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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Drug Pharmacokinetics in Healthy Volunteers

Intervention / Treatment
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* Drug: DS-8500a
* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Interventional Model Description: Fixed sequence
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Participants<br>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<br>* DS-8500a is provided as three 25-mg tablets for oral administration<br>* Other names: Experimental product;Drug: Rosuvastatin<br>* Rosuvastatin is provided as a 10-mg tablet for oral administration<br>* Other names: Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |