Last updated: 11/03/2018 15:36:21
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
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
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
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
Trial description: This randomized, double-blind and open-label phase III study is aimed to determine the efficacy, tolerance and safety of eltrombopag in Chinese chronic primary immune thrombocytopenia (ITP) adult subjects. This study will be conducted in Chinese adult chronic ITP subjects who have not responded to or have relapsed after previous treatment for ITP, including first line therapy and /or splenectomy.The primary objective of this study is to determine the efficacy of oral eltrombopag as a thrombopoietic agent treating previously treated chronic Chinese ITP patients comparing with placebo. The secondary objective is to assess the safety and tolerability of eltrombopag when administered for 6 weeks to previously treated adult chronic ITP patients comparing with the placebo. In addition, the long-term efficacy and safety of eltrombopag treatment will be also evaluated in the 24-week extension open-label phase after the double-blind phase as one of other study objectives. If the subject benefits from the eltrombopag treatment based on investigator’s discretion, the subject can continue 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 will be embedded in this phase III study and conducted in the same patient population participated this phase III study.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Number of participants (responders) achieving a platelet count >=50×10^9/L after the first 6 weeks of Stage 1
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Secondary outcomes:
Number of participants with a platelet count >=50×10^9/L during at least 75% of their platelet count assessments
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Number of participants with the maximum toxicity grade for the indicated clinical chemistry parameters
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Pharmacokinetic Assessments for Eltrombopag for absorption rate constant (Ka)
Timeframe: From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Pharmacodynamic parameter-Maturation Rate of Platelet Precursors (KOUT)
Timeframe: From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Post-hoc estimates of maximum observed concentration (Cmax) for Eltrombopag after 50 mg once daily dose of eltrombopag
Timeframe: From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Pharmacodynamic parameter- Production Rate of Platelet Precursors (KIN)
Timeframe: From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Number of participants with clinically significant bleeding as assessed using the World Health Organization (WHO) Bleeding Scale
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Number of participants with bleeding as assessed using the World Health Organization (WHO) Bleeding Scale
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Number of participants that reduced or discontinued Baseline concomitant ITP medications during Stage 2 and Stage 3
Timeframe: From the start of Week 1 of Stage 2 to the end of last week of Stage 3
Number of participants with the maximum toxicity grade for the indicated hematology parameters
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Change from Baseline in pulse rate
Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6
Pharmacokinetic (PK) Assessments for Eltrombopag for apparent volume of distribution of central compartment (Vc/F), apparent volume of distribution of peripheral compartment (Vp/F)
Timeframe: From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Number of participants with the indicated grading of myelofibrosis using bone marrow biopsy at Screening
Timeframe: Screening
Change from Baseline in systolic blood pressure
Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6
Maximum period of time a participant had a platelet count continuously >= 50 ×10^9/L
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Number of participants with any adverse event (AE) or serious adverse event (SAE)
Timeframe: From the start of study treatment (Day 1) up to the end of Week 8 of Stage 1
Number of participants achieving a platelet count >=30×10^9/L and at least 2 times the Baseline platelet count at least once during the 6 weeks of Stage 1
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Number of participants with a change from Baseline in visual acuity
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Pharmacokinetic Assessments for Eltrombopag for absorption lag time (ALAG)
Timeframe: From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Number of participants who required protocol-defined rescue treatment during the first 6 weeks of Stage 1
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Time to response
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Pharmacodynamic parameter-Linear Proportionality Constant of Drug Effect (SLOP): the proportional increase of platelet production rate with each 1-μg/mL increase in eltrombopag plasma concentration
Timeframe: From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Post-hoc estimates of plasma eltrombopag area under the concentration-time curve over a dosing interval (AUC[0-tau]) after 50 mg once daily dose of eltrombopag
Timeframe: From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Change from Baseline in diastolic blood pressure
Timeframe: Baseline, Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6
Total duration of time a participant had a platelet count >=50×10^9/L
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Number of participants achieving a platelet count >=50×10^9/L at least once during the first 6 weeks of Stage 1
Timeframe: From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1
Percentage of participants estimated as responders to eltrombopag by the Pharmacokinetic/ Pharmacodynamic model
Timeframe: From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Pharmacokinetic Assessments for Eltrombopag for apparent clearance (CL/F), apparent inter-compartmental clearance (Q/F)
Timeframe: From the start of study until 24 hours post-dose of Week 2 Visit of Stage 2
Number of participants with the indicated 12-lead Electrocardiogram (ECG) finding at Baseline
Timeframe: Baseline
Interventions:
Enrollment:
155
Primary completion date:
2014-05-06
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Purpura, Thrombocytopenic, Idiopathic and Hepatitis C
Product
eltrombopag
Collaborators
Not applicable
Study date(s)
February 2013 to July 2017
Type
Interventional
Phase
2/3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
none
- 1.Subject is ≥18 years old.
- 2.Diagnosed with ITP for at least 12 months prior to screening, and have a platelet count of <30 X109/L on Day 1 (or within 48 hours prior to dosing on Day 1).
- 1.Patients with any prior history of arterial or venous thrombosis, 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, ATIII deficiency, antiphospholipid syndrome, etc).
- 2.Any clinically relevant abnormality, other than ITP,which in the opinion of the investigator makes the subject unsuitable for participation in the study.
Inclusion and exclusion criteria
Inclusion criteria:
- 1.Subject is ≥18 years old. 2.Diagnosed with ITP for at least 12 months prior to screening, and have a platelet count of <30 X109/L on Day 1 (or within 48 hours prior to dosing on Day 1). 3.Patients who have no response or relapsed after splenectomy. Or patients who have not been splenectomised and have either not responded to one or more prior therapies (except splenectomy), or who have relapsed prior therapy. 4.Previous therapy for ITP including rescue must have been completed at least 2 weeks prior to randomization. 5.Subjects treated with maintenance immunosuppressive therapy must be receiving a dose that has been stable for at least 1 month. 6.No pre-existing cardiac disease within the last 3 months. No arrhythmia known to increase the risk of thrombolic events (e.g. atrial fibrillation), or patients with a Corrected QT interval (QTc) >450msec or QTc >480 for patients with a Bundle Branch Block. 7.No history of clotting disorder, other than ITP. 8.A complete blood count (CBC), within the reference range, with the following exceptions: –Platelets <30×109/L on Day 1 (or within 48hours of Day 1) is required for inclusion, –Hemoglobin: females and males 10.0 g/dl are eligible for inclusion, –Absolute neutrophil count (ANC) ≥1500/µL (1.5×109/L) is required for inclusion 9.Blood chemistry test result no exceed normal by more than 20%. Total albumin must not be below the lower limit of normal (LLN) by more than 10%. 10.Subject is non-childbearing potential of childbearing potential and use 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.
Exclusion criteria:
- 1.Patients with any prior history of arterial or venous thrombosis, 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, ATIII deficiency, antiphospholipid syndrome, etc). 2.Any clinically relevant abnormality, other than ITP,which in the opinion of the investigator makes the subject unsuitable for participation in the study. 3.Female subjects who are nursing or pregnant at screening or pre-dose on Day 1. 4.History of alcohol/drug abuse or dependence within 12 months of the study. 5.Treatment with thrombopoietin or an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication. 6.Subjects who have previously received eltrombopag or any other thrombopoietin receptor agonist. 7.Subject has consumed aspirin, aspirin-containing compounds, salicylates, anticoagulants, quinine or non-steroidal anti-inflammatories (NSAIDs) for >3 consecutive days within 2 weeks of the study start and until the end of the study. 8.Consumption of any herbal or dietary supplements, excluding vitamin or mineral supplements, within 1 week of the study start. 9.History of platelet aggregation that prevents reliable measurement of platelet counts. 10. An abnormality in bone marrow examination result, other than ITP, identified on the screening examination, which in the opinion of the investigator makes the subject unsuitable for participation in the study (e.g. ≥MF-2 according to EU consensus scale [Thiele, 2005]) or suggests another primary diagnosis (e.g. Thrombocytopenia is secondary to another disease). 11. Any laboratory or clinical evidence for HIV infection. 12. Any clinical history for hepatitis C infection; chronic hepatitis B infection; or any evidence for active hepatitis at the time of subject screening. Laboratory test shows positive serology for Hepatitis C or Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. 13. Patients expected to require rescue on Day 1 of the study.
Trial location(s)
This study does not involve prospective enrollment of participants.
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
No longer a GSK study
Actual primary completion date
2014-05-06
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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