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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo to Ertugliflozin
* Drug: Ertugliflozin 1 mg
* Drug: Ertugliflozin 5 mg
* Drug: Ertugliflozin 25 mg
* Drug: Sitagliptin 100 mg
* Drug: Placebo to Sitagliptin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days<br>Drug: Placebo to Sitagliptin<br>* Tablet, matching placebo to 100 mg, once daily for 84 days<br>Drug: Metformin<br>* 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).<br>* Other names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®;|
| Experimental: Ertugliflozin 1 mg<br>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<br>* Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days<br>Drug: Ertugliflozin 1 mg<br>* Tablet, 1 mg, once daily for 84 days<br>Drug: Placebo to Sitagliptin<br>* Tablet, matching placebo to 100 mg, once daily for 84 days<br>Drug: Metformin<br>* 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).<br>* Other names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®;|
| Experimental: Ertugliflozin 5 mg<br>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<br>* Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days<br>Drug: Ertugliflozin 5 mg<br>* Tablet(s), 1 or 2, 5-mg tablets once daily for 84 days<br>Drug: Placebo to Sitagliptin<br>* Tablet, matching placebo to 100 mg, once daily for 84 days<br>Drug: Metformin<br>* 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).<br>* Other names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®;|
| Experimental: Ertugliflozin 10 mg<br>Ertugliflozin 10 mg, placebo for ertugliflozin (25 mg), and placebo to sitagliptin, oral, once daily for 84 days | Drug: Placebo to Ertugliflozin<br>* Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days<br>Drug: Ertugliflozin 5 mg<br>* Tablet(s), 1 or 2, 5-mg tablets once daily for 84 days<br>Drug: Placebo to Sitagliptin<br>* Tablet, matching placebo to 100 mg, once daily for 84 days<br>Drug: Metformin<br>* 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).<br>* Other names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®;|
| Experimental: Ertugliflozin 25 mg<br>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<br>* Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days<br>Drug: Ertugliflozin 25 mg<br>* Tablet, 25 mg, once daily for 84 days<br>Drug: Placebo to Sitagliptin<br>* Tablet, matching placebo to 100 mg, once daily for 84 days<br>Drug: Metformin<br>* 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).<br>* Other names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®;|
| Active Comparator: Sitagliptin 100 mg<br>Sitagliptin 100 mg, placebo for ertugliflozin (1 mg or 5 mg and 25 mg), oral, once daily for 84 days | Drug: Placebo to Ertugliflozin<br>* Tablet(s), 1 or 2, matching placebo to 1-mg, 5-mg and/or 25-mg tablets, once daily for 84 days<br>Drug: Sitagliptin 100 mg<br>* Tablet, 100 mg, once daily for 84 days<br>* Other names: Januvia®, Tesavel®, Xelevia®, Ristaben®;Drug: Metformin<br>* 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).<br>* Other names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 2, safety and efficacy study with ertugliflozin (PF-04971729, MK-8835), Type 2 diabetes mellitus