Clinical Evaluation of SB-497115-GR in Chronic Idiopathic Thrombocytopenic Purpura (ITP)

Phase 3

Completed

Conditions: Purpura, Thrombocytopenic, Idiopathic
Chronic Idiopathic Thrombocytopenic Purpura

Interventions: Drug: SB-497115-GR 12.5mg
Drug: SB-497115-GR 12.5mg matching placebo
Drug: SB-497115-GR 25mg
Drug: SB-497115-GR 50 mg

Registration Number: NCT00540423

Lead Sponsor: GlaxoSmithKline

Brief Summary: This is a Phase II/III multicenter study comprising of the double-blind, followed by open-label phases to evaluate and compare the efficacy and tolerability of eltrombopag (SB-497115-GR) in chronic ITP patients

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SB-497115-GR group	SB-497115-GR 12.5mg	Subject will initiate treatment with SB-497115-GR 12.5mg once a day. Based on the subjects platelet count at each visit, the dose of SB-497115-GR may be adjusted at 12.5mg, 25mg or 50mg.
placebo group	SB-497115-GR 12.5mg matching placebo	Subject will initiate treatment with SB-497115-GR 12.5mg matching placebo once a day. Based on the subjects platelet count at each visit, the dose of SB-497115-GR 12.5mg matching placebo may be increased to 2 tablet of SB-497115-GR 12.5mg matching placebo.
SB-497115-GR group	SB-497115-GR 50 mg	Subject will initiate treatment with SB-497115-GR 12.5mg once a day. Based on the subjects platelet count at each visit, the dose of SB-497115-GR may be adjusted at 12.5mg, 25mg or 50mg.
SB-497115-GR group	SB-497115-GR 25mg	Subject will initiate treatment with SB-497115-GR 12.5mg once a day. Based on the subjects platelet count at each visit, the dose of SB-497115-GR may be adjusted at 12.5mg, 25mg or 50mg.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants for Whom at Least 75% of Their Assessments During the Course of 26 Weeks of SB-497115-GR Treatment Met the Definition of Responders	Week 26	A responder was defined as a participant with a platelet count within the target range (\>=50 x 10\^9/Liter and \<=400 x 10\^9/Liter). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.
Number of Responders at Week 6	Week 6	A responder was defined as a participant with a platelet count within the target range (\>=50 x 10\^9/Liter and \<=400 x 10\^9/Liter).

Secondary Outcome Measures

Name	Time	Method
Number of Participants at Baseline and Days 8, 15, 22, 29, 36, and 43 of Treatment by Platelet Count Category	Baseline and Days 8, 15, 22, 29, 36, and 43	Blood taken from peripheral blood vessels was used for the measurement of platelet counts.
Number of Participants Assessed as Responders in at Least 4 Assessments Between Weeks 2 and 6	Weeks 2 through 6	A responder was defined as a participant with a platelet count within the target range (\>=50 x 10\^9/Liter and \<=400 x 10\^9/Liter) at at least 4 out of 5 scheduled visits.
Percentage of Responders at Each Visit	Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26	A responder was defined as a participant with a platelet count within the target range (\>=50 x 10\^9/Liter and \<=400 x 10\^9/Liter). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.
Percentage of Participants With Bleeding Episodes Since the Last Visit	Days 1, 8, 15, 22, 29, 36, and 43	When abnormal bleeding(s) was found since the last visit, it was recorded as a bleeding episode(s).
Mean Platelet Counts of Participants at Each Visit	Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26	Blood taken from peripheral blood vessels was used for the measurement of platelet counts. Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.
Pharmacokinetics of SB-497115-GR, Cmax	Week 9 or 10	Cmax: Peak plasma concentration of SB-497115
Pharmacokinetics of SB-497115-GR, Tmax	Week 9 or 10	tmax: Time when Cmax was achieved
Mean Total Time for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter	Weeks 1 through 26	Total time is measured as the cumulative number of days over which platelet counts were maintained within the target range (\>=50 x 10\^9/Liter and \<=400 x 10\^9/Liter). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.
Percentage of Participants With Bleeding Episode Since the Last Visit	Days 1, 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26	When abnormal bleeding(s) was found since the last visit, it was recorded as a bleeding episode(s). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.
Pharmacokinetics of SB-497115-GR, Lambda z	Week 9 or 10	Lambda z is first order rate constant associated with the terminal portion of the plasma concentration curve.
Pharmacokinetics of SB-497115-GR, CL/F	Week 9 or 10	CL/F: CL is an estimate of the total body clearance, and F is the fraction of dose absorbed.
Mean Platelet Count at Each Visit	Baseline and Days 8, 15, 22, 29, 36, and 43	Blood taken from peripheral blood vessels was used for the measurement of platelet counts.
Mean Change From Baseline in Platelet Counts at Each Visit	Baseline; Days 8, 15, 22, 29, 36, and 43; Weeks 10, 14, 18, 22, and 26	Change from baseline was calculated as values at Days 8, 15, 22, 29, 36, and 43 and Weeks 10, 14, 18, 22, and 26 minus baseline value. Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.
Percentage of Participants With a Reduction in Dose and/or Number of Drugs of Concomitant ITP Medications From Baseline	Baseline through Week 26	ITP medications are drugs, such as steroids or immunoglobulin, to be used for ITP. Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.
Mean Number of Days of Concomitant ITP Medication Use Per Month	Weeks 1 through 26	Cumulative number of days for which a participant received ITP medication during the treatment/total treatment period (months). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.
Pharmacokinetics of SB-497115, t1/2	Week 9 or 10	t1/2 is half life based on the terminal phase
Pharmacokinetics of SB-497115-GR, AUClast and AUC0-24	Week 9 or 10	AUC is area under a concentration vs. time curve. AUC0-24 (Area under the plasma concentration-time curve between 0 to 24 hrs) is calculated using the following equation: AUC0-24= AUClast + Clast × (1 - e-λz × \[24-tlast\])/λz. AUClast is AUC (area under a curve) computed to the last observation. Clast is concentration of last observation.
Mean Maximum Duration for Which Participants Maintained Platelet Counts >=50 x 10^9/Liter and <=400 x 10^9/Liter	Weeks 1 through 26	Maximum duration is measured as the longest period (days) for which a participant continuously maintained platelet counts within the target range (\>=50 x 10\^9/Liter and \<=400 x 10\^9/Liter). Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.
Percentage of Participants Who Received Rescue Treatment for ITP	Weeks 1 through 26	Rescue treatment for ITP is treatment applied to participants at high bleeding risk, such as those undergoing platelet transfusion or dose increase of steroids. Participants receiving placebo in the double-blind phase received SB-497115-GR in the open-label phase for up to 26 weeks. Participants receiving SB-497115-GR in the double-blind phase for 7 weeks continued to receive SB-497115-GR in the open-label phase for 19 weeks. The data from these two groups were pooled as a 26 week treatment of SB-497115-GR group and analyzed for the efficacy and safety.
Pharmacokinetics of SB-497115-GR, Vz/F	Week 9 or 10	VZ/F: VZ is the volume of distribution based on the terminal phase, and F is the fraction of dose absorbed.