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Study of AKR-501 Tablets Taken Orally Once Daily for 28 Days in Patients With Chronic Idiopathic Thrombocytopenic Purpura (ITP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00441090
First received: February 27, 2007
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to determine the efficacy, safety and tolerability, of AKR-501 tablets, as compared to placebo, in the treatment of patients with chronic Idiopathic Thrombocytopenic Purpura (ITP).


Condition Intervention Phase
Chronic Idiopathic Thrombocytopenic Purpura
Purpura, Thrombocytopenic, Idiopathic
Drug: Placebo
Drug: AKR-501 Tablets
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Double-Blind, Randomized, Dose-Ranging, Placebo-Controlled, Parallel Group Study of AKR-501 Tablets Taken Orally Once Daily for 28 Days in Patients With Chronic Idiopathic Thrombocytopenic Purpura (ITP).

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Assess response to therapy on Day 28 [ Time Frame: Days 3, 5, 7, 14, 21, 28 and 42 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the pharmacokinetics (PK) and the pharmacokinetic/pharmacodynamic (PK/PD) relationship of AKR-501 in patients with ITP. [ Time Frame: Days 7, 14, 21 and 28 ] [ Designated as safety issue: No ]

Enrollment: 64
Study Start Date: February 2007
Study Completion Date: June 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AKR-501 Tablets

2.5, 5, 10 or 20 mg tablets

1 tablet taken orally once daily for 28 days

Drug: AKR-501 Tablets
AKR-501 Tablets 2.5, 5, 10 and 20 mg taken orally once daily for 28 days.
Placebo Comparator: Placebo tablet

2.5, 5, 10, or 20 mg tablets

1 tablet taken orally once daily for 28 days

Drug: Placebo
Placebo Tablets 2.5, 5, 10 and 20 mg taken orally once daily for 28 days.

Detailed Description:

This is a Phase 2, multi-center, double-blind, randomized, placebo-controlled, dose-ranging, parallel-group study. The PK and PK/PD relationship of AKR-501 will also be studied. Approximately 65 eligible patients will be randomized in a 3:3:3:3:1 ratio in a double-blinded fashion into one of five parallel treatment groups to receive daily doses of either AKR-501 2.5, 5, 10 or 20 mg or placebo for 28 days, respectively. Each AKR-501 dosing group will consist of 15 patients while the placebo group will consist of 5 patients. All study patients will be evaluated weekly (Days 3, 5, 7, 14, 21 and 28) for safety, efficacy, and (Days 7, 14, 21, and 28) AKR-501 pharmacokinetics while receiving study treatment with a final assessment for safety and effectiveness to be done 2 weeks after the last study dose (Day 42).

At the completion of Visit Day 28±1, patients who complete 28±1 days of study dosing will be assessed for eligibility to enroll into the rollover Study 501-CL-004 based on this visit.

  Eligibility

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

Inclusion Criteria:

  1. Men and women ≥ 18 years of age.
  2. Confirmed diagnosis of ITP according to American Society of Hematology (ASH) Guidelines ≥ 3 months prior to Day 1.
  3. If ≥ 60 years old, must have had either a bone marrow biopsy consistent with ITP within past 3 years or a good response (platelet count > 100,000/mm^3) to a previous ITP treatment.
  4. Are refractory or relapsed after at least one prior ITP therapy (patients who are refractory and failed to achieve a platelet count ≥ 50,000/mm^3 despite steroids or ≥ 30,000/mm^3 to other prior ITP therapies, such as splenectomy, danazol, or immunosuppressive drugs. For patients who are relapsed, the platelet counts must be below 50,000/mm^3 if using steroids or 30,000/mm^3 if not prescribed steroids.)
  5. Patients receiving maintenance corticosteroids may be enrolled, as long as the corticosteroids have been administered at a stable dose (same milligram amount ± 10%) for ≥ 2 weeks prior to Screening Visit A and the investigator does not foresee the need to change the steroid dose during study participation. Patients should remain on this stable corticosteroid dose during study participation.
  6. Patients receiving stable dosages of cyclosporine A, mycophenolate mofetil, azathioprine or danazol may also be enrolled. The dosages of all these medications must be stable for at least 3 months prior to AKR-501 administration.
  7. Platelet count:

    • Patients not receiving steroids (no steroid treatment for > 2 weeks prior to the Screening Visit A): platelets < 30,000/mm^3 at Screening Visit A and within 96 hours prior to Day 1 (Screening Visit B)
    • Patients receiving steroids: platelets < 50,000/mm^3 at Screening Visit A and within 96 hours prior to Day 1 (Screening Visit B).
  8. Women of child-bearing potential must have a negative pregnancy test at Screening Visit A and Screening Visit B. (Childbearing potential is defined as any woman who has not been surgically sterilized and is premenopausal or peri-menopausal i.e., any menstrual flow within 12 months of Screening Visit A).
  9. Women of child-bearing potential and all men must agree to practice a medically approved form of contraception (one of the following must be used: condoms (male or female) with a spermicidal agent, diaphragm, or cervical cap with a spermicidal agent, IUD, hormonal contraception, abstinence).
  10. Willing and able to provide written informed consent before any study-related procedure.

Exclusion Criteria:

  1. Women who are pregnant and/or lactating.
  2. Splenectomy procedure performed 4 weeks prior to AKR-501 administration.
  3. Use of the following drugs or treatments prior to Day 1:

    • Within 3 months - Rituximab;
    • Within 2 weeks - Aspirin or Aspirin-containing compounds, Salicylates, Anticoagulants, clopidogrel, ticlopidine, Rh0(D) Immune Globulin (WinRho®), or intravenous immunoglobulin (IVIG).
  4. Participation in a clinical trial involving any investigational agent within 4 weeks of Day 1.
  5. Exposure to eltrombopag or AMG -531.
  6. Significant medical conditions or diseases as determined by the Investigator (e.g., clinically active systemic lupus erythematosus; known or suspected HIV infection; acute hepatitis or clinically active chronic hepatitis; lymphoproliferative disease; congestive heart failure).
  7. History of cardiovascular disease (e.g., angina, unstable angina, myocardial infraction, coronary artery stent placement, angioplasty, coronary artery bypass grafting).
  8. History of thromboembolic disease (e.g., transient ischemic attack [TIA], stroke [CVA], pulmonary embolism [PE]).
  9. History of deep venous thrombosis (DVT).
  10. History of lupus anticoagulant or anticardiolipin antibody syndrome or positive anti b2 glycoprotein antibody.
  11. History of any medical condition where systemic anticoagulation was required for more than 6 months.
  12. Laboratory abnormalities:

    • Hemoglobin < 12.5 g/dL for men and < 11.5 g/dL for women. If anemia is clearly related to ITP, for example excessive blood loss, then that patient may be enrolled without the need for a waiver after discussion with the Sponsor's medical monitor
    • White blood cell count (WBC) < lower limit of normal
    • Absolute neutrophil count (ANC) < 1000/mm^3
    • Prothrombin time (PT) > 1.25 x upper limit of normal
    • Partial thromboplastin time (PTT) > 1.25 x upper limit of normal
    • Total bilirubin > 3 x upper normal limit
    • Alanine transaminase (ALT) > 3 x upper normal limit
    • Aspartate transaminase (AST) > 3 x upper normal limit
    • Creatinine > 1.5x upper normal limit
    • Blood urea nitrogen (BUN) > 1.5 x upper normal limit
    • HIV positive
    • IgM HAV positive, Hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV) positive.
  13. History of, or current alcohol or drug abuse likely to interfere with ability to comply with protocol.

    requirements or give informed consent, as determined by the Investigator.

  14. History of, or current psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent, as determined by the Investigator.
  15. Currently taking any of the following medications: Rituximab, Aspirin or Aspirin-containing compounds, Salicylates, Anticoagulants, clopidogrel, ticlopidine, Rh0(D) Immune Globulin (WinRho®), or intravenous immunoglobulin (IVIG).
  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: NCT00441090

  Show 25 Study Locations
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Pei-Ran Ho, MD Eisai Inc.
  More Information

Additional Information:
No publications provided by Eisai Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00441090     History of Changes
Other Study ID Numbers: AKR-501-CL-003
Study First Received: February 27, 2007
Last Updated: October 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Chronic Idiopathic Thrombocytopenic Purpura
Idiopathic Thrombocytopenic Purpura
ITP

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

ClinicalTrials.gov processed this record on November 27, 2014