Phase 3
Completed N=302
EXTEND (Eltrombopag Extended Dosing Study)
Purpura, Thrombocytopaenic, Idiopathic
Source: ClinicalTrials.gov NCT00351468 ↗
Enrolled (actual)
302
Serious AEs
17.5%
Results posted
Apr 2017
Primary outcomePrimary: Overall Summary of On-Therapy Adverse Events (Safety Population) — 277; 96; 133; 41 Participants
◆ Published Evidence
Highly cited
336citations · ~26 / year
Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study.
Summary
An open-label, dose-adjustment, extension study to evaluate the safety and efficacy of eltrombopag for the treatment of subjects with idiopathic thrombocytopenic purpura (ITP) who have previously been enrolled in an eltrombopag trial. This study will allow adjustment of the eltrombopag dose to achieve an individualized dose and schedule for each subject. In addition, the ability to reduce the dose of concomitant ITP medications in the presence of eltrombopag, while maintaining platelet counts = 50,000/μL will be investigated.
Linked Publications (5)
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Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study.
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Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study.
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Selective validation of the WHO Bleeding Scale in patients with chronic immune thrombocytopenia.
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Validation of the FACIT-fatigue subscale, selected items from FACT-thrombocytopenia, and the SF-36v2 in patients with chronic immune thrombocytopenia.
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Efficacy of eltrombopag in management of bleeding symptoms associated with chronic immune thrombocytopenia.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Summary of On-Therapy Adverse Events (Safety Population) |
277; 96; 133; 41; 28 | — |
| SECONDARY Subjects Achieving Maximum Platelet Counts Greater Than or Equal to 30 Gi/L or 50 Gi/L in the Absence of Rescue Medication |
91; 42; 276; 259 | — |
| SECONDARY Summary of Subjects Achieving Platelet Count Levels by Week, in the Absence of Rescue Medication |
91; 42; 172; 127; 199; 165 | — |
| SECONDARY Number of Subjects Who Responded to Eltrombopag in a Previous Study and Who Respond to Retreatment With a Rise in Platelet Count to Either ≥ 50,000/µL or ≥30,000/µL |
49; 47; 49; 54; 53; 55 | — |
| SECONDARY Number of Participants With Reduction and/or Sparing of Concomitant ITP Therapies, While Maintaining a Platelet Count ≥ 50,000/mL. |
101; 71; 53; 70; 66 | — |
| SECONDARY Number of Subjects Who Required Rescue Therapy During Treatment With Eltrombopag. |
82; 27; 21; 3 | — |
| SECONDARY Maximum ITP Bleeding Score at Any Time During the Study During All Stages. |
204; 65; 31; 264; 26; 10 | — |
| SECONDARY Best Post-Baseline Change in SF-36v2 Questionnaire Score From Any Time Point Compared With Baseline |
12.0; 14.2; 14.5; 11.1; 13.9; 12.6 | — |
| SECONDARY Best Post-Baseline Change in the Short Form of the Motivation and Energy Scale (MEI-SF) From Any Time Point Compared With Baseline |
11.3 | — |
| SECONDARY Best Post-Baseline Change in the FACIT-Fatigue 13 Item Subscale Score From Any Time Point Compared to Baseline |
6.9 | — |
| SECONDARY Best Post-Baseline Change in the FACT-TH6 at Any Time Point Compared to Baseline |
4.0 | — |
Eligibility Criteria
Inclusion Criteria
- Subject has signed and dated a written informed consent.
- Adults (≥18 years) diagnosed with ITP according to the American Society for Hematology/British Committee for Standards in Haematology (ASH/BCSH) guidelines [George, 1996; BCSH, 2003]. In addition, a peripheral blood smear should support the diagnosis of ITP with no evidence of other disease causative of thrombocytopenia (e.g., pseudo thrombocytopenia, myelofibrosis). The physical examination should not suggest any disease which may cause thrombocytopenia other than ITP.
- Prior completion of treatment and follow up periods in an ITP study of eltrombopag (e.g., TRA100773 or TRA102537/RAISE or TRA108057/REPEAT).
- Subjects previously enrolled in Study TRA100773 must have completed the prescribed follow-up ophthalmic assessment at 6 months.
- Subjects previously enrolled in TRA102537/RAISE or other studies that may lead into EXTEND (e.g., TRA108057/REPEAT) must have completed the treatment and follow-up periods as defined in that protocol.
- Subject experienced no eltrombopag-related toxicity or other drug intolerance on prior eltrombopag study (e.g., TRA100773 or TRA102537/RAISE or TRA108057/REPEAT) even if resolved; subjects discontinued from previous study due to toxicity will not be eligible unless they received placebo.
- Subject has no intercurrent medical event, including thrombosis.
- Subjects must have either initially responded (platelet count > 100,000/mL) to a previous ITP therapy or have had a bone marrow examination consistent with ITP within 3 years to rule out myelodysplastic syndromes or other causes of thrombocytopenia
- Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have been completed at least 1 week prior to first dose of study medication and the platelet count must show a clear downward trend after the last treatment with immunoglobulins. Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been completed at least 4 weeks prior to randomization, or clearly be ineffective.
- Subjects treated with concomitant ITP medication (e.g. corticosteroids or azathioprine) must be receiving a dose that has been stable for at least 4 weeks prior to randomization. Subjects treated with cyclosporine A, mycophenolate mofetil or danazol must be receiving a dose that has been stable for at least 3 months prior to the first dose of study medication.
- Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must be within 80 to 120% of the normal range with no history of hypercoagulable state.
- A complete blood count (CBC), within the reference range (including WBC differential not indicative of a disorder other than ITP), with the following exceptions:
- Hemoglobin: Subjects with hemoglobin levels between 10.0 g/dL and the lower limit of normal are eligible for inclusion, if anemia is clearly attributable to ITP (excessive blood loss).
- ANC≥1500/mL (1.5 x 10^9/L) is required for inclusion (elevated WBC/ANC due to steroid treatment is acceptable).
- The following clinical chemistries MUST NOT exceed the upper limit of normal (ULN) reference range by more than 20%: creatinine, ALT, AST, total bilirubin, and alkaline phosphatase. In addition, total albumin must not be below the lower limit of normal (LLN) by more than 10%.
- Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use one of the following highly effective methods of contraception (i.e., Pearl Index 450 msec.
- Female subjects who are nursing or pregnant (positive serum or urine b-human chorionic gonadotrophin (b-hCG) pregnancy test) at screening or pre-dose on Day 1.
- History of alcohol/drug abuse.
- Treatment with an investigational drug within 30 days or five
Data sourced from ClinicalTrials.gov (NCT00351468) and the linked publication. 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.