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

Purpura, Thrombocytopenic, Idiopathic Clinical Trial

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00441090
• Other study ID #: AKR-501-CL-003
• Status: Completed
• Phase: Phase 2
• First received: February 27, 2007
• Last updated: February 6, 2018
• Start date: February 2007
• Est. completion date: June 2009

Study information

• Verified date: February 2018
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: June 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Chronic Idiopathic Thrombocytopenic Purpura
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

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

Locations

Country	Name	City	State
United States	Pacific Cancer Medical Center, Inc	Anaheim	California
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Johns Hopkins University	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	John H. Stroger, Jr. Hospital of Cook County, Div. of Hematology and Oncology	Chicago	Illinois
United States	Columbus Clinic, PC	Columbus	Georgia
United States	Mid Ohio Oncology/Hematology, Inc., dba The Mark H. Zangmeister Center	Columbus	Ohio
United States	Bay Area Cancer Research Group, LLC	Concord	California
United States	Pacific Coast Hematology/Oncology Medical Group Inc.	Fountain Valley	California
United States	Cancer Centers of the Carolina	Greenville	South Carolina
United States	Emerywood Oncology and Hematology	High Point	North Carolina
United States	Capitol Comprehensive Cancer Care Clinic	Jefferson City	Missouri
United States	Kansas City Cancer Center, LLC	Kansas City	Missouri
United States	Davis, Posteraro and Wasser, MDs, LLP	Manchester	Connecticut
United States	Cancer Care Center, Inc.	New Albany	Indiana
United States	UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Florida Cancer Institute	New Port Richey	Florida
United States	Mount Sinai Medical Center	New York	New York
United States	New York Presbyterian Hospital, Weill Medical College of Cornell University	New York	New York
United States	University of California Irvine Cancer Center	Orange	California
United States	Comprehensive Bleeding Disorders Center	Peoria	Illinois
United States	UPENN	Philadelphia	Pennsylvania
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Puget Sound Blood Center	Seattle	Washington
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To Evaluate the Pharmacokinetics (PK) and the Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship of Avatrombopag in Patients With ITP.	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.	Days 7, 14, 21 and 28
Primary	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	Change in Platelet Count From Baseline	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. The unit of measure was "K/mm^3", where "K = platelets x 1000 = platelets x 10^3" and "mm^3 = cubic milliliter= microliter".	Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, Day 28
Secondary	Responder Rate to Avatrombopag by Visit	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 RR was summarized by treatment group using the method of LOCF. Day 28 was not included with this data because it was reported as a primary outcome measure.	Day -4 to Day 1, Baseline, Day 7, Day 14, and Day 21
Secondary	Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit	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.	Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28
Secondary	Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit	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.	Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28
Secondary	Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit	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.	Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28