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

NCT00441090 | Completed Phase 2 Results

• 1 other identifier: AKR-501-CL-003
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 25

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).

Conditions

Chronic Idiopathic Thrombocytopenic Purpura; Purpura, Thrombocytopenic, Idiopathic

Keywords

Chronic Idiopathic Thrombocytopenic Purpura; Idiopathic Thrombocytopenic Purpura; ITP

Outcome Measures

Primary Outcomes (1)

• Responder Rate (RR) to Avatrombopag on 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 RR was defined as the percentage of participants with a Day 1 platelet count of less than 30,000/milliliter (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).

  Day-4 to Day 1, Baseline, Day 28

Secondary Outcomes (5)

• 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

Other Outcomes (1)

• To Evaluate the Pharmacokinetics (PK) and the Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship of Avatrombopag in Patients With ITP.

  Days 7, 14, 21 and 28

Study Arms (2)

Avatrombopag tablets

EXPERIMENTAL

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

Drug: Avatrombopag tablets

Placebo tablet

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Placebo DRUG

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

Placebo tablet

Avatrombopag tablets DRUG

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

Also known as: AKR-501, E5501, YM477

Avatrombopag tablets

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ≥ 18 years of age.
• Confirmed diagnosis of ITP according to American Society of Hematology (ASH) Guidelines ≥ 3 months prior to Day 1.
• 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.
• 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.)
• 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.
• 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.
• 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).
• 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).
• 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).
• Willing and able to provide written informed consent before any study-related procedure.

You may not qualify if:

• Women who are pregnant and/or lactating.
• Splenectomy procedure performed 4 weeks prior to AKR-501 administration.
• 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).
• Participation in a clinical trial involving any investigational agent within 4 weeks of Day 1.
• Exposure to eltrombopag or AMG -531.
• 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).
• History of cardiovascular disease (e.g., angina, unstable angina, myocardial infraction, coronary artery stent placement, angioplasty, coronary artery bypass grafting).
• History of thromboembolic disease (e.g., transient ischemic attack \[TIA\], stroke \[CVA\], pulmonary embolism \[PE\]).
• History of deep venous thrombosis (DVT).
• History of lupus anticoagulant or anticardiolipin antibody syndrome or positive anti b2 glycoprotein antibody.
• History of any medical condition where systemic anticoagulation was required for more than 6 months.
• 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

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (25)

Pacific Cancer Medical Center, Inc

Anaheim, California, 92801, United States

Location

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

Bay Area Cancer Research Group, LLC

Concord, California, United States

Location

Pacific Coast Hematology/Oncology Medical Group Inc.

Fountain Valley, California, 92708, United States

Location

University of California Irvine Cancer Center

Orange, California, 92618, United States

Location

Davis, Posteraro and Wasser, MDs, LLP

Manchester, Connecticut, 06105, United States

Location

Georgetown University

Washington D.C., District of Columbia, United States

Location

Florida Cancer Institute

New Port Richey, Florida, 34655, United States

Location

Columbus Clinic, PC

Columbus, Georgia, 31901, United States

Location

John H. Stroger, Jr. Hospital of Cook County, Div. of Hematology and Oncology

Chicago, Illinois, 60612, United States

Location

Comprehensive Bleeding Disorders Center

Peoria, Illinois, 61614, United States

Location

Cancer Care Center, Inc.

New Albany, Indiana, 47150, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Capitol Comprehensive Cancer Care Clinic

Jefferson City, Missouri, 65109, United States

Location

Kansas City Cancer Center, LLC

Kansas City, Missouri, 64131, United States

Location

UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

New York Presbyterian Hospital, Weill Medical College of Cornell University

New York, New York, 10032, United States

Location

Emerywood Oncology and Hematology

High Point, North Carolina, 27262, United States

Location

Mid Ohio Oncology/Hematology, Inc., dba The Mark H. Zangmeister Center

Columbus, Ohio, 43219, United States

Location

UPENN

Philadelphia, Pennsylvania, 19104, United States

Location

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Cancer Centers of the Carolina

Greenville, South Carolina, 29605, United States

Location

Puget Sound Blood Center

Seattle, Washington, 98014, United States

Location

Related Publications (1)

• Bussel JB, Kuter DJ, Aledort LM, Kessler CM, Cuker A, Pendergrass KB, Tang S, McIntosh J. A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood. 2014 Jun 19;123(25):3887-94. doi: 10.1182/blood-2013-07-514398. Epub 2014 May 6.

  PMID: 24802775 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

avatrombopag

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai Inc.

1-888-422-4743

Study Officials

• Pei-Ran Ho, MD

  Eisai Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2007
• First Posted: February 28, 2007
• Study Start: February 1, 2007
• Primary Completion: January 1, 2009
• Study Completion: June 1, 2009
• Last Updated: March 7, 2018
• Results First Posted: January 4, 2018

Record last verified: 2018-02

Locations

US (25)