A Phase 1, Randomized, Double Blind, Placebo-Controlled, Parallel Cohort, Single Dose Escalation And Multiple Dose Study In Japanese Healthy Subjects, And Open Label, Single Dose Escalation Study In Western Healthy Subjects To Investigate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of PF-04971729
Overview
- Phase
- Phase 1
- Intervention
- Ertugliflozin
- Conditions
- Diabetes Mellitus, Type 2
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 24
- Primary Endpoint
- AUClast for ertugliflozin for the Multiple Dose Cohort
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This study is to characterize the pharmacokinetics, safety, tolerability, and pharmacodynamics of single and multiple oral doses (SD, MD) of ertugliflozin (PF-04971729, MK-8835) in Japanese healthy participants. The secondary objective is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of ertugliflozin in Western healthy participants as compared to Japanese healthy participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male and/or female subjects of non-childbearing potential, between the ages of 18 and 55 years, inclusive
- •Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs).
- •Japanese subjects must have four Japanese grandparents who were born in Japan.
- •Mean body weight and the body weight range of Western subjects are similar to those of Japanese subjects with a 10% plus and minus error.
- •An informed consent document signed and dated by the subject.
- •Subjects who are willing and able to comply with scheduled visits, treatment plan,laboratory tests, and other study procedures.
Exclusion Criteria
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
- •Asian or Polynesian subjects in Western subject groups.
- •Any condition possibly affecting drug absorption (eg, gastrectomy).
- •A positive urine drug screen.
- •History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males within 6 months of screening.
- •History or evidence of habitual use of tobacco or nicotine containing products within 3 months of Screening, with the exception of light smoking (up to 5 cigarettes per day or the equivalent).
- •Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study medication.
- •12-lead ECG demonstrating QTc \>450 msec at screening.
- •Subjects with ANY of the following abnormalities on safety laboratory tests):
- •Evidence of glycosuria, as defined by a positive urine dipstick test;
Arms & Interventions
Single Dose Japanese Cohort
This will be a single dose Cohort in which Japanese healthy participants will receive 3 ascending single doses (1 mg, 5 mg, and 25 mg) of ertugliflozin or placebo through 3 dosing periods. A minimum wash out period of 7-days will be set between each dose administration.
Intervention: Ertugliflozin
Single Dose Japanese Cohort
This will be a single dose Cohort in which Japanese healthy participants will receive 3 ascending single doses (1 mg, 5 mg, and 25 mg) of ertugliflozin or placebo through 3 dosing periods. A minimum wash out period of 7-days will be set between each dose administration.
Intervention: Placebo
Single dose Western cohort
This will be a single dose Cohort in which Western healthy participants will receive 3 ascending single doses (1 mg, 5 mg, and 25 mg) of ertugliflozin through 3 dosing periods. A minimum wash out period of 7-days will be set between each dose administration.
Intervention: Ertugliflozin
Multiple Dose Japanese Cohort
This will be a multiple dose Cohort in which Japanese healthy participants will receive once-daily 25 mg ertugliflozin or placebo for 7 days.
Intervention: Ertugliflozin
Multiple Dose Japanese Cohort
This will be a multiple dose Cohort in which Japanese healthy participants will receive once-daily 25 mg ertugliflozin or placebo for 7 days.
Intervention: Placebo
Outcomes
Primary Outcomes
AUClast for ertugliflozin for the Multiple Dose Cohort
Time Frame: Up to Day 10
AUCinf for ertugliflozin for the Multiple Dose Cohort
Time Frame: Up to Day 10
t1/2 for the Multiple Dose Cohort
Time Frame: Up to Day 10
CL/F of ertugliflozin for the Multiple Dose Cohort
Time Frame: Up to Day 10
Vz/F for the Multiple Dose Cohort
Time Frame: Up to Day 10
Urinary Glucose Excretion over 24 hours for the Single Dose Cohort
Time Frame: Up to 24 hours postdose (Up to Day 2)
Cmax of ertugliflozin for the Multiple Dose Cohort
Time Frame: Up to Day 10
Tmax of ertugliflozin for the Multiple Dose Cohort
Time Frame: Up to Day 10
Maximum plasma concentration (Cmax) of ertugliflozin for the Single Dose Cohort
Time Frame: Up to Day 4 of each treatment period
Rac for the Single Dose Cohort
Time Frame: Up to Day 10
Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin for the Single Dose Cohort
Time Frame: Up to Day 4 of each treatment period
Area under the plasma concentration-time curve (AUC) from time 0 to time of the last quantifiable concentration (AUClast) for ertugliflozin for the Single Dose Cohort
Time Frame: Up to Day 4 of each treatment period
AUC from Hour 0 to infinity (AUCinf) for ertugliflozin for the Single Dose Cohort
Time Frame: Up to Day 4 of each treatment period
Ertugliflozin half life (t1/2) for the Single Dose Cohort
Time Frame: Up to Day 4 of each treatment period
Apparent clearance (CL/F) of ertugliflozin for the Single Dose Cohort
Time Frame: Up to Day 4 of each treatment period
Apparent volume of distribution (Vz/F) for the Single Dose Cohort
Time Frame: Up to Day 4 of each treatment period
Accumulation Ratio of Area Under the Curve for the dosing interval of ertugliflozin (Rac) for the Single Dose Cohort
Time Frame: Up to Day 4 of each treatment period
Number of participants who experienced an adverse event (AE) for the Single Dose Cohort
Time Frame: Up to 10 days after the final dose of study drug (Up to Day 11)
Number of participants who discontinued study drug due to an AE for the Single Dose Cohort
Time Frame: Up to Day 1 of each treatment period
Number of participants who experienced an AE for the Multiple Dose Cohort
Time Frame: Up to 10 days after the final dose of study drug (Up to Day 17)
Number of participants who discontinued study drug due to an AE for the Multiple Dose Cohort
Time Frame: Up to Day 7
Urinary Glucose Excretion over 24 hours for the Multiple Dose Cohort
Time Frame: Up to 24 hours postdose (Up to Day 8)