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

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).

Sponsors

Lead Sponsor: Eisai Inc.

Source Eisai Inc.
Brief Summary

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

Detailed Description

This is a Phase 2, multi-center, double-blind, randomized, placebo-controlled, dose-ranging, parallel-group study. The pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) relationship of avatrombopag will also be studied. Approximately 65 eligible participants 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 avatrombopag 2.5, 5, 10 or 20 mg or placebo for 28 days, respectively. Each avatrombopag dosing group will consist of 15 participants while the placebo group will consist of 5 participants. All study participants will be evaluated weekly (Days 3, 5, 7, 14, 21 and 28) for safety, efficacy, and (Days 7, 14, 21, and 28) avatrombopag PK 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, participants who complete 28±1 days of study dosing will be assessed for eligibility to enroll into the rollover Study 501-CL-004 (NCT00625443) based on this visit.

Overall Status Completed
Start Date February 2007
Completion Date June 2009
Primary Completion Date January 2009
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Responder Rate (RR) to Avatrombopag on Day 28 Day-4 to Day 1, Baseline, Day 28
Secondary Outcome
Measure Time Frame
Change in Platelet Count From Baseline Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, Day 28
Responder Rate to Avatrombopag by Visit Day -4 to Day 1, Baseline, Day 7, Day 14, and Day 21
Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28
Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28
Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28
Enrollment 64
Condition
Intervention

Intervention Type: Drug

Intervention Name: Placebo

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

Arm Group Label: Placebo tablet

Intervention Type: Drug

Intervention Name: Avatrombopag tablets

Description: Avatrombopag tablets 2.5, 5, 10 and 20 mg taken orally once daily for 28 days.

Arm Group Label: Avatrombopag tablets

Eligibility

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).

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Pei-Ran Ho, MD Study Director Eisai Inc.
Location
Facility:
Pacific Cancer Medical Center, Inc | Anaheim, California, 92801, United States
Comprehensive Blood and Cancer Center | Bakersfield, California, 93309, United States
Bay Area Cancer Research Group, LLC | Concord, California, United States
Pacific Coast Hematology/Oncology Medical Group Inc. | Fountain Valley, California, 92708, United States
University of California Irvine Cancer Center | Orange, California, 92618, United States
Davis, Posteraro and Wasser, MDs, LLP | Manchester, Connecticut, 06105, United States
Georgetown University | Washington, District of Columbia, United States
Florida Cancer Institute | New Port Richey, Florida, 34655, United States
Columbus Clinic, PC | Columbus, Georgia, 31901, United States
John H. Stroger, Jr. Hospital of Cook County, Div. of Hematology and Oncology | Chicago, Illinois, 60612, United States
Comprehensive Bleeding Disorders Center | Peoria, Illinois, 61614, United States
Cancer Care Center, Inc. | New Albany, Indiana, 47150, United States
Johns Hopkins University | Baltimore, Maryland, 21287, United States
Massachusetts General Hospital | Boston, Massachusetts, 02114, United States
Capitol Comprehensive Cancer Care Clinic | Jefferson City, Missouri, 65109, United States
Kansas City Cancer Center, LLC | Kansas City, Missouri, 64131, United States
UMDNJ - Robert Wood Johnson Medical School | New Brunswick, New Jersey, 08901, United States
Mount Sinai Medical Center | New York, New York, 10029, United States
New York Presbyterian Hospital, Weill Medical College of Cornell University | New York, New York, 10032, United States
Emerywood Oncology and Hematology | High Point, North Carolina, 27262, United States
Mid Ohio Oncology/Hematology, Inc., dba The Mark H. Zangmeister Center | Columbus, Ohio, 43219, United States
UPENN | Philadelphia, Pennsylvania, 19104, United States
Western Pennsylvania Hospital | Pittsburgh, Pennsylvania, 15212, United States
Cancer Centers of the Carolina | Greenville, South Carolina, 29605, United States
Puget Sound Blood Center | Seattle, Washington, 98014, United States
Location Countries

United States

Verification Date

February 2018

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Avatrombopag tablets

Type: Experimental

Description: 2.5, 5, 10 or 20 mg tablets 1 tablet taken orally once daily for 28 days

Label: Placebo tablet

Type: Placebo Comparator

Description: 2.5, 5, 10, or 20 mg tablets 1 tablet taken orally once daily for 28 days

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov