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

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

Official Title
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A Phase 1, Randomized, Placebo-Controlled, Parallel Group, 14 Day Repeated Dose Escalation Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of PF-04971729 In Otherwise Healthy Overweight And Obese Adult Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: Ertugliflozin
* Drug: Placebo to Ertugliflozin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ertugliflozin 1 mg<br>Ertugliflozin 1 mg, oral, once daily for 14 days | Drug: Ertugliflozin<br>* Ertugliflozin oral dosing 1 mg, 5 mg, 25 mg, or 100 mg solutions/suspensions administered once daily for 14 days immediately after breakfast<br>* Other names: MK-8835;|
| Experimental: Ertugliflozin up to 5 mg<br>Ertugliflozin up to 5 mg, oral, once daily for 14 days | Drug: Ertugliflozin<br>* Ertugliflozin oral dosing 1 mg, 5 mg, 25 mg, or 100 mg solutions/suspensions administered once daily for 14 days immediately after breakfast<br>* Other names: MK-8835;|
| Experimental: Ertugliflozin up to 25 mg<br>Ertugliflozin up to 25 mg, oral, once daily for 14 days | Drug: Ertugliflozin<br>* Ertugliflozin oral dosing 1 mg, 5 mg, 25 mg, or 100 mg solutions/suspensions administered once daily for 14 days immediately after breakfast<br>* Other names: MK-8835;|
| Experimental: Ertugliflozin up to 100 mg<br>Ertugliflozin up to 100 mg, once daily for 14 days | Drug: Ertugliflozin<br>* Ertugliflozin oral dosing 1 mg, 5 mg, 25 mg, or 100 mg solutions/suspensions administered once daily for 14 days immediately after breakfast<br>* Other names: MK-8835;|
| Placebo Comparator: Placebo<br>Placebo to Ertugliflozin once daily for 14 days | Drug: Placebo to Ertugliflozin<br>* Placebo oral dosing solutions/suspensions administered once daily for 14 days immediately after breakfast<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing an Adverse Event (AE) |  | Up to 28 days postdose (Up to 42 days) | 
| Number of Participants Discontinuing Study Drug Due to an AE |  | Up to 14 days | 
| Area under the plasma concentration-time curve (AUC) over the dosing interval tau (AUCtau) for ertugliflozin |  | Up to 17 days | 
| Maximum plasma concentration (Cmax) of ertugliflozin |  | Up to 17 days | 
| Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin |  | Up to 17 days | 
| Ertugliflozin half life (t1/2) |  | Up to 17 Days | 
| Apparent clearance (CL/F) after a single dose of ertugliflozin |  | Up to 17 days | 
| Apparent volume of distribution (Vz/F) |  | Up to 17 days | 
| Observed Accumulation Ratio of Area Under the Curve for the dosing interval of ertugliflozin (Rac[obs]) |  | Up to 17 days | 
| Change from baseline in 24-hour weighted mean glucose |  | Baseline and Day 14 | 
| Change from baseline in 24-hour urinary glucose excretion |  | Baseline and Day 14 | 
| Change from baseline in 24-hour plasma C-peptide |  | Baseline and Day 14 | 
| Inhibition of glucose reabsorption |  | Baseline and Day 14 | 
| Change from baseline in body weight |  | Baseline and Day 14 | 
| Area under the plasma concentration-time curve over 8 hours (AUC[0-8]) for serum intact parathyroid hormone |  | Up to 17 days | 
| Area under the plasma concentration-time curve over 24 hours (AUC[0-24]) for serum intact parathyroid hormone |  | Up to 17 days | 
| Trough concentration of serum intact parathyroid hormone (Ctrough) |  | Up to 17 days |