Study Of Safety And Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-016)

A 12-Week, Phase 2, Randomized, Double-Blinded, Placebo-Controlled, Dose-Ranging, Parallel Group Study to Evaluate the Safety, Tolerability and Efficacy Of Once Daily PF-04971729 And Sitagliptin On Glycemic Control And Body Weight In Adult Patients With Type 2 Diabetes Mellitus Inadequately Controlled On Metformin

MK-8835-016 (B1521006) is designed to evaluate the safety and efficacy of an investigational drug, ertugliflozin (MK-8835, PF-04971729) in participants with Type 2 diabetes mellitus. Participants in the study will receive 1 of 6 treatments for 12 weeks including 1 treatment with an approved drug (sitagliptin) for the treatment of Type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo to Ertugliflozin; Drug: Placebo to Sitagliptin; Drug: Metformin; Drug: Ertugliflozin 1 mg; Drug: Ertugliflozin 5 mg; Drug: Ertugliflozin 25 mg; Drug: Sitagliptin 100 mg

• Study Type: Interventional
• Enrollment (Actual): 375
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants with type 2 diabetes on stable doses of background medicines for management of the diabetes; aged 18-70 years; body mass index between 23-45 kg/m^2

Exclusion Criteria:

• Participants with type 1 diabetes, heart attack or stroke in last 6-months, uncontrolled blood pressure, significant kidney disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo for ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to sitagliptin, oral, once daily for 84 days	Drug: Placebo to Ertugliflozin; Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days; Drug: Placebo to Sitagliptin; Tablet, matching placebo to 100 mg, once daily for 84 days; Drug: Metformin; Participants continued pre-study stable doses of metformin during the run-in and treatment periods of the study (maximum dose up to 2500 mg/day or 3000 mg/day where the maximum metformin dose per the local country product labels was 3000 mg/day).; Other Names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
Experimental: Ertugliflozin 1 mg; Ertugliflozin 1 mg, placebo for ertugliflozin (1 mg or 5 mg and 25 mg), and placebo to sitagliptin, oral, once daily for 84 days	Drug: Placebo to Ertugliflozin; Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days; Drug: Placebo to Sitagliptin; Tablet, matching placebo to 100 mg, once daily for 84 days; Drug: Metformin; Participants continued pre-study stable doses of metformin during the run-in and treatment periods of the study (maximum dose up to 2500 mg/day or 3000 mg/day where the maximum metformin dose per the local country product labels was 3000 mg/day).; Other Names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®; Drug: Ertugliflozin 1 mg; Tablet, 1 mg, once daily for 84 days
Experimental: Ertugliflozin 5 mg; Ertugliflozin 5 mg, placebo for ertugliflozin (1 mg or 5 mg and 25 mg), and placebo to sitagliptin, oral, once daily for 84 days	Drug: Placebo to Ertugliflozin; Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days; Drug: Placebo to Sitagliptin; Tablet, matching placebo to 100 mg, once daily for 84 days; Drug: Metformin; Participants continued pre-study stable doses of metformin during the run-in and treatment periods of the study (maximum dose up to 2500 mg/day or 3000 mg/day where the maximum metformin dose per the local country product labels was 3000 mg/day).; Other Names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®; Drug: Ertugliflozin 5 mg; Tablet(s), 1 or 2, 5-mg tablets once daily for 84 days
Experimental: Ertugliflozin 10 mg; Ertugliflozin 10 mg, placebo for ertugliflozin (25 mg), and placebo to sitagliptin, oral, once daily for 84 days	Drug: Placebo to Ertugliflozin; Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days; Drug: Placebo to Sitagliptin; Tablet, matching placebo to 100 mg, once daily for 84 days; Drug: Metformin; Participants continued pre-study stable doses of metformin during the run-in and treatment periods of the study (maximum dose up to 2500 mg/day or 3000 mg/day where the maximum metformin dose per the local country product labels was 3000 mg/day).; Other Names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®; Drug: Ertugliflozin 5 mg; Tablet(s), 1 or 2, 5-mg tablets once daily for 84 days
Experimental: Ertugliflozin 25 mg; Ertugliflozin 25 mg, placebo for ertugliflozin (1 mg or 5 mg), and placebo to sitagliptin, oral, once daily for 84 days	Drug: Placebo to Ertugliflozin; Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days; Drug: Placebo to Sitagliptin; Tablet, matching placebo to 100 mg, once daily for 84 days; Drug: Metformin; Participants continued pre-study stable doses of metformin during the run-in and treatment periods of the study (maximum dose up to 2500 mg/day or 3000 mg/day where the maximum metformin dose per the local country product labels was 3000 mg/day).; Other Names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®; Drug: Ertugliflozin 25 mg; Tablet, 25 mg, once daily for 84 days
Active Comparator: Sitagliptin 100 mg; Sitagliptin 100 mg, placebo for ertugliflozin (1 mg or 5 mg and 25 mg), oral, once daily for 84 days	Drug: Placebo to Ertugliflozin; Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days; Drug: Metformin; Participants continued pre-study stable doses of metformin during the run-in and treatment periods of the study (maximum dose up to 2500 mg/day or 3000 mg/day where the maximum metformin dose per the local country product labels was 3000 mg/day).; Other Names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®; Drug: Sitagliptin 100 mg; Tablet, 100 mg, once daily for 84 days; Other Names: Januvia®, Tesavel®, Xelevia®, Ristaben®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Hemoglobin A1c (HbA1c)	HbA1c is measured as percent.	Baseline
Change From Baseline in HbA1c at Week 12	HbA1c is measured as percent. The change from baseline is the Week 12 HbA1c percent minus the Week 0 HbA1c percent (last observation carried forward [LOCF]).	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1C at Week 2	HbA1c is measured as percent. The change from baseline is the Week 2 HbA1c percent minus the Week 0 HbA1c percent (LOCF).	Baseline and Week 2
Change From Baseline in HbA1c at Week 4	HbA1c is measured as percent. The change from baseline is the Week 4 HbA1c percent minus the Week 0 HbA1c percent (LOCF).	Baseline and Week 4
Change From Baseline in HbA1c at Week 8	HbA1c is measured as percent. The change from baseline is the Week 8 HbA1c percent minus the Week 0 HbA1c percent (LOCF).	Baseline and Week 8
Baseline Body Weight		Baseline
Percent Change From Baseline in Body Weight at Week 12	The percent change from baseline is the ([Week 12 body weight minus the Week 0 body weight] divided by the Week 0 body weight) X 100 (LOCF).	Baseline and Week 12
Percent Change From Baseline in Body Weight at Week 2	The percent change from baseline is the ([Week 2 body weight minus the Week 0 body weight] divided by the Week 0 body weight) X 100 (LOCF).	Baseline and Week 2
Percent Change From Baseline in Body Weight at Week 4	The percent change from baseline is the ([Week 4 body weight minus the Week 0 body weight] divided by the Week 0 body weight) X 100 (LOCF).	Baseline and Week 4
Percent Change From Baseline in Body Weight at Week 8	The percent change from baseline is the ([Week 8 body weight minus the Week 0 body weight] divided by the Week 0 body weight) X 100 (LOCF).	Baseline and Week 8
Baseline Systolic Blood Pressure	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed.	Baseline
Change From Baseline in Systolic Blood Pressure at Week 12	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 12 systolic blood pressure minus the Week 0 systolic blood pressure (LOCF).	Baseline and Week 12
Change From Baseline in Systolic Blood Pressure at Week 2	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 2 systolic blood pressure minus the Week 0 systolic blood pressure (LOCF).	Baseline and Week 2
Change From Baseline in Systolic Blood Pressure at Week 4	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 4 systolic blood pressure minus the Week 0 systolic blood pressure (LOCF).	Baseline and Week 4
Change From Baseline in Systolic Blood Pressure at Week 8	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 8 systolic blood pressure minus the Week 0 systolic blood pressure (LOCF).	Baseline and Week 8
Baseline Diastolic Blood Pressure	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed.	Baseline
Change From Baseline in Diastolic Blood Pressure at Week 12	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 12 diastolic blood pressure minus the Week 0 diastolic blood pressure (LOCF).	Baseline and Week 12
Change From Baseline in Diastolic Blood Pressure at Week 2	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 2 diastolic blood pressure minus the Week 0 diastolic blood pressure (LOCF).	Baseline and Week 2
Change From Baseline in Diastolic Blood Pressure at Week 4	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 4 diastolic blood pressure minus the Week 0 diastolic blood pressure (LOCF).	Baseline and Week 4
Change From Baseline in Diastolic Blood Pressure at Week 8	Sitting blood pressure was measured in triplicate and the average of the measurements taken at a single assessment time was analyzed. The change from baseline is the Week 8 diastolic blood pressure minus the Week 0 diastolic blood pressure (LOCF).	Baseline and Week 8
Baseline Fasting Plasma Glucose	Laboratory measurements were performed after an overnight fast ≥8 hours in duration.	Baseline
Change From Baseline in Fasting Plasma Glucose at Week 12	The change from baseline is the Week 12 FPG minus the Week 0 fasting plasma glucose (LOCF). Laboratory measurements were performed after an overnight fast ≥8 hours in duration.	Baseline and Week 12
Change From Baseline in Fasting Plasma Glucose at Week 2	The change from baseline is the Week 2 FPG minus the Week 0 FPG (LOCF). Laboratory measurements were performed after an overnight fast ≥8 hours in duration.	Baseline and Week 2
Change From Baseline in Fasting Plasma Glucose at Week 4	The change from baseline is the Week 4 FPG minus the Week 0 FPG (LOCF). Laboratory measurements were performed after an overnight fast ≥8 hours in duration.	Baseline and Week 4
Change From Baseline in Fasting Plasma Glucose at Week 8	The change from baseline is the Week 8 FPG minus the Week 0 FPG (LOCF). Laboratory measurements were performed after an overnight fast ≥8 hours in duration.	Baseline and Week 8
Percentage of Participants Achieving HbA1c <7% at Week 12	Laboratory measurements were performed after an overnight fast ≥8 hours in duration.	Week 12
Percentage of Participants Achieving HbA1C <6.5% at Week 12	Laboratory measurements were performed after an overnight fast ≥8 hours in duration.	Week 12
Number of Participants Who Experienced an Advere Event (AE)	An adverse event is defines as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Below table includes all data collected since the first dose of sponsor-provided metformin.	Up to 98 days
Number of Participants Who Discontinued Study Medication Due to an AE	An adverse event is defines as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Below table includes all data collected since the first dose of sponsor-provided metformin and excludes a temporary discontinuation of study medication.	Up to 84 days

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.
• Amin NB, Wang X, Jain SM, Lee DS, Nucci G, Rusnak JM. Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin. Diabetes Obes Metab. 2015 Jun;17(6):591-598. doi: 10.1111/dom.12460. Epub 2015 Mar 31.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2010
• Primary Completion (Actual): January 20, 2011
• Study Completion (Actual): January 20, 2011

Study Registration Dates

• First Submitted: January 29, 2010
• First Submitted That Met QC Criteria: January 29, 2010
• First Posted (Estimate): February 1, 2010

Study Record Updates

• Last Update Posted (Actual): September 13, 2018
• Last Update Submitted That Met QC Criteria: August 15, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; Phase 2; safety and efficacy study with ertugliflozin (PF-04971729, MK-8835)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate; Ertugliflozin
• Other Study ID Numbers: 8835-016; B1521006 (Other Identifier: Pfizer protocol number); 2009-017131-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No