Drug-Drug Interaction Study of Vadadustat With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin

NCT ID: NCT03801733

Last Updated: 2019-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-17
• Study Completion Date: 2018-11-24

Brief Summary

This is a Phase 1, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin and simvastatin in healthy male and female subjects.

Detailed Description

This is a Phase 1, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin in healthy male and female subjects. Thirty-four (34) subjects will be enrolled in Part 1 (rosuvastatin) and based on review of the PK and safety/tolerability data, a decision will be made on whether to proceed with Part 2. Part 2 consists of 2 arms (sulfasalazine and pravastatin). Twenty-six (26) subjects will be enrolled into each arm. Part 3 consists of 2 arms (atorvastatin and simvastatin). Twenty-four (24) subjects will be enrolled into each arm after enrollment in Part 2 is completed. Subjects will be in the study for up to 72 days, including a 28-day screening period, 6-14 day in clinic period, and a 30-day follow up period post last dose. Blood samples for PK analysis will be collected at pre-defined time points throughout the study.

Conditions

Drug Interaction Potentiation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Rosuvastatin, Vadadustat

Part 1: Subjects will receive rosuvastatin 20 mg alone, vadadustat 600 mg alone, followed by rosuvastatin 20 mg in combination with vadadustat 600 mg in a fixed-sequence dosing design.

Group Type: EXPERIMENTAL

Vadadustat

Intervention Type: DRUG

Oral dose of 600 mg QD

Rosuvastatin

Intervention Type: DRUG

Oral Rosuvastatin

Sulfasalazine. Pravastatin, Vadadustat

Part 2, Arm 1: Subjects will receive sulfasalazine 500 mg alone followed by sulfasalazine 500 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.

Part 2, Arm 2: Subjects will receive pravastatin 40 mg alone followed by pravastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.

Group Type: EXPERIMENTAL

Vadadustat

Intervention Type: DRUG

Oral dose of 600 mg QD

Pravastatin

Intervention Type: DRUG

Oral Pravastatin

Sulfasalazine

Intervention Type: DRUG

Oral Sulfasalazine

Atorvastatin, Simvastatin, Vadadustat

Part 3, Arm 1: Subjects will receive atorvastatin 40 mg alone followed by atorvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.

Part 3, Arm 2: 24 subjects will receive simvastatin 40 mg alone followed by simvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.

Group Type: EXPERIMENTAL

Vadadustat

Intervention Type: DRUG

Oral dose of 600 mg QD

Simvastatin

Intervention Type: DRUG

Oral Simvastatin

Atorvastatin

Intervention Type: DRUG

Oral Atorvastatin

Interventions

Vadadustat

Oral dose of 600 mg QD

Intervention Type: DRUG

Simvastatin

Oral Simvastatin

Intervention Type: DRUG

Rosuvastatin

Oral Rosuvastatin

Intervention Type: DRUG

Atorvastatin

Oral Atorvastatin

Intervention Type: DRUG

Pravastatin

Oral Pravastatin

Intervention Type: DRUG

Sulfasalazine

Oral Sulfasalazine

Intervention Type: DRUG

Other Intervention Names

AKB 6548

Eligibility Criteria

Inclusion Criteria

• Healthy Male or female between 18 and 55 years of age, inclusive, at time of informed consent
• Body mass index between 18.0 and 30.0 kg/m2, with a minimum body weight of 45 kg for females and 50 kg for males, inclusive.

Exclusion Criteria

• Current or past clinically significant history of cardiovascular, cerebrovascular, pulmonary, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic, urologic, neurologic, dermatologic, psychiatric, or other major disease. History of cancer (except treated non-melanoma skin cancer) or history of chemotherapy use within 5 years prior to Screening; History of latent or active tuberculosis (TB).
• Positive test results for human immunodeficiency virus (HIV) antibody; 12. Positive test results of hepatitis B surface antigen (HBsAg), or positive hepatitis C virus antibody (HCVab) within 3 months prior to screening, or positive test results for human immunodeficiency virus antibody (HIVab) at Screening
• Taking any prescription medication or over the counter multi-vitamin supplement, or any non-prescription products (including herbal-containing preparations but excluding acetaminophen) within 14 days prior to Day -1.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Akebia Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Akebia Inc

Role: STUDY_DIRECTOR

Akebia Therapeutics

Locations

InVentiv Health Clinique Inc.

Québec, Quebec, Canada

Countries

Canada

Other Identifiers

AKB 6548 CI 0030

Identifier Type: -

Identifier Source: org_study_id