A Drug-Drug Interaction Study To Estimate The Effect Of Tafamidis On Rosuvastatin Pharmacokinetics

Study Overview
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Brief Summary
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Each subject will be given a single oral dose of rosuvastatin on Day 1 in Period 1. In Period 2, after a washout period of at least 5 days, each subject will receive oral doses of tafamidis twice daily (BID) on days 1 and 2, followed by tafamidis once daily (QD) on days 3 to 9 with an oral dose of rosuvastatin on Day 7. Rosuvastatin exposures will be compared between Periods 1 and 2 to estimate the effect of tafamidis on rosuvastatin PK in healthy subjects.

Official Title
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A PHASE 1, OPEN LABEL, TWO-PERIOD, TWO-TREATMENT, FIXED-SEQUENCE STUDY TO ESTIMATE THE EFFECT OF A MULTIPLE ORAL DOSE OF TAFAMIDIS ON ROSUVASTATIN PHARMACOKINETICS IN HEALTHY PARTICIPANTS

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: tafamidis
* Drug: rosuvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants must be 18 to 60 years of age, inclusive, at the time of signing the informed consent document (ICD) Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiovascular tests Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb) Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: History of hypersensitivity to rosuvastatin., asymptomatic, seasonal allergies at the time of dosing). Use of CYP2C19 inhibitors (eg, fluconazole, fluoxetine, fluvoxamine, ticlopidine omeprazole, voriconazole, cimetidine, esomeprazole, and felbamate) or inducers (eg, rifampin, ritonavir, efavirenz, enzalutamide, phenytoin, and St. John's Wort) within 28 days or 5 half-lives (whichever is longer) prior to dosing. Use of CYP3A4 inhibitors (eg, ketoconazole, ciprofloxacin, diltiazem) or other inducers (eg, phenytoin, carbamazepine) within 28 days or 5 half-lives (whichever is longer) prior to dosing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rosuvastatin and tafamidis fixed sequence<br>Period 1: rosuvastatin 10 mg (single oral administration) Washout Period 2: tafamidis 61 mg capsule(multiple doses, twice a day) + rosuvastatin 10 mg (single oral administration) | Drug: tafamidis<br>* 61 mg capsule<br>* Other names: Vyndaqel;Drug: rosuvastatin<br>* 10 mg tablet<br>* Other names: Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time profile from time 0 extrapolated to infinity (AUCinf) for rosuvastatin | AUClast + (Clast/kel) | Hours 0, at 30 minutes and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose in Periods 1 and 2. | 
| Apparent renal clearance (CLr) for rosuvastatin | Ae/AUClast for extravascular dosing | Hours 0, at 30 minutes and 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose in Periods 1 and 2 for AUClast. For Ae, hours 0-24, 24-48, 48-72 hours post-dose in Periods 1 and 2. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with a clinically significant change in vital sign measurements from baseline |  | Baseline through Day 10 of period 2 | 
| Number of subjects with a clinically significant change in laboratory tests from baseline |  | Baseline through Day 10 of period 2 | 
| Number of subjects with treatment emergent adverse events |  | Baseline through Day 28 follow up |