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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: tafamidis; Drug: rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Brussels Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rosuvastatin and tafamidis fixed sequence; 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; 61 mg capsule; Other Names: Vyndaqel; Drug: rosuvastatin; 10 mg tablet; Other Names: Crestor

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2020
• Primary Completion (Actual): August 10, 2020
• Study Completion (Actual): August 10, 2020

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: January 31, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): September 10, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: B3461075

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No