NCT00868790

Brief Summary

This study assessed the safety and efficacy of MK-3577. The primary efficacy hypothesis was that, after 4 weeks of treatment, either the morning (AM) administration or the evening (PM) administration of MK-3577 provides superior reduction of 24-hour weighted mean glucose (WMG) levels compared to placebo (PLA). The primary safety hypothesis was that MK-3577 is well tolerated compared to placebo.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
118

participants targeted

Target at P50-P75 for phase_2 type-2-diabetes-mellitus

Timeline
Completed

Started Mar 2009

Typical duration for phase_2 type-2-diabetes-mellitus

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 24, 2009

Completed
Same day until next milestone

Study Start

First participant enrolled

March 24, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 25, 2009

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 12, 2010

Completed
1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 13, 2010

Completed
6.5 years until next milestone

Results Posted

Study results publicly available

January 11, 2017

Completed
Last Updated

September 10, 2018

Status Verified

August 1, 2018

Enrollment Period

1.3 years

First QC Date

March 24, 2009

Results QC Date

November 14, 2016

Last Update Submit

August 9, 2018

Conditions

Outcome Measures

Primary Outcomes (3)

  • Change From Baseline (BL) After 4-Week Treatment in Weighted Mean Glucose (WMG)

    The primary efficacy outcome in this study was the assessment of 24-hour weighted mean glucose (WMG) levels for domiciled participants after 4-week treatment (Periods 1 and 2 only). At selected study sites, a subset of participants domiciled (stayed) overnight and underwent 24-hour blood sampling at the Week 0 Visit (Baseline), Week 4 Visit (end of Period 1), and Week 8 Visit (end of Period 2). Domiciled participants were not expected to follow a weight-maintaining diet while receiving standard meals from a dietician or licensed healthcare professional. WMG was calculated as the weighted average value of the glucose from the 24-hour blood sample (for Baseline, Week 4, and Week 8) and analyzed using a Longitudinal Data Analysis (LDA) model. Results were expressed as the change from baseline after 4-week treatment in 24-hour WMG.

    Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit

  • Number of Participants With At Least One Adverse Event (AE) in the Treatment or Post-Treatment Periods

    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, is also an AE.

    From first dose of study treatment (Week 0 Visit) to Week 18 Post-study Visit (up to 18 weeks).

  • Number of Participants Who Discontinued Study Treatment Due to an AE

    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, is also an AE.

    From first dose of study treatment (Week 0 Visit) to Week 16 Visit (up to 16 weeks).

Secondary Outcomes (3)

  • Change From Baseline (BL) After 4-Week Treatment in Fasting Plasma Glucose (FPG)

    Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit, Week 12 Visit, Week 16 Visit

  • Change From BL After 4-Week Treatment in 2-hour Post-Meal Glucose (PMG) Levels

    Week 0 Visit (Baseline), Week 4 Visit, Week 8 visit

  • Percentage Change From Baseline (BL) After 4-Week Treatment in Low-Density Lipoprotein C (LDL-C) Levels

    Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit, Week 12 Visit, and Week 16 Visit

Study Arms (14)

PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1)

EXPERIMENTAL

Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.

Drug: MK-3577Drug: Placebo to MK-3577Drug: Placebo to Metformin

MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2)

EXPERIMENTAL

Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.

Drug: MK-3577Drug: Placebo to MK-3577Drug: Placebo to Metformin

MK-3577 QD PM→MK-3577 BID→PLA→MK-3577 QD AM (Arm 3)

EXPERIMENTAL

Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed MK- 3577 25 mg BID for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4.

Drug: MK-3577Drug: Placebo to MK-3577

MK-3577 BID→MK-3577 QD PM→MK-3577 QD AM→PLA (Arm 4)

EXPERIMENTAL

Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.

Drug: MK-3577Drug: Placebo to MK-3577

PLA→MK-3577 BID→MK-3577 QD AM→MK-3577 QD PM (Arm 5)

EXPERIMENTAL

Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4.

Drug: MK-3577Drug: Placebo to MK-3577

MK-3577 QD AM→MK-3577 QD PM→PLA→MK-3577 BID (Arm 6)

EXPERIMENTAL

Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4.

Drug: MK-3577Drug: Placebo to MK-3577

MK-3577 QD PM→MK-3577 QD AM→MK-3577 BID→PLA (Arm 7)

EXPERIMENTAL

Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.

Drug: MK-3577Drug: Placebo to MK-3577

MK-3577 BID→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 8)

EXPERIMENTAL

Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4.

Drug: MK-3577Drug: Placebo to MK-3577

PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9)

EXPERIMENTAL

Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.

Drug: MK-3577Drug: Placebo to MK-3577Drug: Placebo to Metformin

MK-3577 QD AM→MK-3577 BID→MK-3577 QD PM→PLA (Arm 10)

EXPERIMENTAL

Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.

Drug: MK-3577Drug: Placebo to MK-3577

MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11)

EXPERIMENTAL

Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.

Drug: MK-3577Drug: Placebo to MK-3577Drug: Placebo to Metformin

MK-3577 BID→MK-3577 QD AM→PLA→MK-3577 QD PM (Arm 12)

EXPERIMENTAL

Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4.

Drug: MK-3577Drug: Placebo to MK-3577

PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)

EXPERIMENTAL

Domiciled participants were to receive oral treatment with dose-matched placebo to metformin (METF) for 4 weeks during Period 1, followed by metformin 1000 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Participants in this arm were administered metformin placebo during Period 1 and active metformin during Period 2.

Drug: MK-3577Drug: Placebo to MK-3577Drug: MetforminDrug: Placebo to Metformin

METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)

EXPERIMENTAL

Domiciled participants were to receive oral treatment with metformin 1000 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to metformin for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. Participants in this arm were administered active metformin during Period 1 and metformin placebo during Period 2.

Drug: MK-3577Drug: Placebo to MK-3577Drug: MetforminDrug: Placebo to Metformin

Interventions

MK-3577 oral tablets totaling 6 mg in the evening (PM), 10 mg in the morning (AM), or 25 mg twice daily (BID) depending upon randomization, administered during a 4 week treatment period.

METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)MK-3577 BID→MK-3577 QD AM→PLA→MK-3577 QD PM (Arm 12)MK-3577 BID→MK-3577 QD PM→MK-3577 QD AM→PLA (Arm 4)MK-3577 BID→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 8)MK-3577 QD AM→MK-3577 BID→MK-3577 QD PM→PLA (Arm 10)MK-3577 QD AM→MK-3577 QD PM→PLA→MK-3577 BID (Arm 6)MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2)MK-3577 QD PM→MK-3577 BID→PLA→MK-3577 QD AM (Arm 3)MK-3577 QD PM→MK-3577 QD AM→MK-3577 BID→PLA (Arm 7)MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11)PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)PLA→MK-3577 BID→MK-3577 QD AM→MK-3577 QD PM (Arm 5)PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1)PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9)

Dose-matched placebo tablets to MK-3577 administered during a 4 week treatment period

METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)MK-3577 BID→MK-3577 QD AM→PLA→MK-3577 QD PM (Arm 12)MK-3577 BID→MK-3577 QD PM→MK-3577 QD AM→PLA (Arm 4)MK-3577 BID→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 8)MK-3577 QD AM→MK-3577 BID→MK-3577 QD PM→PLA (Arm 10)MK-3577 QD AM→MK-3577 QD PM→PLA→MK-3577 BID (Arm 6)MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2)MK-3577 QD PM→MK-3577 BID→PLA→MK-3577 QD AM (Arm 3)MK-3577 QD PM→MK-3577 QD AM→MK-3577 BID→PLA (Arm 7)MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11)PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)PLA→MK-3577 BID→MK-3577 QD AM→MK-3577 QD PM (Arm 5)PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1)PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9)

Two 500 mg tablets of metformin were administered twice daily (2000 mg total daily dose) to domiciled participants during a 4 week treatment period.

METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)

Two placebo tablets to metformin were administered twice daily (2000 mg total daily dose) to domiciled participants during a 4 week treatment period.

METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2)MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11)PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1)PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9)

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participant has type 2 diabetes
  • Participant is either not taking antihyperglycemic medications for the last 10 weeks OR is taking a single oral antihyperglycemic medication (but not a Peroxisome Proliferator-Activated Receptor gamma \[PPARg\] agonist) OR is taking a low-dose combination oral antihyperglycemic medication (not a PPARg agonist) at dose less than or equal to 50% of the maximum dose
  • Female participant is unable to have children

You may not qualify if:

  • Participant has a history of type 1 diabetes or ketoacidosis
  • Participant has been treated with a PPARg agonist in the last 12 weeks
  • Participant has been treated with insulin in the last 12 weeks
  • Participant has had prescription lipid-modifying drug therapy in the last 12 weeks
  • Participant has a history of coronary artery disease
  • Participant has had a stroke or transient ischemic attack
  • Participant has congestive heart failure

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Limitations and Caveats

A pre-specified interim analysis of the efficacy and safety data for the initial cohort of participants in this study (Cohort 1) determined that sufficient data had been accrued to assess the study hypotheses, thus the study was discontinued.

Results Point of Contact

Title
Vice President, Late Stage Development Group Leader
Organization
Merck Sharp & Dohme Corp

Study Officials

  • Medical Director

    Merck Sharp & Dohme LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 24, 2009

First Posted

March 25, 2009

Study Start

March 24, 2009

Primary Completion

July 12, 2010

Study Completion

July 13, 2010

Last Updated

September 10, 2018

Results First Posted

January 11, 2017

Record last verified: 2018-08

Data Sharing

IPD Sharing
Will share

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

More information

Available IPD Datasets

CSR Synopsis Link Access