A Study to Assess the Effects of Multiple Doses of Fidaxomicin on a Single Dose of Rosuvastatin in Healthy Male Subjects

A Phase 1, Open Label, Randomized, Two-way Crossover Study to Evaluate the Effect of Multiple Doses of Fidaxomicin on the Single Dose Pharmacokinetics of Rosuvastatin in Healthy Male Subjects

This study will assess the effect of multiple doses of fidaxomicin on the single dose pharmacokinetics of rosuvastatin in healthy male subjects. Determine the safety and tolerability of multiple doses of fidaxomicin in the presence of a single dose of rosuvastatin in healthy male subjects. Also determine the pharmacokinetics of multiple doses of fidaxomicin and its metabolite OP-1118.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Drug-Drug Interaction (DDI); Intestinal Absorption; Pharmacokinetics of Rosuvastatin; Pharmacokinetics of Fidaxomicin
• Intervention / Treatment: Drug: rosuvastatin; Drug: fidaxomicin

Detailed Description

Sequence 1:

Thirteen subjects receive an oral dose of rosuvastatin on Day 1 in Period 1 and on Day 13 in Period 2 and twice-daily oral doses of fidaxomicin on Days 8 to 17 in Period 2, according to the following treatment schedule:

• Period 1: Subjects receive a single oral dose of rosuvastatin on Day 1, followed by a 5-day pharmacokinetic (PK) sampling period.
• Period 2: The same subjects receive fidaxomicin twice daily for 5 days (Days 8 to 12). On Day 13, a single oral dose of rosuvastatin and an oral dose of fidaxomicin is administered simultaneously in the morning. Twice-daily treatment with fidaxomicin continues until the end of Day 17. Subjects are discharged on Day 18 when all assessments are performed and if there are no medical reasons to prolong the stay.

Sequence 2:

Thirteen subjects receive an oral dose of rosuvastatin on Day 6 in Period 1 and on Day 14 in Period 2. Oral doses of fidaxomicin are administered twice daily for 10 days in Period 1, according to the following treatment schedule:

• Period 1: Subjects receive fidaxomicin twice daily for 5 days (Days 1 to 5). On Day 6, a single oral dose of rosuvastatin is administered simultaneously with an oral dose of fidaxomicin in the morning. Twice daily treatment with fidaxomicin continues until the end of Day 10.
• Period 2: Subjects receive a single oral dose of rosuvastatin on Day 14, followed by a 5-day PK sampling period. Subjects are discharged on Day 19 when all assessments are performed and if there are no medical reasons to prolong the stay.

In both sequences, subjects return to the clinical unit for an End of Study Visit (ESV) 7 to 14 days after (early) discharge.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, D-14059
    • PAREXEL GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• The subject has a Body Mass Index (BMI) range of 18.5 to 30.0 kg/m2. The subject weighs at least 50 kg at Screening.
• Male subject and his female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the study period and for 90 days after final study drug administration.
• The subject must not donate sperm starting at Screening and through-out the study period and for at least 90 days after final study drug administration.

Exclusion Criteria:

• The subject has a history of or current Clostridium difficile infection.
• The subject has a history of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs.
• The subject has an irregular defecation pattern.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1:Single rosuvastatin,multiple fidaxomicin,single rosuvastatin	Drug: rosuvastatin; Oral; Other Names: Crestor®; Drug: fidaxomicin; Oral; Other Names: Dificlir™; DIFICID®
Experimental: 2:Multiple fidaxomicin,single rosuvastatin,single rosuvastatin	Drug: rosuvastatin; Oral; Other Names: Crestor®; Drug: fidaxomicin; Oral; Other Names: Dificlir™; DIFICID®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of multiple doses of fidaxomicin on the single dose pharmacokinetics of rosuvastatin as measured by maximum observed concentration	Cmax (maximum observed concentration)	Day 1-6 (sequence1/period1) & Day 13-18 (sequence1/period2) Day 6-11 (sequence2/period1) & Day 14-19 (sequence2/period2)
Effect of multiple doses of fidaxomicin on the single dose pharmacokinetics of rosuvastatin as measured by area under the concentration time curve from time zero extrapolated to infinity	AUCinf (area under the concentration time curve from time zero extrapolated to infinity)	Day 1-6 (sequence1/period1) & Day 13-18 (sequence1/period2) Day 6-11 (sequence2/period1) & Day 14-19 (sequence2/period2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of multiple doses of fidaxomicin on the single dose pharmacokinetic profile of rosuvastatin	AUClast (Area under the concentration time curve from time point zero to last quantifiable concentration), CL/F (apparent clearance following oral administration), tmax (time to attain Cmax (maximum observed concentration), t1/2 (terminal elimination half-life), Vz/F (apparent volume of distribution during terminal phase)	Day 1-6 (sequence1/period1) & Day 13-18 (sequence1/period2) Day 6-11 (sequence2/period1) & Day 14-19 (sequence2/period2)
Safety and tolerability of multiple doses of fidaxomicin in the presence of a single dose of rosuvastatin	Adverse Events (AE), vital signs, laboratory tests, 12-lead Electrocardiogram (ECG)	Screening (Day -22 to -2) to ESV (7 to 14 days after (early) discharge)
PK of multiple doses of fidaxomicin and its metabolite OP-1118	tmax (time to attain Cmax (maximum observed concentration), AUCtau (area under the concentration time curve over a dosing interval), Ctrough (measured concentration at the end of a dosing interval (taken directly before next administration))	Day 9-15 (sequence 1/period2) & Day 2-8 (sequence2/period1)

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.
• Collaborators: Cubist Pharmaceuticals LLC

Publications and helpful links

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: March 7, 2014
• First Submitted That Met QC Criteria: March 7, 2014
• First Posted (Estimate): March 11, 2014

Study Record Updates

• Last Update Posted (Estimate): May 21, 2014
• Last Update Submitted That Met QC Criteria: May 19, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Rosuvastatin; Drug-Drug Interaction; Intestinal Absorption; Fidaxomicin; Multiple Doses; Single Doses
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anti-Bacterial Agents; Rosuvastatin Calcium; Fidaxomicin
• Other Study ID Numbers: 2819-CL-2003; 2012-003924-20 (EudraCT Number)