Phase 3
Completed N=155
Eltrombopag Phase III Study In Chinese Chronic ITP Patients
Purpura, Thrombocytopenic, Idiopathic and Hepatitis C
Source: ClinicalTrials.gov NCT01762761 ↗
Enrolled (actual)
155
Serious AEs
32.3%
Results posted
Mar 2015
Primary outcomePrimary: Number of Participants (Responders) Achieving a Platelet Count >=50×10^9/L After the First 6 Weeks of Stage 1 — 3; 60 Participants — p=<0.001
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants (Responders) Achieving a Platelet Count >=50×10^9/L After the First 6 Weeks of Stage 1 |
3; 60 | <0.001 sig |
| SECONDARY Number of Participants Achieving a Platelet Count >=50×10^9/L at Least Once During the First 6 Weeks of Stage 1 |
9; 80 | <0.001 sig |
| SECONDARY 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, the Whole Stage 2 and the Whole Stage 3 |
18; 84; 45; 81; 36; 72 | <0.001 sig |
| SECONDARY Number of Participants With Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale |
36; 68; 30; 43; 27; 32 | 0.001 sig |
| SECONDARY Number of Participants With Clinically Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale |
5; 14; 5; 12; 4; 13 | 0.306 |
| SECONDARY Time to Response |
NA; 3.14 | <0.001 sig |
| SECONDARY Number of Participants Who Required Protocol-defined Rescue Treatment During the First 6 Weeks of Stage 1, Whole Stages 2 & 3 |
17; 9; 16; 14; 13; 21 | <0.001 sig |
| SECONDARY Number of Participants With a Platelet Count >=50×10^9/L During at Least 75% of Their Platelet Count Assessments |
1; 23; 10; 38; 13; 30 | 0.008 sig |
| SECONDARY Total Duration of Time a Participant Had a Platelet Count >=50×10^9/L |
0.00; 1.79; 4.07; 7.29; 27.00; 43.71 | <0.001 sig |
| SECONDARY Maximum Period of Time a Participant Had a Platelet Count Continuously >= 50 ×10^9/L |
0.00; 1.57; 2.71; 5.00; 16.43; 28.14 | <0.001 sig |
| SECONDARY Number of Participants That Reduced or Discontinued Baseline Concomitant ITP Medications During Stage 2 and Stage 3 |
19; 20; 5; 16 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) |
34; 66; 5; 5; 43; 64 | — |
| SECONDARY Number of Participants With the Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters |
8; 10; 0; 2; 0; 0 | — |
| SECONDARY Number of Participants With the Maximum Toxicity Grade for the Indicated Hematology Parameters |
21; 35; 1; 11; 3; 4 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure |
-0.3; -0.7; -2.0; -0.2; 0.3; -1.5 | — |
| SECONDARY Change From Baseline in Diastolic Blood Pressure |
-0.3; -0.5; -1.1; -0.1; -1.0; -1.5 | — |
| SECONDARY Change From Baseline in Pulse Rate |
-0.5; 0.2; -2.2; 0.2; 1.6; 0.2 | — |
| SECONDARY Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Finding at Baseline |
36; 57; 14; 43; 0; 4 | — |
| SECONDARY Number of Participants With a Change From Baseline in Visual Acuity |
24; 33; 22; 35 | — |
| SECONDARY Number of Participants With the Indicated Grading of Myelofibrosis Using Bone Marrow Biopsy at Screening |
38; 83; 13; 19; 0; 0 | — |
| SECONDARY Pharmacokinetic (PK) Assessments for Eltrombopag for Apparent Volume of Distribution of Central Compartment (Vc/F), Apparent Volume of Distribution of Peripheral Compartment (Vp/F) |
8.80; 33.6 | — |
| SECONDARY Pharmacokinetic Assessments for Eltrombopag for Apparent Clearance (CL/F), Apparent Inter-compartmental Clearance (Q/F) |
0.370; 0.561 | — |
| SECONDARY Pharmacokinetic Assessments for Eltrombopag for Absorption Rate Constant (Ka) |
1.58 | — |
| SECONDARY Pharmacokinetic Assessments for Eltrombopag for Absorption Lag Time (ALAG) |
0.855 | — |
| SECONDARY 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 |
88.8 | — |
| SECONDARY Post-hoc Estimates of Maximum Observed Concentration (Cmax) for Eltrombopag After 50 mg Once Daily Dose of Eltrombopag |
6916 | — |
| SECONDARY Percentage of Participants Estimated as Responders to Eltrombopag by the Pharmacokinetic/ Pharmacodynamic Model |
89 | — |
| SECONDARY 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 |
0.860 | — |
| SECONDARY Pharmacodynamic Parameter- Production Rate of Platelet Precursors (KIN) |
1.43 | — |
| SECONDARY Pharmacodynamic Parameter-Maturation Rate of Platelet Precursors (KOUT) |
0.0253 | — |
Eligibility Criteria
Inclusion Criteria
- Subject is ≥18 years old.
- Diagnosed with ITP for at least 12 months prior to screening, and have a platelet count of 450msec or QTc >480 for patients with a Bundle Branch Block.
- No history of clotting disorder, other than ITP.
- A complete blood count (CBC), within the reference range, with the following exceptions:
- Platelets 3 consecutive days within 2 weeks of the study start and until the end of the study.
- Consumption of any herbal or dietary supplements, excluding vitamin or mineral supplements, within 1 week of the study start.
- History of platelet aggregation that prevents reliable measurement of platelet counts.
- 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).
- Any laboratory or clinical evidence for HIV infection.
- 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.
- Patients expected to require rescue on Day 1 of the study.
Data sourced from ClinicalTrials.gov (NCT01762761). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.