Study To Estimate The Relative Bioavailability of Ertugliflozin (PF-04971729, MK-8835) in Healthy Adult Participants (MK-8835-039)

A Phase 1, Cross-Over, Single-Dose, Open-Label Study To Estimate The Relative Bioavailability Of Three Different Formulations Of PF-04971729 in Lean To Obese, Otherwise Healthy Adult Subjects

The purpose of this study is to examine the rate and extent of absorption of three oral formulations of ertugliflozin (PF 04971729, MK-8835) administered in lean to obese healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ertugliflozin 10 mg tablet; Drug: Ertugliflozin OC Fast; Drug: Ertugliflozin OC Slow

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and/or female subjects between the ages of 21 and 65 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests). Women must be of non childbearing potential
• Body Mass Index (BMI) of 18.5 to 35.4 kg/m2; and a total body weight >50 kg (110 lbs).
• 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 (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of screening).
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• A positive urine drug screen at Screening or prior to dosing in Period 1.
• History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ertugliflozin 10 mg: tablet→osmotic capsule (OC) fast→OC slow; The three treatments are A) a single dose of 10 mg administered as 2x5 mg material sparing formulation tablets B) a single dose of 10 mg extemporaneously prepared osmotic capsule with target release rate of approximately 6 hours (EP-Osmotic Capsule-Fast) and C) a single dose of 10 mg extemporaneously prepared osmotic capsule with target release rate of approximately 14 hours (EP-Osmotic Capsule-Slow). Treatment are administered on Day 1, Hour 0 of each dosing period with a minimum of 7-days wash-out between treatments A, B, and C.	Drug: Ertugliflozin 10 mg tablet; A single dose of 10 mg ertugliflozin administered as 2x5 mg material sparing formulation tablets.; Drug: Ertugliflozin OC Fast; Formulation B) Ertugliflozin 10 mg OC Fast; Drug: Ertugliflozin OC Slow; Formulation C) Ertugliflozin 10 mg OC Slow
Experimental: Ertugliflozin 10 mg: tablet→OC slow→OC fast; The three treatments are A) a single dose of 10 mg administered as 2x5 mg material sparing formulation tablets B) a single dose of 10 mg EP-Osmotic Capsule-Fast and C) a single dose of 10 mg EP-Osmotic Capsule-Slow. Treatment are administered on Day 1, Hour 0 of each dosing period with a minimum of 7-days wash-out between treatments A, B, and C.	Drug: Ertugliflozin 10 mg tablet; A single dose of 10 mg ertugliflozin administered as 2x5 mg material sparing formulation tablets.; Drug: Ertugliflozin OC Fast; Formulation B) Ertugliflozin 10 mg OC Fast; Drug: Ertugliflozin OC Slow; Formulation C) Ertugliflozin 10 mg OC Slow
Experimental: Ertugliflozin 10 mg: OC fast→tablet→OC slow; The three treatments are A) a single dose of 10 mg administered as 2x5 mg material sparing formulation tablets B) a single dose of 10 mg EP-Osmotic Capsule-Fast and C) a single dose of 10 mg EP-Osmotic Capsule-Slow. Treatment are administered on Day 1, Hour 0 of each dosing period with a minimum of 7-days wash-out between treatments A, B, and C.	Drug: Ertugliflozin 10 mg tablet; A single dose of 10 mg ertugliflozin administered as 2x5 mg material sparing formulation tablets.; Drug: Ertugliflozin OC Fast; Formulation B) Ertugliflozin 10 mg OC Fast; Drug: Ertugliflozin OC Slow; Formulation C) Ertugliflozin 10 mg OC Slow
Experimental: Ertugliflozin 10 mg: OC fast→OC slow→tablet; The three treatments are A) a single dose of 10 mg administered as 2x5 mg material sparing formulation tablets B) a single dose of 10 mg EP-Osmotic Capsule-Fast and C) a single dose of 10 mg EP-Osmotic Capsule-Slow. Treatment are administered on Day 1, Hour 0 of each dosing period with a minimum of 7-days wash-out between treatments A, B, and C.	Drug: Ertugliflozin 10 mg tablet; A single dose of 10 mg ertugliflozin administered as 2x5 mg material sparing formulation tablets.; Drug: Ertugliflozin OC Fast; Formulation B) Ertugliflozin 10 mg OC Fast; Drug: Ertugliflozin OC Slow; Formulation C) Ertugliflozin 10 mg OC Slow
Experimental: Ertugliflozin 10 mg: OC slow→tablet→OC fast; The three treatments are A) a single dose of 10 mg administered as 2x5 mg material sparing formulation tablets B) a single dose of 10 mg EP-Osmotic Capsule-Fast and C) a single dose of 10 mg EP-Osmotic Capsule-Slow. Treatment are administered on Day 1, Hour 0 of each dosing period with a minimum of 7-days wash-out between treatments A, B, and C.	Drug: Ertugliflozin 10 mg tablet; A single dose of 10 mg ertugliflozin administered as 2x5 mg material sparing formulation tablets.; Drug: Ertugliflozin OC Fast; Formulation B) Ertugliflozin 10 mg OC Fast; Drug: Ertugliflozin OC Slow; Formulation C) Ertugliflozin 10 mg OC Slow
Experimental: Ertugliflozin 10 mg: OC slow→OC fast→tablet; The three treatments are A) a single dose of 10 mg administered as 2x5 mg material sparing formulation tablets B) a single dose of 10 mg EP-Osmotic Capsule-Fast and C) a single dose of 10 mg EP-Osmotic Capsule-Slow. Treatment are administered on Day 1, Hour 0 of each dosing period with a minimum of 7-days wash-out between treatments A, B, and C.	Drug: Ertugliflozin 10 mg tablet; A single dose of 10 mg ertugliflozin administered as 2x5 mg material sparing formulation tablets.; Drug: Ertugliflozin OC Fast; Formulation B) Ertugliflozin 10 mg OC Fast; Drug: Ertugliflozin OC Slow; Formulation C) Ertugliflozin 10 mg OC Slow

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration-time curve (AUC) from time 0 to time of the last quantifiable concentration (AUClast) for ertugliflozin	Up to 48 hr. postdose (Up to Day 3 in each dosing period)
AUC from Hour 0 to infinity (AUCinf) for ertugliflozin	Up to 48 hr. postdose (Up to Day 3 in each dosing period)
Maximum plasma concentration (Cmax) of ertugliflozin	Up to 48 hr. postdose (Up to Day 3 in each dosing period)
Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin	Up to 48 hr. postdose (Up to Day 3 in each dosing period)
Ertugliflozin half life (t1/2)	Up to 48 hr. postdose (Up to Day 3 in each dosing period)
Number of Participants Experiencing an Adverse Event (AE)	Up to 28 days postdose (Up to 49 days)
Number of Participants Discontinuing Study Drug Due to an AE	Up to Day 21
Urinary glucose excretion	Up to 48 hr. postdose (Up to Day 3 in each dosing period)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Pfizer

Publications and helpful links

General Publications

• Marshall JC, Liang Y, Sahasrabudhe V, Tensfeldt T, Fediuk DJ, Zhou S, Krishna R, Dawra VK, Wood LS, Sweeney K. Meta-Analysis of Noncompartmental Pharmacokinetic Parameters of Ertugliflozin to Evaluate Dose Proportionality and UGT1A9 Polymorphism Effect on Exposure. J Clin Pharmacol. 2021 Sep;61(9):1220-1231. doi: 10.1002/jcph.1866. Epub 2021 Jun 19.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: April 27, 2010
• First Submitted That Met QC Criteria: April 29, 2010
• First Posted (Estimate): May 3, 2010

Study Record Updates

• Last Update Posted (Estimate): March 17, 2016
• Last Update Submitted That Met QC Criteria: March 16, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; Relative Bioavailability
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Ertugliflozin
• Other Study ID Numbers: 8835-039