Clinical trial NCT02083627: A Study to Assess the Effects of Multiple Doses of Fidaxomicin on a Single Dose of Rosuvastatin in Healthy Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug-Drug Interaction (DDI)
Intestinal Absorption
Healthy Subjects
Pharmacokinetics of Rosuvastatin
Pharmacokinetics of Fidaxomicin
Keywords: Pharmacokinetics
Drug-Drug Interaction
Intestinal Absorption
Fidaxomicin
Rosuvastatin
Multiple Doses
Single Doses
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
First posted: 2014-03-11
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Effect of multiple doses of fidaxomicin on the single dose pharmacokinetics of rosuvastatin as measured by maximum observed concentration
timeFrame: Day 1-6 (sequence1/period1) & Day 13-18 (sequence1/period2) Day 6-11 (sequence2/period1) & Day 14-19 (sequence2/period2)
measure: 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
timeFrame: Day 1-6 (sequence1/period1) & Day 13-18 (sequence1/period2) Day 6-11 (sequence2/period1) & Day 14-19 (sequence2/period2)
Secondary outcomes:
measure: Effect of multiple doses of fidaxomicin on the single dose pharmacokinetic profile of rosuvastatin
timeFrame: Day 1-6 (sequence1/period1) & Day 13-18 (sequence1/period2) Day 6-11 (sequence2/period1) & Day 14-19 (sequence2/period2)
measure: Safety and tolerability of multiple doses of fidaxomicin in the presence of a single dose of rosuvastatin
timeFrame: Screening (Day -22 to -2) to ESV (7 to 14 days after (early) discharge)
measure: PK of multiple doses of fidaxomicin and its metabolite OP-1118
timeFrame: Day 9-15 (sequence 1/period2) & Day 2-8 (sequence2/period1)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Parexel GmbH
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Medical Monitor
role: STUDY_DIRECTOR
References: