Criteria
-- Male or female 18 years of age or older
-- Chronic HCV-infection (detectable HCV RNA).
-- Compensated liver disease (Child Pugh A).
-- Pre-existing thrombocytopenia: 20,000 to 70,000/uL: subjects stratified by baseline count-20,000 to 50,000u/L and >50,000 to 70,000u/L.
-- No history of thrombosis, HIV, or active infection with hepatitis B
-- results presented are from a limited preliminary analysis of 33 subjects who had completed Part 1 of the study.
SAFETY
At the time of the analysis, no SAEs have been reported at any dose level.
The most common adverse events were nausea, headaches, and diarrhea.
No patient discontinued therapy for an adverse event.
Conclusions
- High response rates were observed across all 3 active treatment arms.
- Limited interim data show potential for eltrombopag to increase platelet counts and allow subjects to initiate interferon-based antiviral therapy.
- No patients discontinued treatment due to adverse events.
- Further analysis of all subjects enrolled (n=74, to date) in Parts 1 and 2 is ongoing.
Study sponsored by GSK.
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