SB497115 (Oral Thrombopoietin Receptor Agonist) Versus Placebo In Adults With Thrombocytopenia Due To Hepatitis C

Hepatitis C Clinical Trial

Official title:

A Double-Blind, Randomized, Placebo-Controlled, Multi-Centre, Dose-Ranging, Parallel Group, Phase II Study to Assess Efficacy, Safety/Tolerability, and Pharmacokinetics of a Thrombopoietin Receptor Agonist, SB-497115-GR, When Administered as 30, 50, and 75 mg Once Daily for 12 Weeks in Subjects With

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00110799
• Other study ID #: TPL102357
• Status: Completed
• Phase: Phase 2
• First received: May 13, 2005
• Last updated: May 31, 2012
• Start date: April 2005
• Est. completion date: November 2006

Study information

• Verified date: March 2011
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

SB497115 is an oral agent which activates the thrombopoietin receptor and increases platelet counts in healthy volunteers. This study is examining several different doses of SB497115 as a treatment for patients with chronic hepatitis C-related thrombocytopenia who are potential candidates for antiviral treatment with pegylated interferon and ribavirin. The study will be conducted in two phases, Parts 1 and 2. In Part 1, study subjects will be randomized to 4 weeks of SB-497115-GR or placebo administered daily without antiviral therapy. Subjects who successfully complete Part 1 (platelet count 70,000/µL for Pegasys and platelet count 100,000/µL for PEG-Intron) will then proceed to Part 2. In Part 2, subjects will receive an additional 8 weeks of SB-497115-GR or placebo administered daily with antiviral therapy.

Description:

A Double-Blind, Randomized, Placebo-Controlled, Multi-Centre, Dose-Ranging, Parallel Group, Phase II Study to Assess Efficacy, Safety/Tolerability, and Pharmacokinetics of a Thrombopoietin Receptor Agonist, SB-497115-GR, when Administered as 30, 50, and 75 mg Once Daily for 12 weeks in Subjects with Chronic Hepatitis C-Related Thrombocytopenia who are Potential Candidates for Antiviral Treatment with Pegylated Interferon and Ribavirin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: November 2006
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Chronic low platelet count between 20,000 and <70,000/µL.

• Prior liver biopsy indicating chronic hepatitis within the previous 5 years or radiographic evidence of cirrhosis and / or endoscopic evidence of non-bleeding esophageal or gastric varices.

Exclusion criteria:

• History of heart attack or abnormal heart function.

• History of thrombosis within 1 year.

• History of alcohol or drug abuse or dependence within 1 year.

• Use of aspirin, aspirin-containing compounds, salicylates, antacids.

• History of HIV infection or active infection with Hepatitis B or C.

• Females who are pregnant.

• Patients using non-steroidal anti-inflammatory drugs during the study and within 3 weeks prior to starting the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Thrombocytopenia
• Thrombocytosis

Intervention

Drug:
• SB497115
Approximately 160 subjects will be randomized equally to one of four treatment groups of approximately 40 subjects (A-D). Subjects will receive oral tablets of SB-497115-GR at 30mg, 50 mg, 75 mg or placebo administered once daily for a total of 12 weeks beginning 4 weeks prior to initiating 8 weeks of antiviral therapy and for 8 weeks during weekly antiviral therapy.

Other:
• Placebo
Placebo administered orally daily for 12 weeks beginning 4 weeks prior to initiating 8 weeks of antiviral therapy and for 8 weeks during weekly antiviral therapy.

Locations

Country	Name	City	State
France	GSK Investigational Site	Clermont Ferrand Cédex 1
France	GSK Investigational Site	Clichy Cedex
France	GSK Investigational Site	Lyon
France	GSK Investigational Site	Lyon Cedex 02
France	GSK Investigational Site	Marseille Cedex 08
France	GSK Investigational Site	Nice Cedex 03
France	GSK Investigational Site	Paris Cedex 12
France	GSK Investigational Site	Pessac Cedex
France	GSK Investigational Site	Vandoeuvre Les Nancy
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Homburg	Saarland
Puerto Rico	GSK Investigational Site	San Juan
United Kingdom	GSK Investigational Site	Bristol	Gloucestershire
United Kingdom	GSK Investigational Site	Glasgow	Lanarkshire
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Nottingham	Nottinghamshire
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Fairfax	Virginia
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  France,  Germany,  Puerto Rico,  United Kingdom, 

References & Publications (1)

McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M, Sigal S, Bourliere M, Berg T, Gordon SC, Campbell FM, Theodore D, Blackman N, Jenkins J, Afdhal NH; TPL102357 Study Group. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007 Nov 29;357(22):2227-36. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment response, assessed by the proportion of subjects with a shift from baseline platelet count (20, 000 to <70,000µL) to =100,000/µL after 4 weeks of study treatment.		4 weeks	No
Secondary	Mean increase in platelet counts and markers of thrombopoiesis. Safety and tolerability, population PK, pharmacodynamics. Effect of antiviral outcome measures during and after therapy.		4 weeks	No