A Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Fidaxomicin in Healthy Male Japanese and Caucasian Subjects

• ClinicalTrials.gov Identifier: NCT01813448
• Recruitment Status: Completed
• First Posted: March 19, 2013
• Last Update Posted: May 21, 2014
• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborator: Cubist Pharmaceuticals LLC
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information

• First Submitted Date: March 15, 2013
• First Posted Date: March 19, 2013
• Last Update Posted Date: May 21, 2014
• Study Start Date: February 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2013)

• Pharmacokinetics (PK) of fidaxomicin in plasma (single dose): Lag time (tlag) [ Time Frame: Days 1-5 (14 times) ]
• PK of fidaxomicin plasma (single dose): Time to attain maximum concentration (tmax) [ Time Frame: Days 1-5 (14 times) ]
• PK of fidaxomicin in plasma (single dose): Maximum Concentration (Cmax) [ Time Frame: Days 1-5 (14 times) ]
• PK of fidaxomicin in plasma (single dose): Area Under the Plasma Concentration - Time Curve (AUC) from Time Zero to Time of Last Measurable Concentration (AUClast) [ Time Frame: Days 1-5 (14 times) ]
• PK of fidaxomicin in plasma (single dose): AUC - Time Curve from Time Zero to Infinity (aucinf) [ Time Frame: Days 1-5 (14 times) ]
• PK of fidaxomicin in plasma (single dose): AUC - Time Curve from Time Zero to 12 hours (AUC 0-12h) [ Time Frame: Days 1-5 (14 times) ]
• PK of fidaxomicin in plasma (single dose): Total Body Clearance after Single Dose (CL/F) [ Time Frame: Days 1-5 (14 times) ]
• PK of fidaxomicin in plasma (single dose): Apparent Volume of Distribution During Terminal Phase (Vz/F) [ Time Frame: Days 1-5 (14 times) ]
• PK of fidaxomicin in plasma (last dose): Apparent Volume of Distribution During Terminal Phase (Vz/F) [ Time Frame: Days 15-17 (11 times) ]
• PK of fidaxomicin in plasma (single dose): Apparent Terminal elimination Half-life (t 1/2) [ Time Frame: Days 1-5 (14 times) ]
  Single Dose
• PK of fidaxomicin in plasma (last dose): Apparent Terminal elimination Half-life (t 1/2) [ Time Frame: Days 15-17 (11 times) ]
  Single Dose
• PK of fidaxomicin in plasma (single dose): Trough levels [ Time Frame: Days 6, 7, 10, and 12 (pre-morning dose) ]
• PK of fidaxomicin in plasma (last dose): tmax at Steady State (tmax, ss) [ Time Frame: Days 15-17 (11 times) ]
  Last Dose
• PK of fidaxomicin in plasma (last dose): Cmax at Steady State (Cmax, ss) [ Time Frame: Days 15-17 (11 times) ]
  Last Dose
• PK of fidaxomicin in plasma (last dose): AUC Over the dosing Interval (AUCtau) [ Time Frame: Days 15-17 (11 times) ]
• PK of fidaxomicin in plasma (last dose): CL/F at Steady State (CL/F ss) [ Time Frame: Days 15-17 (11 times) ]
• PK of fidaxomicin in plasma (last dose): Peak: Trough Ratio (PTR) [ Time Frame: Days 15-17 (11 times) ]
• PK of fidaxomicin in plasma (last dose): Accumulation Ratio (Racc) [ Time Frame: Days 15-17 (11 times) ]
• PK of fidaxomicin in plasma (last dose): Pre-dose Plasma Concentration Determined Directly from the Concentration-Time Profile (Ctrough) [ Time Frame: Days 15-17 (11 times) ]
• PK of fidaxomicin in urine (last dose): Cumulative Amount of Drug Excreted in the urine from Time Zero to Time of Last Measurable Concentration (Aelast) [ Time Frame: Days 1-5 (6 times) ]
• PK of fidaxomicin in urine (single dose): Percent Fraction of Administered Drug Excreted Unchanged in the urine from Time Zero to Time of Last Measurable Concentration (% Aelast ) [ Time Frame: Days 1-5 (6 times) ]
• PK of fidaxomicin in urine (single dose): Cumulative Amount of Drug Excreted in the Urine from time Zero to Infinity after Single Dose (Aeinf) [ Time Frame: Days 1-5 (6 times) ]
• PK of fidaxomicin in urine (single dose): Percent Fraction of administered drug excreted unchanged in the urine from time Zero to Infinity after Single Dose (% Aeinf) [ Time Frame: Days 1-5 (6 times) ]
• PK of fidaxomicin in urine (single dose): Renal Clearance (CL/R [ Time Frame: Days 1-5 (6 times) ]
• PK of fidaxomicin in urine (last dose): Cumulative Amount of Drug Excreted in the urine over the dosing Interval at Steady State (Aetau) [ Time Frame: Day 15 (1 time) ]
• PK of fidaxomicin in urine (last dose): Percent Fraction of Administered Drug Excreted Unchanged in the Urine over the Dosing Interval at Steady State (% Aetau) [ Time Frame: Day 15 (1 time) ]
• PK of fidaxomicin in urine (last dose): Renal Clearance at Steady State (CLR,ss) [ Time Frame: Day 15 ( 1 time) ]
• PK of fidaxomicin in feces (single dose): Amount of Drug Excreted in the Feces (Ae) [ Time Frame: Days 1-5 (5 times) ]
• PK of fidaxomicin in feces (last dose): Amount of Drug Excreted in the Feces (Ae) [ Time Frame: Days 15-17 (first bowel movement (BM) following the last dose to be collected) ]
• PK of fidaxomicin in feces (single dose): Percent Fraction of Administered Drug Excreted Unchanged in the Feces (%Ae) [ Time Frame: Days 1-5 (5 times) ]
• PK of fidaxomicin in feces (last dose): Percent Fraction of Administered Drug Excreted Unchanged in the Feces (%Ae) [ Time Frame: Days 15-17 (first BM following the last dose to be collected) ]

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Fidaxomicin in Healthy Male Japanese and Caucasian Subjects
• Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Fidaxomicin in Healthy Male Japanese and Caucasian Subjects
• Brief Summary: The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of single and multiple ascending doses of fidaxomicin in healthy subjects. This study will also compare the safety, tolerability and PK of single and multiple doses of fidaxomicin in healthy Japanese and Caucasian subjects.

Detailed Description

Eligible subjects will check into the unit on Day-2 and remain confined to the clinical unit until Day 17.

Cohorts 2 and 3, which may run in parallel, will only be enrolled after review of the available safety data of Cohort 1 by the Safety Review Team.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Condition

• Pharmacokinetics of Fidaxomicin
• Healthy Subjects

Intervention

• Drug: Fidaxomicin
  oral
  Other Names:

  • OPT-80
  • Dificlir
  • Dificid
• Drug: Placebo
  oral

Study Arms

• Experimental: Cohort 1: Fidaxomicin low dose in Japanese males
  Intervention: Drug: Fidaxomicin
• Experimental: Cohort 2: Fidaxomicin high dose in Japanese males
  Intervention: Drug: Fidaxomicin
• Experimental: Cohort 3: Fidaxomicin high dose in Caucasian males
  Intervention: Drug: Fidaxomicin
• Placebo Comparator: Matching Placebo in Caucasian males
  Intervention: Drug: Placebo
• Placebo Comparator: Matching Placebo in Japanese males
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 15, 2013): 36
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male subject and their female spouse/partners who are 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 continuing throughout the study period and for 90 days after final study drug administration

2. Male subject must not donate sperm starting at Screening and throughout the study period and for at least 90 days after final study drug administration

   Inclusion Criteria for Japanese Subjects

3. The subject is a healthy Japanese male who maintains the Japanese lifestyle, including diet and has a body mass index (BMI) of 18.0 to 28.0 kg/m2, inclusive.

   Inclusion Criteria for Caucasian Subjects

4. The subject is a healthy Caucasian male and has a BMI of 18.0 to 32.0 kg/m2, inclusive

Exclusion Criteria:

1. The subject has any clinically significant disease history
2. The subject has a history of or current C.difficile infection or history of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (history of appendectomy, hernia repair, and/or cholecystectomy is permitted)
3. The subject has any clinically significant abnormality
4. The subject has a resting (i.e., seated for 5 minutes) pulse <40 or >90 beats per minute (bpm) at Screening or Day -2
5. The subject has hypertension (defined as seated systolic blood pressure [SBP] >140 mmHg or seated diastolic blood pressure [DBP] >90 mmHg) or hypotension (defined as seated SBP <90 mmHg or seated DBP <50 mmHg) at Screening or Day -2
6. The subject has/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic check-in on Day -2
7. The subject has a history of chronic diarrhea or constipation
8. The subject has a positive result for hepatitis C antibodies or hepatitis B surface antigen at Screening or has a known positive history of human immunodeficiency virus (HIV)
9. The subject has a known or suspected allergy or hypersensitivity to any of the components of fidaxomicin, the macrolide antibacterial class of compounds, or a history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 20 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01813448
• Other Study ID Numbers: 2819-CL-3001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Astellas Pharma Global Development, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Cubist Pharmaceuticals LLC

Investigators

• Study Director: Sr. Medical Director; Astellas Pharma Global Development, Inc.

• PRS Account: Astellas Pharma Inc
• Verification Date: May 2014