Purpura, Thrombocytopenic, Idiopathic and Hepatitis C Clinical Trial
Official title:
A Multicenter, Randomized, Double-Blind and Open-label Phase III Study To Compare The Efficacy And Safety Of Eltrombopag With Placebo In Chinese Chronic ITP Patients
This randomized, double-blind and open-label phase III study aimed to determine the efficacy,
tolerance and safety of eltrombopag in Chinese chronic primary immune thrombocytopenia (ITP)
adult subjects. This study was be conducted in Chinese adult chronic ITP subjects who had not
responded to or had relapsed after previous treatment of ITP, including first line therapy
and /or splenectomy.
The primary objective of this study was to determine the efficacy of oral eltrombopag as a
thrombopoietic agent treating previously treated chronic Chinese ITP patients compared to
placebo. The secondary objective was to assess the safety and tolerability of eltrombopag
when administered for 6 weeks to previously treated adult chronic ITP patients compared with
placebo. In addition, the long-term efficacy and safety of eltrombopag treatment was also
evaluated in the 24-week extension open-label phase after the double-blind phase as one of
other study objectives. If the subject benefited from the eltrombopag treatment based on the
investigator's discretion, the subject could continue on eltrombopag treatment until the
commercial launch of eltrombopag in China. Furthermore, to understand the pharmacokinetics
(PK) profile of eltrombopag and to explore the relationship between the PK and
pharmacodynamics (PD) (platelet response), a PK/PD analysis was embedded in this phase III
study and conducted in the same patient population who participated this phase III study.
This randomized, double-blind and open-label phase III study aimed to determine the efficacy,
tolerance and safety of eltrombopag in Chinese chronic primary immune thrombocytopenia (ITP)
adult subjects. This study was conducted in Chinese adult chronic ITP subjects who had not
responded to or had relapsed after previous treatment for ITP, including first line therapy
and /or splenectomy.
The primary objective of this study was to determine the efficacy of oral eltrombopag as a
thrombopoietic agent treating previously treated chronic Chinese ITP patients compared to
placebo. The secondary objective was to assess the safety and tolerability of eltrombopag
when administered for 6 weeks to previously treated adult chronic ITP patients compared to
placebo. In addition, the long-term efficacy and safety of eltrombopag treatment was also
evaluated in the 24-week extension open-label phase after the double-blind phase as one of
other study objectives. If the subject benefited from the eltrombopag treatment based on the
investigator's discretion, the subject could continue the eltrombopag treatment until the
commercial launch of eltrombopag in China. Furthermore, to understand the pharmacokinetics
(PK) profile of eltrombopag and to explore the relationship between the PK and
pharmacodynamics (PD) (platelet response), a PK/PD analysis was embedded in this phase III
study and conducted in the same patient population who participated this phase III study.
155 eligible subjects were randomized to either eltrombopag or matching placebo treatment in
2:1 ratio in stage 1 (the 8-week double blind stage). Randomization for stage 1 was
stratified by splenectomy status (Yes/No), use of concomitant maintenance ITP therapy
(Yes/No) and baseline platelet count (no more than 15×109/L, or >15×109/L). This study
include 3 stages. The stage 1 was an 8-week double-blind, randomized, placebo-controlled
treatment period. Following completion of Stage 1 and after completing the data cleanup of
the initial 6 weeks, the investigator was be un-blinded to treatment assignment on an
individual subject basis to enable appropriate starting dose selection for stage 2, a 24-week
open-label treatment period. PK sampling and assessments occurred at the Week 2 visit during
stage 2 of the study, when all subjects were receiving eltrombopag. After the completion of
stage 2, subjects could continue the the eltrombopag treatment in stage 3, if he/she
benefited from the continuous eltrombopag treatment based on the investigator's judgement.
The initial dose of eltrombopag administration was an oral 25 mg once daily. During the 8
weeks double-blind treatment, dose of investigational product was adjusted according to the
weekly subject platelet count.
The eligible subjects who completed stage 1 (8 weeks of double-blind treatment period: the
first 6 weeks data was used for primary endpoint analysis and the last 2 weeks for data
cleanup period during which the blinded treatment continued) entered a voluntary open-label
stage 2 (24-week open-label extension phase) in which subjects from both the eltrombopag
group and placebo group had the opportunity to receive eltrombopag treatment. Subjects
unwilling or unqualified (such as the subjects who met the stopping criteria) to participate
in extension treatment attended follow-up visits for 4 weeks after the completion of the
double-blind phase. During the open-label stage 2 phase all eligible subjects received open
label eltrombopag treatment. The dose of eltrombopag was continuously adjusted according to
the subject's platelet count.
Following completion of Stage 2, if the subject benefited from the eltrombopag treatment
based on the investigator's discretion, the subject could voluntarily enter stage 3, during
which the subject continued eltrombopag treatment until the commercial launch of eltrombopag
in C
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