Effect of Repeated Doses of DS-8500a on Pharmacokinetics of Rosuvastatin in Healthy Volunteers

An Open-label, Fixed Sequence, Two-period Study to Evaluate the Effects of Repeated Doses of DS-8500a on the Pharmacokinetics of Rosuvastatin in Healthy Subjects.

The primary purpose of this study is to assess the effect of repeated doses of DS-8500a on the single dose pharmacokinetics (PK) of rosuvastatin.

The total length of time (from screening to follow-up) for each participant is approximately 7 weeks.

It is expected that repeated oral doses of DS-8500a will not have a significant effect on the pharmacokinetics of a single dose of rosuvastatin.

Study Overview

• Status: Completed
• Conditions: Drug Pharmacokinetics in Healthy Volunteers
• Intervention / Treatment: Drug: DS-8500a; Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials (WCT) Early Phase Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Is healthy and of non-child-bearing potential
• Has a body mass index of 18-30 kg/m^2
• Has negative results for drugs of abuse, cotinine (smoking) and alcohol at screening
• Has signed informed consent and agreed to comply with all study requirements

Exclusion Criteria:

• Has history or current evidence of clinically significant cardiac, hepatic, renal, pulmonary, endocrine/metabolic, neurologic, infectious, gastrointestinal , hematologic, or oncologic disease as determined by screening history, physical examination, laboratory test results, or 12-lead ECG
• Has any other condition detailed in the protocol, or that in the opinion of the Investigator, precludes participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All Participants; In treatment Period 1 (Day 1 through Day 4), on Day 1, participants receive a single dose of rosuvastatin 10 mg orally with food, and in Period 2 (Day 1 through Day 16), starting on Day 1, participants receive DS-8500a 75 mg orally qd with food for 16 days with concomitant administration of a single dose of rosuvastatin 10 mg qd on Day 14. In both the periods, rosuvastatin and DS-8500a are administered after an overnight fast of 8 hours and within 10 minutes after consuming a standardized breakfast of 500 calories.

Drug: DS-8500a; DS-8500a is provided as three 25-mg tablets for oral administration; Other Names: Experimental product; Drug: Rosuvastatin; Rosuvastatin is provided as a 10-mg tablet for oral administration; Other Names: Crestor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma drug concentration (Cmax) for single dose rosuvastatin	on Day 1 of Period 1 and Day 14 of Period 2
Time of maximum observed concentration (Tmax) for single dose rosuvastatin	on Day 1 of Period 1 and Day 14 of Period 2
Area under the plasma concentration time curve (AUC) from time 0 to the last quantifiable concentration (AUClast) for single dose rosuvastatin	on Day 1 of Period 1 and Day 14 of Period 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax for DS-8500a and its metabolites	Categories: DS-8500a, A209-3952, A210-2519, and A210-7951	on Day 1 (for single dose) and Day 16 (for multiple dose) of Period 2
Tmax for DS-8500a and its metabolites	Categories: DS-8500a, A209-3952, A210-2519, and A210-7951	on Day 1 (for single dose) and Day 16 (for multiple dose) of Period 2
AUC from time 0 to 24 hours (AUC0-24) for DS-8500a and its metabolites	Categories: DS-8500a, A209-3952, A210-2519, and A210-7951	on Day 1 (for single dose) and Day 16 (for multiple dose) of Period 2
Metabolite to parent (M:P) AUC0-24 ratios for DS-8500a and its metabolites	Categories: A209-3952:DS-8500a, A210-2519:DS-8500a, and A210-7951:DS-8500a	on Day 1 (for single dose) and Day 16 (for multiple dose) of Period 2
Minimum observed analyte concentration that was just prior to the beginning of the dosing interval (Ctrough)		Days 2, 3, 5, 7, 10, 14, and 16 of Period 2
Cmax at steady state (Cmax,ss)		Day 16 of Period 2
AUC during the 24 hour dosing interval (AUCtau)		Day 16 of Period 2
Accumulation ratio (AccRatio)		Day 16 of Period 2
Tmax at steady state (Tmax,ss)		Day 16 of Period 2

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Publications and helpful links

General Publications

• Maekawa Y, Furuie H, Kato M, Myobatake Y, Kamiyama E, Watanabe A, Shiosakai K, Taguchi T, Bass R, Zhou J, Dishy V, Warren V, Vashi V, Ishizuka H. Effect of DS-8500a, a Novel G Protein-Coupled Receptor 119 Agonist, on the Pharmacokinetics of Rosuvastatin and Atorvastatin in Healthy Subjects. Clin Drug Investig. 2019 Oct;39(10):967-978. doi: 10.1007/s40261-019-00825-1.

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2015
• Primary Completion (Actual): July 6, 2015
• Study Completion (Actual): July 6, 2015

Study Registration Dates

• First Submitted: October 5, 2018
• First Submitted That Met QC Criteria: October 5, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Firuglipel
• Other Study ID Numbers: DS8500-A-U105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No