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A Multiple Dose Study Of Ertugliflozin (PF-04971729, MK-8835) In Otherwise Healthy Overweight And Obese Volunteers (MK-8835-037)

Phase 1
Completed
Conditions
Healthy Volunteer
Interventions
Registration Number
NCT01018823
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

Ertugliflozin (PF-04971729, MK-8835) is under development for the treatment of Type 2 Diabetes. The primary purpose of this trial is to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, of multiple oral doses of ertugliflozin.

Detailed Description

To evaluate the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics, of multiple oral doses of ertugliflozin.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
Inclusion Criteria

Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive.

Body Mass Index (BMI) of 26.5 to 35.5 kg/m2; and a total body weight >50 kg (110 lbs).

Exclusion Criteria

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).

Evidence of glycosuria, as defined by a positive urine dipstick test; Fasting (at least 10 hours) serum triglyceride >300 mg/dL; Fasting (at least 10 hours) LDL-cholesterol >190 mg/dL; Fasting (at least 10 hours) serum 25-OH Vitamin D concentration <20 ng/mL

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo to ErtugliflozinPlacebo to Ertugliflozin once daily for 14 days
Ertugliflozin 1 mgErtugliflozinErtugliflozin 1 mg, oral, once daily for 14 days
Ertugliflozin up to 5 mgErtugliflozinErtugliflozin up to 5 mg, oral, once daily for 14 days
Ertugliflozin up to 25 mgErtugliflozinErtugliflozin up to 25 mg, oral, once daily for 14 days
Ertugliflozin up to 100 mgErtugliflozinErtugliflozin up to 100 mg, once daily for 14 days
Primary Outcome Measures
NameTimeMethod
Change from baseline in 24-hour urinary glucose excretionBaseline and Day 14
Change from baseline in 24-hour plasma C-peptideBaseline and Day 14
Area under the plasma concentration-time curve over 8 hours (AUC[0-8]) for serum intact parathyroid hormoneUp to 17 days
Trough concentration of serum intact parathyroid hormone (Ctrough)Up to 17 days
Area under the plasma concentration-time curve over 24 hours (AUC[0-24]) for serum intact parathyroid hormoneUp to 17 days
Number of Participants Discontinuing Study Drug Due to an AEUp to 14 days
Maximum plasma concentration (Cmax) of ertugliflozinUp to 17 days
Ertugliflozin half life (t1/2)Up to 17 Days
Observed Accumulation Ratio of Area Under the Curve for the dosing interval of ertugliflozin (Rac[obs])Up to 17 days
Area under the plasma concentration-time curve (AUC) over the dosing interval tau (AUCtau) for ertugliflozinUp to 17 days
Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozinUp to 17 days
Change from baseline in 24-hour weighted mean glucoseBaseline and Day 14
Change from baseline in body weightBaseline and Day 14
Apparent clearance (CL/F) after a single dose of ertugliflozinUp to 17 days
Apparent volume of distribution (Vz/F)Up to 17 days
Inhibition of glucose reabsorptionBaseline and Day 14
Number of Participants Experiencing an Adverse Event (AE)Up to 28 days postdose (Up to 42 days)
Secondary Outcome Measures
NameTimeMethod
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