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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)

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ClinicalTrials.gov Identifier: NCT01096667
Recruitment Status : Completed
First Posted : March 31, 2010
Results First Posted : December 13, 2017
Last Update Posted : December 13, 2017
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Hypertension 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 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 194 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : May 17, 2010
Primary Completion Date : February 9, 2011
Study Completion Date : February 25, 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: Placebo
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
Placebo to ertuglilflozin tablet 1 or 5 mg once daily for 28 days
Drug: Placebo to HCTZ
Placebo to HCTZ 12.5 mg capsule once daily for 28 days
Drug: Placebo to ertuglilflozin 25 mg
Placebo to ertuglilflozin tablet 25 mg once daily for 28 days
Experimental: Ertugliflozin 1 mg
Ertugliflozin 1 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days
Drug: Ertugliflozin 1 mg
Ertugliflozin tablet 1 mg once daily for 28 days
Drug: Placebo to HCTZ
Placebo to HCTZ 12.5 mg capsule once daily for 28 days
Drug: Placebo to ertuglilflozin 25 mg
Placebo to ertuglilflozin tablet 25 mg once daily for 28 days
Experimental: Ertugliflozin 5 mg
Ertugliflozin 5 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days
Drug: Ertugliflozin 5 mg
Ertugliflozin tablet 5 mg once daily for 28 days
Drug: Placebo to HCTZ
Placebo to HCTZ 12.5 mg capsule once daily for 28 days
Drug: Placebo to ertuglilflozin 25 mg
Placebo to ertuglilflozin tablet 25 mg once daily for 28 days
Experimental: Ertugliflozin 25 mg
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
Placebo to ertuglilflozin tablet 1 or 5 mg once daily for 28 days
Drug: Ertugliflozin 25 mg
Ertugliflozin tablet 25 mg once daily for 28 days
Drug: Placebo to HCTZ
Placebo to HCTZ 12.5 mg capsule once daily for 28 days
Active Comparator: HCTZ 12.5mg
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
Placebo to ertuglilflozin tablet 1 or 5 mg once daily for 28 days
Drug: HCTZ 12.5mg
Hydrocholorthiazide (HCTZ) 12.5 mg capsule once daily for 28 days
Drug: Placebo to ertuglilflozin 25 mg
Placebo to ertuglilflozin tablet 25 mg once daily for 28 days



Primary Outcome Measures :
  1. Baseline 24-hour Average Systolic Blood Pressure (SBP) [ Time Frame: 24 hours ]
    Baseline 24-hour average SBP was assessed using 24-hour ambulatory blood pressure monitoring (ABPM).

  2. Change From Baseline on 24-hour Average SBP at Week 4 [ Time Frame: Baseline and 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 :
  1. Baseline Average Daytime and Nighttime SBP [ Time Frame: Daytime: 16 hours; Nighttime: 8 hours ]
    Daytime was defined as 0600 to 2159 hours, inclusive, local time. Nighttime was defined as 2200 to 0559 hours, inclusive, local time.

  2. Change From Baseline on Daytime Average SBP at Week 4 [ Time Frame: Baseline and 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.

  3. Change From Baseline on Nighttime Average SBP at Week 4 [ Time Frame: Baseline and 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.

  4. Baseline Seated, Triplicate Trough SBP [ Time Frame: Baseline ]
    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.

  5. Change From Baseline in Seated, Triplicate Trough SBP at Week 4 [ Time Frame: Baseline and 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.

  6. Baseline 24-hour, Daytime and Nightime Average Diastolic Blood Pressure (DBP) [ Time Frame: up to 24 hours ]
    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.

  7. Change From Baseline on 24-hour Average DBP at Week 4 [ Time Frame: Baseline and Week 4 ]
    Change from baseline on 24-hour average DBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF.

  8. Change From Baseline on Daytime Average DBP at Week 4 [ Time Frame: Baseline and 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.

  9. Change From Baseline on Nighttime Average DBP at Week 4 [ Time Frame: Baseline and 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.

  10. Baseline Seated, Triplicate Trough DBP [ Time Frame: Baseline ]
    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.

  11. Change From Baseline in Seated, Triplicate Trough DBP at Week 4 [ Time Frame: Baseline and 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.

  12. Baseline 24-hour, Daytime and Nightime Average Heart Rate [ Time Frame: up to 24 hours ]
    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.

  13. Change From Baseline on 24-hour Average Heart Rate at Week 4 [ Time Frame: Baseline and Week 4 ]
    Change from baseline in 24-hour average heart rate at Week 4 using 24 hour ABPM.

  14. Change From Baseline on Daytime Average Heart Rate at Week 4 [ Time Frame: Baseline and 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.

  15. Change From Baseline on Nighttime Average Heart Rate at Week 4 [ Time Frame: Baseline and 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.

  16. Baseline Seated, Triplicate Trough Heart Rate [ Time Frame: Baseline ]
    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.

  17. Change From Baseline in Seated, Triplicate Trough Heart Rate at Week 4 [ Time Frame: Baseline and 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.

  18. Baseline 24-hour Average Urinary Glucose Excretion [ Time Frame: 24 hours ]
    Urinary glucose excetion was corrected for a duration of 24 hours (with appropriate duration of collection defined as >20 hours and <28 hours).

  19. Change From Baseline on 24-hour Urinary Glucose Excretion at Week 4 [ Time Frame: Baseline and 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.

  20. Baseline Fasting Plasma Glucose (FPG) [ Time Frame: Baseline ]
    For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).

  21. Change From Baseline in FPG at Week 4 [ Time Frame: Baseline and Week 4 ]
    For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).

  22. Change From Baseline in FPG at Week 2 [ Time Frame: Baseline and Week 2 ]
    For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).

  23. Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to 63 days (including run-in, treatment period, and follow-up) ]
    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.

  24. Number of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to 28 days (treatment period) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01096667


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Pfizer
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01096667     History of Changes
Other Study ID Numbers: 8835-042
B1521004 ( Other Identifier: Pfizer protocol number )
MK-8835-042 ( Other Identifier: Merck Protocol Number )
First Posted: March 31, 2010    Key Record Dates
Results First Posted: December 13, 2017
Last Update Posted: December 13, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
type 2 diabetes
hypertension
ambulatory blood pressure monitoring

Additional relevant MeSH terms:
Diabetes Mellitus
Hypertension
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Diseases
Cardiovascular Diseases
Hydrochlorothiazide
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action