Safety and Efficacy of Eltrombopag at Escalated Doses

• Status: Completed
• Trial end date: 2017-10-16
• Target enrollment: 0
• Participant gender: All

Summary

Study rationale is based on the data that in previous clinical studies of eltrombopag in ITP there are some patients who have been reported as non responders at the maximal approved dose of 75 mg daily. The trend in both normal volunteers and in patients with ITP suggest and increasing response rate with increased doses of eltrombopag up to a dose of 75mg. Previously published data has shown no overt increase in toxicity in normal volunteers, oncology patients and aplastic anemia patients treated with escalated doses as high or higher than those proposed in this study.

It therefore seems possible that in ITP patients who did not respond to a dose of 75mg daily, eltrombopag could be more effective at a higher dose. We propose a double blind randomized controlled trial in ITP patients who have been defined as non-responders at the maximum dose (75mg) of eltrombopag, assessing efficacy and toxicity at higher daily doses (100mg, 125 mg, 150 mg)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Weill Medical College of Cornell University
• Collaborators: GlaxoSmithKline; Novartis

Criteria

Inclusion Criteria:

• Subject or their parent/ guardian has signed and dated a written informed consent

• Male and Females aged 12 years or older diagnosed with chronic ITP according to the new consensus guidelines

• No indication of a disease which may cause thrombocytopenia other than ITP----no specific testing required

• Subjects with thrombocytopenia ≤ 50,000 /uL after at least 21 days of daily dosage with eltrombopag 75mg

• Stable dosage of concomitant treatments for ITP

≥ 2 weeks or longer (corticosteroids);

• At least 2 weeks from rescue therapy for ITP (WinRho, Intravenous Immunoglobulin (IVIG), corticosteroids, platelet transfusion)

• At least 4 weeks from rituximab treatment

• Pregnant or Lactating Women are excluded

• Women of child-bearing age with a negative pregnancy test within 7 days of enrollment and who agree to use acceptable methods of birth control will be eligible for this study

• Female subjects or female partners of male subjects must either be of non-child bearing potential (hysterectomy, bilateral ovariectomy, bilateral tubal ligation or post menopausal for more than one year) OR, if of child bearing potential, using one of the following highly effective methods of contraception.

• complete abstinence from intercourse

• Intrauterine device (IUD)

• Two forms of barrier contraception. diaphragm plus spermicide, or for males condoms plus spermicide.

• Male partner is sterile and is the only partner of the female.

• Systemic contraceptives (combined oral progesterone only)

Exclusion Criteria:

• Previous history of eltrombopag-related liver function test (LFT) elevation that required interruption of treatment

• Previous history of immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag

• HIV Infection

• History of Arterial of Venous Thrombosis within the past year or requiring ongoing therapy

• Active Hepatitis C infection

• Treatment with medications that affect platelet function ( including but not limited to Aspirin, Clopidogrel and /or NSAIDs) or anti-coagulant medications

• Elevated Aspartate Aminotransferase(AST/ALT) or Creatinine > 1.5 times upper limit of normal in 4 weeks prior to enrollment*

• Abnormalities in white blood cell count (WBC), automatic neutrophil count (ANC), and Hemoglobin > 1.5 times upper or lower limit of normal*

• * Subjects can be rescreened to be included