Eltrombopag Phase III Study In Chinese Chronic ITP Patients
Condition: Purpura, Thrombocytopenic, Idiopathic and Hepatitis C
MeSH terms: Hepatitis C; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic
Intervention: eltrombopag; placebo
Intervention description: TPO-R agonist; placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 155.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: eltrombopag; TPO-R agonist; Chronic ITP; ETB115; Chinese chronic ITP patients

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.
    

Eligibility 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.