Study of Safety and Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes And Hypertension (MK-8835-042)

Study Overview
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Brief Summary
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MK-8835-042 (B1521004) is designed to assess the safety and efficacy of an investigational drug, ertugliflozin (MK-8835, PF-04971729), in participants with type 2 diabetes and hypertension. Participants in the study will receive 1 of 5 treatments for 28 days (either placebo, 1 of 3 doses of ertugliflozin [1, 5, or 25 mg], or the approved drug hydrochlorothiazide [HCTZ]). The primary hypothesis of the study was that ertugliflozin was superior to placebo on the change from baseline in average, 24-hour systolic blood pressure (SBP) on Day 28.

Official Title
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A 4-Week, Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel Group Study To Evaluate The Safety, Tolerability And Efficacy Of Once Daily PF-04971729 And Hydrochlorothiazide In Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic And Blood Pressure Control

Conditions
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Diabetes Mellitus, Type 2, Hypertension

Intervention / Treatment
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* Drug: Placebo to Ertuglilflozin 1 or 5 mg
* Drug: Ertugliflozin 1 mg
* Drug: Ertugliflozin 5 mg
* Drug: Ertugliflozin 25 mg
* Drug: HCTZ 12.5mg
* Drug: Placebo to HCTZ
* Drug: Placebo to ertuglilflozin 25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with type 2 diabetes and hypertension Medically stable On at least 1 (and up to 2) oral diabetes drugs And up to 2 medicines for blood pressure control Exclusion Criteria: Participants with type 1 diabetes Heart attack Stroke Uncontrolled blood pressure Significant kidney disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 to ertugliflozin (resembling either 1 mg or 5 mg), placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days. | Drug: Placebo to Ertuglilflozin 1 or 5 mg<br>* Placebo to ertuglilflozin tablet 1 or 5 mg once daily for 28 days<br>Drug: Placebo to HCTZ<br>* Placebo to HCTZ 12.5 mg capsule once daily for 28 days<br>Drug: Placebo to ertuglilflozin 25 mg<br>* Placebo to ertuglilflozin tablet 25 mg once daily for 28 days<br>|
| Experimental: Ertugliflozin 1 mg<br>Ertugliflozin 1 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days | Drug: Ertugliflozin 1 mg<br>* Ertugliflozin tablet 1 mg once daily for 28 days<br>Drug: Placebo to HCTZ<br>* Placebo to HCTZ 12.5 mg capsule once daily for 28 days<br>Drug: Placebo to ertuglilflozin 25 mg<br>* Placebo to ertuglilflozin tablet 25 mg once daily for 28 days<br>|
| Experimental: Ertugliflozin 5 mg<br>Ertugliflozin 5 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days | Drug: Ertugliflozin 5 mg<br>* Ertugliflozin tablet 5 mg once daily for 28 days<br>Drug: Placebo to HCTZ<br>* Placebo to HCTZ 12.5 mg capsule once daily for 28 days<br>Drug: Placebo to ertuglilflozin 25 mg<br>* Placebo to ertuglilflozin tablet 25 mg once daily for 28 days<br>|
| Experimental: Ertugliflozin 25 mg<br>Ertugliflozin 25 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to HCTZ once daily for 28 days | Drug: Placebo to Ertuglilflozin 1 or 5 mg<br>* Placebo to ertuglilflozin tablet 1 or 5 mg once daily for 28 days<br>Drug: Ertugliflozin 25 mg<br>* Ertugliflozin tablet 25 mg once daily for 28 days<br>Drug: Placebo to HCTZ<br>* Placebo to HCTZ 12.5 mg capsule once daily for 28 days<br>|
| Active Comparator: HCTZ 12.5mg<br>HCTZ 12.5 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to ertugliflozin (resembling 25 mg) once daily for 28 days | Drug: Placebo to Ertuglilflozin 1 or 5 mg<br>* Placebo to ertuglilflozin tablet 1 or 5 mg once daily for 28 days<br>Drug: HCTZ 12.5mg<br>* Hydrocholorthiazide (HCTZ) 12.5 mg capsule once daily for 28 days<br>Drug: Placebo to ertuglilflozin 25 mg<br>* Placebo to ertuglilflozin tablet 25 mg once daily for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline 24-hour Average Systolic Blood Pressure (SBP) | Baseline 24-hour average SBP was assessed using 24-hour ambulatory blood pressure monitoring (ABPM). | 24 hours | 
| Change From Baseline on 24-hour Average SBP at Week 4 | Change from baseline on 24-hour average SBP at Week 4 assessed using 24-hour ABPM. In the case of missing data, last observation carried forward (LOCF). | Baseline and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Average Daytime and Nighttime SBP | Daytime was defined as 0600 to 2159 hours, inclusive, local time. Nighttime was defined as 2200 to 0559 hours, inclusive, local time. | Daytime: 16 hours; Nighttime: 8 hours | 
| Change From Baseline on Daytime Average SBP at Week 4 | Change from baseline on daytime average SBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Daytime was defined as 0600 to 2159 hours, inclusive, local time. | Baseline and Week 4 | 
| Change From Baseline on Nighttime Average SBP at Week 4 | Change from baseline on nighttime average SBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Nighttime was defined as 2200 to 0559 hours, inclusive, local time. | Baseline and Week 4 | 
| Baseline Seated, Triplicate Trough SBP | Trough SBP was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the blood pressure measure is obtained. Three measurements of blood pressure were taken at least 2-minutes apart. Baseline trough SBP is calculated as the mean of triplicate (3) trough SBP measures. | Baseline | 
| Change From Baseline in Seated, Triplicate Trough SBP at Week 4 | Trough SBP was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the blood pressure measure is obtained. Three measurements of blood pressure were taken at least 2-minutes apart. The change from baseline at Week 4 is the difference between the baseline and Week 4 assessments. | Baseline and Week 4 | 
| Baseline 24-hour, Daytime and Nightime Average Diastolic Blood Pressure (DBP) | Baseline 24-hour average DBP was assessed using 24-hour ABPM. Daytime was defined as 0600 to 2159 hours, inclusive, local time. Nighttime was defined as 2200 to 0559 hours, inclusive, local time. | up to 24 hours | 
| Change From Baseline on 24-hour Average DBP at Week 4 | Change from baseline on 24-hour average DBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. | Baseline and Week 4 | 
| Change From Baseline on Daytime Average DBP at Week 4 | Change from baseline on daytime average DBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Daytime was defined as 0600 to 2159 hours, inclusive, local time. | Baseline and Week 4 | 
| Change From Baseline on Nighttime Average DBP at Week 4 | Change from baseline on nighttime average DBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Nighttime was defined as 2200 to 0559 hours, inclusive, local time. | Baseline and Week 4 | 
| Baseline Seated, Triplicate Trough DBP | Trough DBP was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the blood pressure measure is obtained. Three measurements of blood pressure were taken at least 2-minutes apart. Baseline trough DBP is calculated as the mean of triplicate (3) trough DBP measures. | Baseline | 
| Change From Baseline in Seated, Triplicate Trough DBP at Week 4 | Trough DBP was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the blood pressure measure is obtained. Three measurements of blood pressure were taken at least 2-minutes apart. The change from baseline at Week 4 is the difference between the baseline and Week 4 assessments. | Baseline and Week 4 | 
| Baseline 24-hour, Daytime and Nightime Average Heart Rate | Baseline 24-hour average heart rate was assessed using 24-hour ABPM. Daytime was defined as 0600 to 2159 hours, inclusive, local time. Nighttime was defined as 2200 to 0559 hours, inclusive, local time. | up to 24 hours | 
| Change From Baseline on 24-hour Average Heart Rate at Week 4 | Change from baseline in 24-hour average heart rate at Week 4 using 24 hour ABPM. | Baseline and Week 4 | 
| Change From Baseline on Daytime Average Heart Rate at Week 4 | Change from baseline in daytime average heart rate at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Daytime was defined as 0600 to 2159 hours, inclusive, local time. | Baseline and Week 4 | 
| Change From Baseline on Nighttime Average Heart Rate at Week 4 | Change from baseline in 24-hour nighttime average heart rate at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Nighttime was defined as 2200 to 0559 hours, inclusive, local time. | Baseline and Week 4 | 
| Baseline Seated, Triplicate Trough Heart Rate | Trough heart rate was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the heart rate measure was obtained. Three measurements of heart rate were taken at least 2-minutes apart. Baseline trough heart rate is calculated as the mean of triplicate (3) trough heart rate measures. | Baseline | 
| Change From Baseline in Seated, Triplicate Trough Heart Rate at Week 4 | Trough heart rate was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the heart rate measure was obtained. Three measurements of heart rate were taken at least 2-minutes apart. The change from baseline at Week 4 is the difference between the baseline and Week 4 assessments. | Baseline and Week 4 | 
| Baseline 24-hour Average Urinary Glucose Excretion | Urinary glucose excetion was corrected for a duration of 24 hours (with appropriate duration of collection defined as >20 hours and <28 hours). | 24 hours | 
| Change From Baseline on 24-hour Urinary Glucose Excretion at Week 4 | Urinary glucose excetion was corrected for a duration of 24 hours (with appropriate duration of collection defined as >20 hours and <28 hours). In the case of missing data, LOCF. | Baseline and Week 4 | 
| Baseline Fasting Plasma Glucose (FPG) | For FPG, blood was drawn after an overnight fast of at least 8 hours (except water). | Baseline | 
| Change From Baseline in FPG at Week 4 | For FPG, blood was drawn after an overnight fast of at least 8 hours (except water). | Baseline and Week 4 | 
| Change From Baseline in FPG at Week 2 | For FPG, blood was drawn after an overnight fast of at least 8 hours (except water). | Baseline and Week 2 | 
| Number of Participants Who Experienced an Adverse Event (AE) | An adverse event is defined 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. The table below includes all data collected since first dose of study drug. | Up to 63 days (including run-in, treatment period, and follow-up) | 
| Number of Participants Who Discontinued Study Drug Due to an AE | An adverse event is defined 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. The table below includes all data collected since first dose of study drug. Discontinuation of study drug due to an AE includes temporary and permanent discontinuation of study drug due to an AE. | Up to 28 days (treatment period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes, hypertension, ambulatory blood pressure monitoring