Oral LGD-4665 Versus Placebo in Adults With Immune Thrombocytopenic Purpura (ITP) for 6 Weeks Plus Open Treatment Continuation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00621894
First received: February 12, 2008
Last updated: July 26, 2012
Last verified: August 2011
  Purpose

The purpose of this study is to assess the ability of LGD-4665 given daily by mouth to increase platelet counts in the treatment of patients with ITP (immune thrombocytopenic purpura). LGD-4665 increased platelet counts safely and tolerably compared to placebo in healthy volunteers. This study will examine the safety, tolerability and efficacy of 7.5 mg capsules of LGD-4665 to increase platelets compared to placebo, randomized 2:1, during blinded treatment for 6 weeks. Evaluation of platelet counts, bleeding scores and safety parameters will be done weekly. All patients are eligible to continue on active, open LGD-4665 treatment for an additional 12 weeks with optimal adjustment of dose for each patient.


Condition Intervention Phase
Immune Thrombocytopenic Purpura
Drug: LGD-4665
Drug: Placebo
Phase 2

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: A Phase IIA Randomized, Double-Blind, Placebo-Controlled Study of LGD-4665 in Patients With Immune Thrombocytopenic Purpura (ITP) With an Open Label Extension

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Platelet counts [ Time Frame: Week 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bleeding score [ Time Frame: Weeks 1 - 20 ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: March 2008
Study Completion Date: May 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
LGD-4665: Experimental Thrombopoietin mimetic
Drug: LGD-4665
LGD-4665 Thrombopoietin mimetic
Placebo Comparator: 2 Drug: Placebo
Placebo

Detailed Description:

This is a Phase IIA study with two parts to the design.

  • Part 1 is a randomized, double-blinded, placebo-controlled treatment of 7.5 mg/day LGD-4665 versus placebo in approximately 24 patients with ITP who have been treated with at least one prior therapy for ITP. Patients will be randomized in a ratio of 1:2 (placebo: 7.5 mg/day LGD-4665) for 6 weeks of treatment. Platelet counts, bleeding scores, vital signs, physical exams and laboratory tests will be assessed weekly. Treatment groups will be analyzed for efficacy by the percentage of patients with platelet counts two times baseline and ≥ 50,000/uL at 6 weeks of treatment, and for safety by adverse events, vital signs, physical exams, laboratory tests and use of ITP rescue medications or transfusions.
  • Part 2 is an extension of study treatment with open label LGD-4665. All patients who participate in the Part 1 randomized double-blind treatment of this Ph IIA trial are eligible to continue open label treatment with LGD-4665 for up to 3 months at an appropriate dose for the safe maintenance of platelet counts (≥ 50,000/uL to ≤ 200,000/uL). Assessments of effectiveness and safety will be made at 2 and 4 week intervals.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults 18 years or older
  • Diagnosis of ITP for at least 3 months consistent with ASH guidelines
  • Treated with one or more prior therapies for ITP and platelet counts < 30,000/µL or < 50,000/µL if on a stable oral corticosteroid for ≥ 4 weeks, supported by 2 platelet counts in prior 30 days
  • Laboratory results within normal range except for the following analytes

    • Hemoglobin ≥ 10 g/dL
    • Absolute neutrophil counts > 1000/mL
    • ALT ≤ 1.5X ULN
    • AST ≤ 1.5X ULN
    • Creatinine < 1.5X ULN
    • Bilirubin < 1.5X ULN
    • BUN < 1.5X ULN
    • PT < 1.5X ULN
    • aPTT <1.5X ULN
  • Women of child-bearing potential must have a negative serum pregnancy test within 4 days prior to the first dose of study treatment and agree to practice an approved method of contraception or abstinence from sexual intercourse.
  • Willing to sign a written informed consent

Exclusion criteria:

  • History of heart attack or cardiovascular disease
  • Known history of arterial or venous thrombosis
  • More than 3 risk factors for thromboembolic events (diabetes, smoker, using oral contraception, using estrogen therapy, hypertriglyceridemia, average cholesterol > 240 mg/dL, treatment for hypertension)
  • Active cancer or a history of bone marrow disorders
  • Women who are pregnant or nursing
  • History of alcohol/drug abuse or dependence within one year
  • Listed medications dosed within:

    • 4 weeks of the first dose of the study treatment:

      • Use of Rituximab
      • Use of cytotoxic agents
      • Use of Cyclosporine and other immunomodulators
      • Use of an investigational drug
    • 2 weeks of the first dose of the study treatment:

      • Use of Danazol
      • Use of Azathioprine
      • Use of Mycophenolate mofetil and pulsed-dose steroids
    • 1 week of the first dose of the study treatment:

      • Use of Anti-D (WinRho®)
      • Use of IVIG
      • Had a platelet transfusion
      • Use of herbal/dietary supplements (excluding vitamins and mineral supplements)
    • 3 days of the first dose of the study treatment

      • Use of aspirin, aspirin containing compounds
      • salicylates
      • milk of magnesia
      • non-steroidal anti-inflammatory drugs (unless prescribed for heart disease)
  • History of platelet aggregation that would prevent measurement of platelet counts
  • Known active infection with HIV, hepatitis B, or hepatitis C
  • In the Investigator's opinion, the patient is not able to comply with requirements of the study
  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: NCT00621894

Locations
United States, California
University of California San Diego Medical Center
San Diego, California, United States, 92103-8409
University of California, San Francisco
San Francisco, California, United States, 94143-1270
United States, Connecticut
Davis, Posteraro and Wasser, MD's LLP
Manchester, Connecticut, United States, 06040
United States, Florida
Baptist Cancer Institute
Jacksonville, Florida, United States, 32207
Cancer Center of Florida
Orlando, Florida, United States, 32806
United States, Georgia
Georgia Cancer Specialists
Atlanta, Georgia, United States, 30341
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
Karmanos Cancer Center, Wertz Clinical Cancer Center 4HWCRC
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University School of Medicine - St Louis, MO
St. Louis, Missouri, United States, 63110
United States, New Mexico
New Mexico Oncology Hematology Consultants
Albuquerque, New Mexico, United States, 87109
United States, New York
Joan and Sanford I. Weill Medical College, Cornell University
New York, New York, United States, 10021
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Ohio
Cleveland Clinic Foundation, Univ. of Ohio
Cleveland, Ohio, United States, 44195
Case Western Reserve University School of Medicine
Cleveland, Ohio, United States, 44106-7284
United States, Texas
Hematology Oncology Associates of South Texas
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00621894     History of Changes
Other Study ID Numbers: L4665-03
Study First Received: February 12, 2008
Last Updated: July 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Immune thrombocytopenic purpura
thrombopoietin mimetic
ITP

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases

ClinicalTrials.gov processed this record on July 28, 2014