Safety and Efficacy of Eltrombopag at Escalated Doses

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Weill Medical College of Cornell University
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT01880047
First received: November 20, 2012
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

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)


Condition Intervention Phase
Immune Thrombocytopenia
Platelet Disorder
Drug: Eltrombopag
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Eltrombopag at Escalated Doses up to 150mg in Patients With Persistent and Chronic Immune Thrombocytopenia (ITP) Not Responsive to 75 mg

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Proportion of patients responding to >75mg daily [ Time Frame: Evaluated throughout the study. Endpoints will be at 8 weeks of the blinded study and in the open label portion of the study up to 18 months. ] [ Designated as safety issue: No ]
    To determine the proportion of patients with chronic ITP who do not respond to 75 mg of eltrombopag daily given for at least 3 weeks but then do respond to eltrombopag given daily first for 2 weeks at doses of 100, then for 2 weeks at 125 mg and finally for 4 weeks at a dose of 150mg daily. Dosing will stop if the platelet count exceeds 100,000. Response will be defined as 2 consecutive platelet counts of > 50,000 and an increase of > 20,000 from the study baseline within the 8 week increased dose window not as a result of rescue treatment.


Secondary Outcome Measures:
  • Efficacy of increased dosage of eltrombopag in ITP patients at doses > 75 [ Time Frame: Evaluated throughout the study. Endpoints will be at 8 weeks of the blinded study and in the open label portion of the study up to 18 months. ] [ Designated as safety issue: No ]
    To determine efficacy of administration of increased dosage of eltrombopag to subjects with chronic ITP who did not respond to current maximally approved daily dose of 75 mg for at least 3 weeks by measuring: number of weeks of platelet counts of response; number of durable responses here defined as platelet counts of response for 3 weeks among the last 4 weeks; number of patients achieving a platelet count > 100,000 and number of platelet counts per patient > 100,000. (Note if a platelet count > 150,000 is achieved that week and the subsequent weeks of the 8 week study will be considered to all be over 100,000 for purposes of all analyses).


Other Outcome Measures:
  • Evaluating safety in patients receiving doses > 75mg [ Time Frame: up to 18 months. ] [ Designated as safety issue: Yes ]

    To determine the safety of administration of increased dosage of eltrombopag to subjects with ITP who did not respond to current maximally approved daily dose of 75 mg for at least 3 weeks.

    To evaluate if there are subgroups of patients (despite being underpowered) who are more likely or less likely to either respond or to experience adverse events:Starting platelet counts, splenectomy status, concomitant meds e.g, daily prednisone at a maximum dose of 20mg daily, duration of ITP diagnosis, starting Hemoglobin and Absolute Neutrophil Count (ANC), starting ALTs, bilirubins or Alk Phos levels, Platelet Reticulocyte Count



Estimated Enrollment: 36
Study Start Date: February 2013
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Eltrombopag
Subjects in the study will receive 75 mg eltrombopag and then be randomized to receive either an additional 25 mg of eltrombopag or matching placebo tablet dispensed by the research pharmacy. Subjects and investigators will be blinded to randomization. Randomization will be stratified according to splenectomy status. Randomization will be performed at the time of informed consent with a computer generated randomization table. Subjects and investigators will be blinded to assignment and treatment in this phase.
Drug: Eltrombopag
Eltrombopag will be administered for 8 weeks or until the platelet count exceeds 150,000; at this point dosing will stop, subject will be considered a responder and the subject will eligible for entering Part 2 (the long term treatment part of the study. The dose at which the subject achieved the primary endpoint (> 50,000 and increase by > 20,000) will be considered the dose of response. Dose escalation will continue, despite satisfaction of the primary endpoint of study (> 50,000 and > 20,000 above baseline), unless the platelet count reaches the lower limit of normal range 150,000. Subjects will stop study medication if the platelet count is within the normal range, thereby minimizing any safety risk associated with elevated platelet count.
Other Names:
  • Eltrombopag
  • SB-497115
  • Promacta
Placebo Comparator: Placebo
Subjects will be randomly allocated in a two to one ratio to receive treatment or placebo. All subjects in the study will receive 75 mg eltrombopag and then be randomized to receive either an additional 25 mg of eltrombopag or matching placebo tablet dispensed by the research pharmacy. Subjects and investigators will be blinded to randomization. Randomization will be stratified according to splenectomy status.
Drug: Placebo

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  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ( Provan, Blood, 2009)
  • 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, 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 GSK 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 ovarectomy, bilateral tubal ligation or post menauposal 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 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 AST/ALT or Creatinine > 1.5 times upper limit of normal in 4 weeks prior to enrollment*
  • Abnormalities in WBC, ANC and Hemoglobin > 1.5 times upper or lower limit of normal*
  • * Subjects can be rescreened to be included
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01880047

Contacts
Contact: James B Bussel, M.D. 212.746.3474 jbussel@med.cornell.edu

Locations
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Contact: James B Bussel, M.D.    212-746-3474    Jbussel@med.cornell.edu   
Principal Investigator: James B Bussel, M.D.         
Sub-Investigator: Catherine McGuinn, M.D.         
Sponsors and Collaborators
Weill Medical College of Cornell University
GlaxoSmithKline
Investigators
Principal Investigator: James B Bussel, M.D. Weill Medical College of Cornell University
Principal Investigator: Catherine McGuinn, M.D. Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01880047     History of Changes
Other Study ID Numbers: 116862
Study First Received: November 20, 2012
Last Updated: June 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
Immune Thrombocytopenia
ITP
Eltrombopag
Promacta

Additional relevant MeSH terms:
Blood Platelet Disorders
Thrombocytopenia
Hematologic Diseases

ClinicalTrials.gov processed this record on July 22, 2014