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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01813448
• Other study ID #: 2819-CL-3001
• Status: Completed
• Phase: Phase 1
• First received: March 15, 2013
• Last updated: May 19, 2014
• Start date: February 2013
• Est. completion date: April 2013

Study information

• Verified date: May 2014
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Healthy Subjects
• Pharmacokinetics of Fidaxomicin

Intervention

Drug:
• Fidaxomicin
oral
• Placebo
oral

Locations

Country	Name	City	State
United States	Parexel	Glendale	California

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Cubist Pharmaceuticals LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics (PK) of fidaxomicin in plasma (single dose): Lag time (tlag)		Days 1-5 (14 times)	No
Primary	PK of fidaxomicin plasma (single dose): Time to attain maximum concentration (tmax)		Days 1-5 (14 times)	No
Primary	PK of fidaxomicin in plasma (single dose): Maximum Concentration (Cmax)		Days 1-5 (14 times)	No
Primary	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)		Days 1-5 (14 times)	No
Primary	PK of fidaxomicin in plasma (single dose): AUC - Time Curve from Time Zero to Infinity (aucinf)		Days 1-5 (14 times)	No
Primary	PK of fidaxomicin in plasma (single dose): AUC - Time Curve from Time Zero to 12 hours (AUC 0-12h)		Days 1-5 (14 times)	No
Primary	PK of fidaxomicin in plasma (single dose): Total Body Clearance after Single Dose (CL/F)		Days 1-5 (14 times)	No
Primary	PK of fidaxomicin in plasma (single dose): Apparent Volume of Distribution During Terminal Phase (Vz/F)		Days 1-5 (14 times)	No
Primary	PK of fidaxomicin in plasma (last dose): Apparent Volume of Distribution During Terminal Phase (Vz/F)		Days 15-17 (11 times)	No
Primary	PK of fidaxomicin in plasma (single dose): Apparent Terminal elimination Half-life (t 1/2)	Single Dose	Days 1-5 (14 times)	No
Primary	PK of fidaxomicin in plasma (last dose): Apparent Terminal elimination Half-life (t 1/2)	Single Dose	Days 15-17 (11 times)	No
Primary	PK of fidaxomicin in plasma (single dose): Trough levels		Days 6, 7, 10, and 12 (pre-morning dose)	No
Primary	PK of fidaxomicin in plasma (last dose): tmax at Steady State (tmax, ss)	Last Dose	Days 15-17 (11 times)	No
Primary	PK of fidaxomicin in plasma (last dose): Cmax at Steady State (Cmax, ss)	Last Dose	Days 15-17 (11 times)	No
Primary	PK of fidaxomicin in plasma (last dose): AUC Over the dosing Interval (AUCtau)		Days 15-17 (11 times)	No
Primary	PK of fidaxomicin in plasma (last dose): CL/F at Steady State (CL/F ss)		Days 15-17 (11 times)	No
Primary	PK of fidaxomicin in plasma (last dose): Peak: Trough Ratio (PTR)		Days 15-17 (11 times)	No
Primary	PK of fidaxomicin in plasma (last dose): Accumulation Ratio (Racc)		Days 15-17 (11 times)	No
Primary	PK of fidaxomicin in plasma (last dose): Pre-dose Plasma Concentration Determined Directly from the Concentration-Time Profile (Ctrough)		Days 15-17 (11 times)	No
Primary	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)		Days 1-5 (6 times)	No
Primary	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 )		Days 1-5 (6 times)	No
Primary	PK of fidaxomicin in urine (single dose): Cumulative Amount of Drug Excreted in the Urine from time Zero to Infinity after Single Dose (Aeinf)		Days 1-5 (6 times)	No
Primary	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)		Days 1-5 (6 times)	No
Primary	PK of fidaxomicin in urine (single dose): Renal Clearance (CL/R		Days 1-5 (6 times)	No
Primary	PK of fidaxomicin in urine (last dose): Cumulative Amount of Drug Excreted in the urine over the dosing Interval at Steady State (Aetau)		Day 15 (1 time)	No
Primary	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)		Day 15 (1 time)	No
Primary	PK of fidaxomicin in urine (last dose): Renal Clearance at Steady State (CLR,ss)		Day 15 ( 1 time)	No
Primary	PK of fidaxomicin in feces (single dose): Amount of Drug Excreted in the Feces (Ae)		Days 1-5 (5 times)	No
Primary	PK of fidaxomicin in feces (last dose): Amount of Drug Excreted in the Feces (Ae)		Days 15-17 (first bowel movement (BM) following the last dose to be collected)	No
Primary	PK of fidaxomicin in feces (single dose): Percent Fraction of Administered Drug Excreted Unchanged in the Feces (%Ae)		Days 1-5 (5 times)	No
Primary	PK of fidaxomicin in feces (last dose): Percent Fraction of Administered Drug Excreted Unchanged in the Feces (%Ae)		Days 15-17 (first BM following the last dose to be collected)	No

External Links

•   Link to Results on JAPIC