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

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ClinicalTrials.gov Identifier: NCT00441090
Recruitment Status : Completed
First Posted : February 28, 2007
Results First Posted : January 4, 2018
Last Update Posted : January 4, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease Intervention/treatment Phase
Chronic Idiopathic Thrombocytopenic Purpura Purpura, Thrombocytopenic, Idiopathic Drug: Placebo Drug: AKR-501 Tablets Phase 2

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, 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).
Study Start Date : February 2007
Primary Completion Date : January 2009
Study Completion Date : June 2009


Arms and Interventions

Arm Intervention/treatment
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.


Outcome Measures

Primary Outcome Measures :
  1. Responder Rate (RR) to E5501 on Day 28 [ Time Frame: Day 28 ]
    Platelet counts were measured from the participant's blood, which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Day 28. The Responder Rate (RR) was defined as the percentage of participants with a Day 1 platelet count of less than 30,000/mL who reached a platelet count of greater than or equal to 50,000/mL on Day 28 of study medication, together with the percentage of participants using steroids who had a Day 1 platelet count greater than or equal to 30,000/mL but less than 50,000/mL who reached a platelet count of greater than or equal to 20,000/mL higher than their Day 1 platelet count on Day 28 of study medication. The RR was summarized by treatment group using the method of last observation carried forward (LOCF).


Secondary Outcome Measures :
  1. Change in Platelet Count From Baseline [ Time Frame: Day 7, Day 14, Day 21, Day 28 ]
    Platelet counts were measured from the participant's, blood which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28.

  2. Responder Rate (RR) to E5501 by Visit [ Time Frame: Day 7, Day 14, and Day 21 ]
    Platelet counts were measured from the participant's blood, which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, and 21. The responder rate (RR) was defined as the 1) percentage of participants with a Screening Visit B (within 48 hours of Day 1) platelet count of less than 30,000/mL who achieved a platelet count of greater than or equal to 50,000/mL on Day 28 of study medication, along with 2) the percentage of participants using steroids who had a Screening Visit B platelet count greater than or equal to 30,000/mL but less than 50,000/mL who achieved a platelet count of greater than or equal to 20,000/mL higher than their Screening Visit B platelet count on Day 28 of study medication. The RR was summarized by treatment group using the method of last observation carried forward (LOCF). Day 28 was not included with this data because it was reported as a primary outcome measure.

  3. Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit [ Time Frame: Day 7, Day 14, Day 21, and Day 28 ]
    Platelet counts were measured from the participant's blood, which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28.

  4. Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit [ Time Frame: Day 7, Day 14, Day 21, and Day 28 ]
    Platelet counts were measured from the participant's, blood which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28.

  5. Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit [ Time Frame: Day 7, Day 14, Day 21, and Day 28 ]
    Platelet counts were measured from the participant's, blood which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28.


Other Outcome Measures:
  1. To Evaluate the Pharmacokinetics (PK) and the Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship of E5501 in Patients With ITP. [ Time Frame: Days 7, 14, 21 and 28 ]
    Given the sparse PK sampling in this study, PK data from outside studies, which includes healthy subjects, were included to assist in PK model development. As a result this data was not reported with these study results.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00441090


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

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
First Posted: February 28, 2007    Key Record Dates
Results First Posted: January 4, 2018
Last Update Posted: January 4, 2018
Last Verified: December 2017

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

Additional relevant MeSH terms:
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Purpura
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