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

Primary Purpose

Diabetes Mellitus, Type 2, Hypertension

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Placebo to Ertuglilflozin 1 or 5 mg
Ertugliflozin 1 mg
Ertugliflozin 5 mg
Ertugliflozin 25 mg
HCTZ 12.5mg
Placebo to HCTZ
Placebo to ertuglilflozin 25 mg
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring type 2 diabetes, hypertension, ambulatory blood pressure monitoring

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Placebo Comparator

    Experimental

    Experimental

    Experimental

    Active Comparator

    Arm Label

    Placebo

    Ertugliflozin 1 mg

    Ertugliflozin 5 mg

    Ertugliflozin 25 mg

    HCTZ 12.5mg

    Arm Description

    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.

    Ertugliflozin 1 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days

    Ertugliflozin 5 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days

    Ertugliflozin 25 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to HCTZ once daily for 28 days

    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

    Outcomes

    Primary Outcome Measures

    Baseline 24-hour Average Systolic Blood Pressure (SBP)
    Baseline 24-hour average SBP was assessed using 24-hour ambulatory blood pressure monitoring (ABPM).
    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).

    Secondary Outcome Measures

    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.
    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.
    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 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.
    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 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.
    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.
    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.
    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 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.
    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 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.
    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.
    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.
    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 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.
    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 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).
    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 Fasting Plasma Glucose (FPG)
    For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).
    Change From Baseline in FPG at Week 4
    For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).
    Change From Baseline in FPG at Week 2
    For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).
    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.
    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.

    Full Information

    First Posted
    March 26, 2010
    Last Updated
    August 15, 2018
    Sponsor
    Merck Sharp & Dohme LLC
    Collaborators
    Pfizer
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01096667
    Brief Title
    Study of Safety and Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes And Hypertension (MK-8835-042)
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    May 17, 2010 (Actual)
    Primary Completion Date
    February 9, 2011 (Actual)
    Study Completion Date
    February 25, 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC
    Collaborators
    Pfizer

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Diabetes Mellitus, Type 2, Hypertension
    Keywords
    type 2 diabetes, hypertension, ambulatory blood pressure monitoring

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    194 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    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.
    Arm Title
    Ertugliflozin 1 mg
    Arm Type
    Experimental
    Arm Description
    Ertugliflozin 1 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days
    Arm Title
    Ertugliflozin 5 mg
    Arm Type
    Experimental
    Arm Description
    Ertugliflozin 5 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days
    Arm Title
    Ertugliflozin 25 mg
    Arm Type
    Experimental
    Arm Description
    Ertugliflozin 25 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to HCTZ once daily for 28 days
    Arm Title
    HCTZ 12.5mg
    Arm Type
    Active Comparator
    Arm Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to Ertuglilflozin 1 or 5 mg
    Intervention Description
    Placebo to ertuglilflozin tablet 1 or 5 mg once daily for 28 days
    Intervention Type
    Drug
    Intervention Name(s)
    Ertugliflozin 1 mg
    Intervention Description
    Ertugliflozin tablet 1 mg once daily for 28 days
    Intervention Type
    Drug
    Intervention Name(s)
    Ertugliflozin 5 mg
    Intervention Description
    Ertugliflozin tablet 5 mg once daily for 28 days
    Intervention Type
    Drug
    Intervention Name(s)
    Ertugliflozin 25 mg
    Intervention Description
    Ertugliflozin tablet 25 mg once daily for 28 days
    Intervention Type
    Drug
    Intervention Name(s)
    HCTZ 12.5mg
    Intervention Description
    Hydrocholorthiazide (HCTZ) 12.5 mg capsule once daily for 28 days
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to HCTZ
    Intervention Description
    Placebo to HCTZ 12.5 mg capsule once daily for 28 days
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to ertuglilflozin 25 mg
    Intervention Description
    Placebo to ertuglilflozin tablet 25 mg once daily for 28 days
    Primary Outcome Measure Information:
    Title
    Baseline 24-hour Average Systolic Blood Pressure (SBP)
    Description
    Baseline 24-hour average SBP was assessed using 24-hour ambulatory blood pressure monitoring (ABPM).
    Time Frame
    24 hours
    Title
    Change From Baseline on 24-hour Average SBP at Week 4
    Description
    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).
    Time Frame
    Baseline and Week 4
    Secondary Outcome Measure Information:
    Title
    Baseline Average Daytime and Nighttime SBP
    Description
    Daytime was defined as 0600 to 2159 hours, inclusive, local time. Nighttime was defined as 2200 to 0559 hours, inclusive, local time.
    Time Frame
    Daytime: 16 hours; Nighttime: 8 hours
    Title
    Change From Baseline on Daytime Average SBP at Week 4
    Description
    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.
    Time Frame
    Baseline and Week 4
    Title
    Change From Baseline on Nighttime Average SBP at Week 4
    Description
    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.
    Time Frame
    Baseline and Week 4
    Title
    Baseline Seated, Triplicate Trough SBP
    Description
    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.
    Time Frame
    Baseline
    Title
    Change From Baseline in Seated, Triplicate Trough SBP at Week 4
    Description
    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.
    Time Frame
    Baseline and Week 4
    Title
    Baseline 24-hour, Daytime and Nightime Average Diastolic Blood Pressure (DBP)
    Description
    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.
    Time Frame
    up to 24 hours
    Title
    Change From Baseline on 24-hour Average DBP at Week 4
    Description
    Change from baseline on 24-hour average DBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF.
    Time Frame
    Baseline and Week 4
    Title
    Change From Baseline on Daytime Average DBP at Week 4
    Description
    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.
    Time Frame
    Baseline and Week 4
    Title
    Change From Baseline on Nighttime Average DBP at Week 4
    Description
    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.
    Time Frame
    Baseline and Week 4
    Title
    Baseline Seated, Triplicate Trough DBP
    Description
    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.
    Time Frame
    Baseline
    Title
    Change From Baseline in Seated, Triplicate Trough DBP at Week 4
    Description
    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.
    Time Frame
    Baseline and Week 4
    Title
    Baseline 24-hour, Daytime and Nightime Average Heart Rate
    Description
    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.
    Time Frame
    up to 24 hours
    Title
    Change From Baseline on 24-hour Average Heart Rate at Week 4
    Description
    Change from baseline in 24-hour average heart rate at Week 4 using 24 hour ABPM.
    Time Frame
    Baseline and Week 4
    Title
    Change From Baseline on Daytime Average Heart Rate at Week 4
    Description
    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.
    Time Frame
    Baseline and Week 4
    Title
    Change From Baseline on Nighttime Average Heart Rate at Week 4
    Description
    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.
    Time Frame
    Baseline and Week 4
    Title
    Baseline Seated, Triplicate Trough Heart Rate
    Description
    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.
    Time Frame
    Baseline
    Title
    Change From Baseline in Seated, Triplicate Trough Heart Rate at Week 4
    Description
    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.
    Time Frame
    Baseline and Week 4
    Title
    Baseline 24-hour Average Urinary Glucose Excretion
    Description
    Urinary glucose excetion was corrected for a duration of 24 hours (with appropriate duration of collection defined as >20 hours and <28 hours).
    Time Frame
    24 hours
    Title
    Change From Baseline on 24-hour Urinary Glucose Excretion at Week 4
    Description
    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.
    Time Frame
    Baseline and Week 4
    Title
    Baseline Fasting Plasma Glucose (FPG)
    Description
    For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).
    Time Frame
    Baseline
    Title
    Change From Baseline in FPG at Week 4
    Description
    For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).
    Time Frame
    Baseline and Week 4
    Title
    Change From Baseline in FPG at Week 2
    Description
    For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).
    Time Frame
    Baseline and Week 2
    Title
    Number of Participants Who Experienced an Adverse Event (AE)
    Description
    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.
    Time Frame
    Up to 63 days (including run-in, treatment period, and follow-up)
    Title
    Number of Participants Who Discontinued Study Drug Due to an AE
    Description
    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.
    Time Frame
    Up to 28 days (treatment period)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    25951755
    Citation
    Amin NB, Wang X, Mitchell JR, Lee DS, Nucci G, Rusnak JM. Blood pressure-lowering effect of the sodium glucose co-transporter-2 inhibitor ertugliflozin, assessed via ambulatory blood pressure monitoring in patients with type 2 diabetes and hypertension. Diabetes Obes Metab. 2015 Aug;17(8):805-8. doi: 10.1111/dom.12486. Epub 2015 Jun 17.
    Results Reference
    result
    PubMed Identifier
    34213819
    Citation
    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.
    Results Reference
    derived

    Learn more about this trial

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

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