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TerminatedNCT00806585Updated Sep 21, 2015Results posted

Dose-ranging Study to Evaluate the Effectiveness and Tolerability of MK0736 in Patients With Type 2 Diabetes Mellitus (T2DM) and Hypertension (0736-007)

A Phase 2 interventional study of MK-0736 and Comparator: Placebo in Type 2 Diabetes Mellitus and Hypertension, sponsored by Merck Sharp & Dohme LLC. Terminated. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2015-09-21.

Sponsored by Merck Sharp & Dohme LLC · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
620
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

The study will assess the efficacy and tolerability of MK0736 in patients with Type 2 Diabetes Mellitus and Hypertension who are on ongoing therapy with Angiotensin-Converting Enzyme or Angiotensin Receptor Blocker. After a 3 to 5 week pre-randomization phase, patients will be randomized to either MK0736 (3 doses), placebo, or hydrochlorothiazide (HCTZ). The study will also include a 3 week, posttreatment follow-up period.

02

Conditions studied

  • Type 2 Diabetes Mellitus
  • Hypertension
03

In context

Hypertension

6,689 studies on the registry are indexed under Hypertension; 965 are open to participants now.

This study's enrollment of 620 is above the median of 90 across 4,995 interventional studies indexed under Hypertension.

Browse Hypertension studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Must be 18 to 75 years of age
  • Type 2 Diabetes Mellitus (Glycohemoglobin [A1CHbA1c]: 7 to 10%)
  • Hypertension: Diastolic blood pressure (DBP; 85 to 99 mm Hg) and systolic blood pressure (SBP; 120 to 159 mm Hg)
  • LDL-C \< 140 mg/dL
  • On stable treatment with an Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB)

Exclusion criteria

Exclusion Criteria:

  • History of Type I Diabetes mellitus or ketoacidosis
  • Patients taking 3 or more blood pressure lowering medications
  • Have severe chronic heart failure
  • History of certain diseases or conditions such as cardiac arrhythmias, heart attack, stroke, unstable angina, or decompensated vascular disease
  • History of cancer within the last 5 years
  • Human immunodeficiency virus (HIV) Positive
  • Have received treatment with any investigational drugs within the past 30 days
  • History of alcohol or drug abuse within the past 3 years
  • Body Mass Index ( BMI) >= 41 kg/m2
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
620 participants (actual)

Study arms

  • Experimental
    MK-0736 0.5 mg

    One MK-0736 0.5 mg tablet, orally, once daily for 24 weeks (Phase A). Participant will then be switched to MK-0736 8.0 mg, once daily for an additional 52 weeks (Phase B).

    Drug: MK-0736

  • Experimental
    MK-0736 2.0 mg

    One MK-0736 2.0 mg tablet, orally, once daily for 24 weeks (Phase A). Participant will then be switched to MK-0736 8.0 mg, once daily for 52 weeks (Phase B).

    Drug: MK-0736

  • Experimental
    MK-0736 8.0 mg

    One MK-0736 8.0 mg tablet, orally, once daily for 24 weeks (Phase A). Participant will continue to receive MK-0736 8.0 mg, once daily for 52 weeks (Phase B).

    Drug: MK-0736

  • Active comparator
    HCTZ 12.5 mg → MK-0736 8.0 mg

    one 12.5 mg hydrochlorothiazide (HCTZ) tablet daily, orally, for 12 weeks. Participant then switched to MK-0736 8.0 mg for 12 weeks (Phase A). Participant will continue to receive MK-0736 8.0 mg, once daily for an additional 52 weeks (Phase B).

    Drug: MK-0736 · Drug: Comparator: HCTZ

  • Placebo comparator
    Placebo

    One placebo tablet daily, orally, for 24 weeks (Phase A). Participant will continue to receive placebo, once daily for 52 weeks (Phase B)

    Drug: Comparator: Placebo

Interventions

  • DrugMK-0736
  • DrugComparator: Placebo
  • DrugComparator: HCTZ
06

What researchers measure

Primary outcomes

  1. Change From Baseline in Sitting Diastolic Blood Pressure (SiDBP) at Week 12

    Participant remained in the sitting position for at least 5 minutes before any blood pressure readings were recorded. Systolic and diastolic blood pressures were determined by taking 6 replicate measurements obtained 1 to 2 minutes apart. First reading was discarded and the average of the last 5 measurement was recorded.

    Time frame: Baseline and Week 12

  2. Change From Baseline in Sitting Systolic Blood Pressure (SiSBP) at Week 12

    Participant remained in the sitting position for at least 5 minutes before any blood pressure readings were recorded. Systolic and diastolic blood pressures were determined by taking 6 replicate measurements obtained 1 to 2 minutes apart. First reading was discarded and the average the last 5 measurement was recorded.

    Time frame: Baseline and Week 12

Secondary outcomes

  1. Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

    LDL-C calculated by the method of Friedewald equation at baseline and after 12 weeks of study drug administration

    Time frame: Baseline and Week 12

  2. Change From Baseline in Body Weight at Week 24

    Fasting weight was assessed at baseline and after 24 weeks of study drug administration and was measured after voiding, with shoes and socks off, wearing clinic gown to reduce variability and maintain consistency. Same standardized digital scale was used throughout the study.

    Time frame: Baseline and Week 24

  3. Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24

    HbA1c reported as a % and was measured at baseline and after 24 weeks of study drug administration

    Time frame: Baseline and Week 24

07

Results

Posted Dec 11, 2013

Participant flow

Participant flow — Overall Study
MilestoneMK-0736 0.5 mgMK-0736 2.0 mgMK-0736 8.0 mgHCTZ 12.5 mg → MK-0736 8.0 mgPlacebo
Started13713414171137
Completed10510310956106
Not completed3231321531
Withdrew: Study terminated by sponsor00120
Withdrew: Protocol violation31200
Withdrew: Physician decision02301
Withdrew: Lost to follow-up21225
Withdrew: Lack of efficacy10000
Withdrew: Adverse event15342
Withdrew: Withdrawal by subject1089311
Withdrew: Completion status unknown151412412

Outcome measures

PrimaryChange From Baseline in Sitting Diastolic Blood Pressure (SiDBP) at Week 12

Participant remained in the sitting position for at least 5 minutes before any blood pressure readings were recorded. Systolic and diastolic blood pressures were determined by taking 6 replicate measurements obtained 1 to 2 minutes apart. First reading was discarded and the average of the last 5 measurement was recorded.

Time frame:
Baseline and Week 12
Reported as:
Least squares mean · mmHg
Change From Baseline in Sitting Diastolic Blood Pressure (SiDBP) at Week 12
mmHgMK-0736 0.5 mgMK-0736 2.0 mgMK-0736 8.0 mgHCTZ 12.5 mg → MK-0736 8.0 mgPlacebo
Change From Baseline in Sitting Diastolic Blood Pressure (SiDBP) at Week 12-5.8 ± 0.7-5.7 ± 0.7-6.7 ± 0.7-7.7 ± 1.0-5.6 ± 0.7
Statistical analysis
  • MK-0736 8.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.253 · Difference in least squares means: -1.1 · 95% CI -3.1 to 0.8Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 2.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.919 · Difference in least squares means: -0.1 · 95% CI -2.1 to 1.9Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 0.5 mg vs Placebo · Constrained longitudinal data analysis · p = 0.829 · Difference in least squares means: -0.2 · 95% CI -2.2 to 1.8Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • HCTZ 12.5 mg → MK-0736 8.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.074 · Difference in least squares means: -2.1 · 95% CI -4.5 to 0.2Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 8.0 mg vs HCTZ 12.5 mg → MK-0736 8.0 mg · Constrained longitudinal data analysis · p = 0.393 · Difference in least squares means: 1.0 · 95% CI -1.3 to 3.3Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 2.0 mg vs HCTZ 12.5 mg → MK-0736 8.0 mg · Constrained longitudinal data analysis · p = 0.088 · Difference in least squares means: 2.0 · 95% CI -0.3 to 4.4Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 0.5 mg vs HCTZ 12.5 mg → MK-0736 8.0 mg · Constrained longitudinal data analysis · p = 0.108 · Difference in least squares means: 1.9 · 95% CI -0.4 to 4.3Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
PrimaryChange From Baseline in Sitting Systolic Blood Pressure (SiSBP) at Week 12

Participant remained in the sitting position for at least 5 minutes before any blood pressure readings were recorded. Systolic and diastolic blood pressures were determined by taking 6 replicate measurements obtained 1 to 2 minutes apart. First reading was discarded and the average the last 5 measurement was recorded.

Time frame:
Baseline and Week 12
Reported as:
Least squares mean · mmHg
Change From Baseline in Sitting Systolic Blood Pressure (SiSBP) at Week 12
mmHgMK-0736 0.5 mgMK-0736 2.0 mgMK-0736 8.0 mgHCTZ 12.5 mg → MK-0736 8.0 mgPlacebo
Change From Baseline in Sitting Systolic Blood Pressure (SiSBP) at Week 12-5.7 ± 1.1-7.2 ± 1.1-6.3 ± 1.1-12.4 ± 1.5-5.4 ± 1.2
Statistical analysis
  • MK-0736 8.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.543 · Difference in least squares means: -0.9 · 95% CI -4.0 to 2.1Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 2.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.246 · Difference in least squares means: -1.8 · 95% CI -4.9 to 1.3Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 0.5 mg vs Placebo · Constrained longitudinal data analysis · p = 0.821 · Difference in least squares means: -0.4 · 95% CI -3.5 to 2.7Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • HCTZ 12.5 mg → MK-0736 8.0 mg vs Placebo · Constrained longitudinal data analysis · p = <0.001 · Difference in least squares means: -7.0 · 95% CI -10.7 to -3.3Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 8.0 mg vs HCTZ 12.5 mg → MK-0736 8.0 mg · Constrained longitudinal data analysis · p = 0.001 · Difference in least squares means: 6.1 · 95% CI 2.4 to 9.8Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 2.0 mg vs HCTZ 12.5 mg → MK-0736 8.0 mg · Constrained longitudinal data analysis · p = 0.006 · Difference in least squares means: 5.2 · 95% CI 1.5 to 8.9Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 0.5 mg vs HCTZ 12.5 mg → MK-0736 8.0 mg · Constrained longitudinal data analysis · p = <0.001 · Difference in least squares means: 6.7 · 95% CI 3.0 to 10.4Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
SecondaryPercent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

LDL-C calculated by the method of Friedewald equation at baseline and after 12 weeks of study drug administration

Time frame:
Baseline and Week 12
Reported as:
Least squares mean · Percentage Change
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Percentage ChangeMK-0736 0.5 mgMK-0736 2.0 mgMK-0736 8.0 mgHCTZ 12.5 mg → MK-0736 8.0 mgPlacebo
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 121.1 ± 2.33.9 ± 2.50.6 ± 2.52.8 ± 3.52.0 ± 2.5
Statistical analysis
  • MK-0736 8.0 mg vs Placebo · ANCOVA · p = 0.684 · Difference in least squares means: -1.4 · 95% CI -8.3 to 5.5Fixed effects for treatment baseline, stratification, time, interaction of time by stratification and treatments factors and a random subject effect
  • MK-0736 2.0 mg vs Placebo · ANCOVA · p = 0.597 · Difference in least squares means: 1.8 · 95% CI -5.0 to 8.7Fixed effects for treatment baseline, stratification, time, interaction of time by stratification and treatments factors and a random subject effect
  • MK-0736 0.5 mg vs Placebo · ANCOVA · p = 0.793 · Difference in least squares means: -0.9 · 95% CI -7.6 to 5.8Fixed effects for treatment baseline, stratification, time, interaction of time by stratification and treatments factors and a random subject effect
  • HCTZ 12.5 mg → MK-0736 8.0 mg vs Placebo · ANCOVA · p = 0.854 · Difference in least squares means: 0.8 · 95% CI -7.6 to 9.2Fixed effects for treatment baseline, stratification, time, interaction of time by stratification and treatments factors and a random subject effect
SecondaryChange From Baseline in Body Weight at Week 24

Fasting weight was assessed at baseline and after 24 weeks of study drug administration and was measured after voiding, with shoes and socks off, wearing clinic gown to reduce variability and maintain consistency. Same standardized digital scale was used throughout the study.

Time frame:
Baseline and Week 24
Reported as:
Least squares mean · kg
Change From Baseline in Body Weight at Week 24
kgMK-0736 0.5 mgMK-0736 2.0 mgMK-0736 8.0 mgHCTZ 12.5 mg → MK-0736 8.0 mgPlacebo
Change From Baseline in Body Weight at Week 24-0.7 ± 0.5-1.4 ± 0.5-1.3 ± 0.5-1.6 ± 0.70.6 ± 0.5
Statistical analysis
  • MK-0736 8.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.006 · Difference in least squares means: -1.9 · 95% CI -3.2 to -0.5Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 2.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.004 · Difference in least squares means: -2.0 · 95% CI -3.3 to -0.6Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 0.5 mg vs Placebo · Constrained longitudinal data analysis · p = 0.066 · Diffference in least squares means: -1.3 · 95% CI -2.6 to 0.1Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • HCTZ 12.5 mg → MK-0736 8.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.008 · Difference in least squares means: -2.2 · 95% CI -3.7 to -0.6Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
SecondaryChange From Baseline in Hemoglobin A1c (HbA1c) at Week 24

HbA1c reported as a % and was measured at baseline and after 24 weeks of study drug administration

Time frame:
Baseline and Week 24
Reported as:
Least squares mean · Percentage Change
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24
Percentage ChangeMK-0736 0.5 mgMK-0736 2.0 mgMK-0736 8.0 mgHCTZ 12.5 mg → MK-0736 8.0 mgPlacebo
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24-0.10 ± 0.09-0.16 ± 0.10-0.06 ± 0.09-0.20 ± 0.130.13 ± 0.10
Statistical analysis
  • MK-0736 8.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.152 · Difference in least squares means: -0.18 · 95% CI -0.44 to 0.07Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 2.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.035 · Difference in least sqaures means: -0.28 · 95% CI -0.54 to -0.02Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • MK-0736 0.5 mg vs Placebo · Constrained longitudinal data analysis · p = 0.095 · Difference in least squares means: -0.22 · 95% CI -0.48 to 0.04Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment
  • HCTZ 12.5 mg → MK-0736 8.0 mg vs Placebo · Constrained longitudinal data analysis · p = 0.045 · Difference in least squares means: -0.32 · 95% CI -0.63 to -0.01Model included terms for treatment, stratification factor, time, interaction of time by stratification factor and the interaction of time by treatment

Adverse events

Collected over 76 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
MK-0736 0.5 mg—9/137 (6.6%)46/137 (33.6%)
MK-0736 2.0 mg—7/134 (5.2%)54/134 (40.3%)
MK-0736 8.0 mg—6/141 (4.3%)54/141 (38.3%)
HCTZ 12.5 mg → MK-0736 8.0 mg—0/71 (0%)25/71 (35.2%)
Placebo—5/137 (3.6%)43/137 (31.4%)
Most frequent serious events
Showing 10 of 27
Most frequent serious events
EventMK-0736 0.5 mgMK-0736 2.0 mgMK-0736 8.0 mgHCTZ 12.5 mg → MK-0736 8.0 mgPlacebo
Angina unstableCardiac disorders0/1371/1340/1410/711/137
Cardiac failureCardiac disorders0/1371/1340/1410/710/137
Coronary artery diseaseCardiac disorders1/1371/1340/1410/710/137
Myocardial infarctionCardiac disorders1/1371/1340/1410/710/137
GastritisGastrointestinal disorders0/1371/1340/1410/710/137
Oedema peripheralGeneral disorders0/1371/1341/1410/710/137
Colon neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1371/1340/1410/710/137
Arteriosclerosis coronary arteryCardiac disorders1/1370/1340/1410/710/137
Chest discomfortGeneral disorders0/1370/1340/1410/711/137
Cholecystitis acuteHepatobiliary disorders0/1370/1340/1410/711/137
Most frequent other events
Most frequent other events
EventMK-0736 0.5 mgMK-0736 2.0 mgMK-0736 8.0 mgHCTZ 12.5 mg → MK-0736 8.0 mgPlacebo
HypoglycaemiaMetabolism and nutrition disorders24/13724/13428/1419/7127/137
Upper respiratory tract infectionInfections and infestations8/13710/1347/1414/717/137
Low density lipoprotein increasedInvestigations9/13710/1349/1415/714/137
HeadacheNervous system disorders4/1378/13410/1414/718/137
HypertensionVascular disorders4/1374/1349/1411/715/137
NasopharyngitisInfections and infestations2/1378/1343/1412/715/137
Oedema peripheralGeneral disorders1/1372/1348/1412/712/137

Baseline characteristics

Age, Continuous
Age, Continuous(years)MK-0736 0.5 mgMK-0736 2.0 mgMK-0736 8.0 mgHCTZ 12.5 mg → MK-0736 8.0 mgPlaceboTotal
Median58.0 (37 to 75)60.0 (36 to 74)58.0 (20 to 74)57.0 (37 to 74)58.0 (30 to 75)58.0 (20 to 75)
Sex: Female, Male
Sex: Female, Male(Participants)MK-0736 0.5 mgMK-0736 2.0 mgMK-0736 8.0 mgHCTZ 12.5 mg → MK-0736 8.0 mgPlaceboTotal
Female4855633450250
Male8979783787370
08

Study locations

No study locations are listed for this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 21, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00806585
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Dec 11, 2008
Start date
Dec 2008
Primary completion
Mar 2010
Completion
Jun 2010
Results posted
Dec 11, 2013
Last update
Sep 21, 2015

Study contacts

Medical Monitor
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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