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| Name | Class |
|---|---|
| Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Fidaxomicin low dose in Japanese males | Experimental |
| |
| Cohort 2: Fidaxomicin high dose in Japanese males | Experimental |
| |
| Cohort 3: Fidaxomicin high dose in Caucasian males | Experimental |
| |
| Matching Placebo in Caucasian males | Placebo Comparator |
| |
| Matching Placebo in Japanese males | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fidaxomicin | Drug | oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) of fidaxomicin in plasma (single dose): Lag time (tlag) | Days 1-5 (14 times) | |
| PK of fidaxomicin plasma (single dose): Time to attain maximum concentration (tmax) | Days 1-5 (14 times) | |
| PK of fidaxomicin in plasma (single dose): Maximum Concentration (Cmax) | 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) | Days 1-5 (14 times) | |
| PK of fidaxomicin in plasma (single dose): AUC - Time Curve from Time Zero to Infinity (aucinf) | Days 1-5 (14 times) | |
| PK of fidaxomicin in plasma (single dose): AUC - Time Curve from Time Zero to 12 hours (AUC 0-12h) | Days 1-5 (14 times) | |
| PK of fidaxomicin in plasma (single dose): Total Body Clearance after Single Dose (CL/F) | Days 1-5 (14 times) | |
| PK of fidaxomicin in plasma (single dose): Apparent Volume of Distribution During Terminal Phase (Vz/F) | Days 1-5 (14 times) | |
| PK of fidaxomicin in plasma (last dose): Apparent Volume of Distribution During Terminal Phase (Vz/F) | Days 15-17 (11 times) |
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Inclusion Criteria:
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
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
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
The subject is a healthy Caucasian male and has a BMI of 18.0 to 32.0 kg/m2, inclusive
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sr. Medical Director | Astellas Pharma Global Development, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parexel | Glendale | California | 91206 | United States |
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| Placebo | Drug | oral |
|
| PK of fidaxomicin in plasma (single dose): Apparent Terminal elimination Half-life (t 1/2) | Single Dose | Days 1-5 (14 times) |
| PK of fidaxomicin in plasma (last dose): Apparent Terminal elimination Half-life (t 1/2) | Single Dose | Days 15-17 (11 times) |
| PK of fidaxomicin in plasma (single dose): Trough levels | Days 6, 7, 10, and 12 (pre-morning dose) |
| PK of fidaxomicin in plasma (last dose): tmax at Steady State (tmax, ss) | Last Dose | Days 15-17 (11 times) |
| PK of fidaxomicin in plasma (last dose): Cmax at Steady State (Cmax, ss) | Last Dose | Days 15-17 (11 times) |
| PK of fidaxomicin in plasma (last dose): AUC Over the dosing Interval (AUCtau) | Days 15-17 (11 times) |
| PK of fidaxomicin in plasma (last dose): CL/F at Steady State (CL/F ss) | Days 15-17 (11 times) |
| PK of fidaxomicin in plasma (last dose): Peak: Trough Ratio (PTR) | Days 15-17 (11 times) |
| PK of fidaxomicin in plasma (last dose): Accumulation Ratio (Racc) | Days 15-17 (11 times) |
| PK of fidaxomicin in plasma (last dose): Pre-dose Plasma Concentration Determined Directly from the Concentration-Time Profile (Ctrough) | 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) | 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 ) | 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) | 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) | Days 1-5 (6 times) |
| PK of fidaxomicin in urine (single dose): Renal Clearance (CL/R | 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) | 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) | Day 15 (1 time) |
| PK of fidaxomicin in urine (last dose): Renal Clearance at Steady State (CLR,ss) | Day 15 ( 1 time) |
| PK of fidaxomicin in feces (single dose): Amount of Drug Excreted in the Feces (Ae) | Days 1-5 (5 times) |
| 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) |
| PK of fidaxomicin in feces (single dose): Percent Fraction of Administered Drug Excreted Unchanged in the Feces (%Ae) | Days 1-5 (5 times) |
| 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) |
| ID | Term |
|---|---|
| D000077732 | Fidaxomicin |
| C487655 | OPT 80 |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D061065 | Polyketides |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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