Type 2 Diabetes MellitusPhase 2NCT00868790

A Study of the Safety and Efficacy of MK-3577 in Participants With Type 2 Diabetes Mellitus (MK-3577-009)

A Phase 2 study testing MK-3577 and Metformin in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial 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). Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: MK-3577 and Metformin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 118 participants
Where: No sites listed yet
Study dates: 24 Mar 2009to 13 Jul 2010
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

About this study

Official title: A Phase IIa, Multicenter, Randomized, Placebo- and Active-Comparator Controlled, Cross-Over Clinical Trial to Study the Safety and Efficacy of MK-3577 in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

Read the detailed description

This was a 4-period/5-treatment crossover study. Each period was 4 weeks. The 5 treatments consisted of MK-3577 10 mg once daily (QD) in the AM, MK-3577 6 mg QD in the evening (PM), MK-3577 25 mg twice daily (BID), metformin 1000 mg BID, and placebo to MK-3577/placebo to metformin. Participants were to be randomized to one of 14 treatment sequence arms. A subset of participants in each group was to domicile (stay overnight) at selected clinical sites at Baseline, Week 4 (end of Period 1), and Week 8 (end of Period 2) to undergo 24-hr blood sample.

Conditions: Type 2 Diabetes Mellitus
Being tested: MK-3577, Placebo to MK-3577, Metformin, Placebo to Metformin
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-3577Drug
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.
Placebo to MK-3577Drug
Dose-matched placebo tablets to MK-3577 administered during a 4 week treatment period
MetforminDrug
Two 500 mg tablets of metformin were administered twice daily (2000 mg total daily dose) to domiciled participants during a 4 week treatment period.
Placebo to MetforminDrug
Two placebo tablets to metformin were administered twice daily (2000 mg total daily dose) to domiciled participants during a 4 week treatment period.

Study groups in NCT00868790
Study group	Role	What they receive
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. Receives: Drug: MK-3577; Drug: Placebo to MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: Placebo to MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: Placebo to MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: Placebo to MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: 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. Receives: Drug: MK-3577; Drug: Placebo to MK-3577; Drug: Metformin; Drug: 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. Receives: Drug: MK-3577; Drug: Placebo to MK-3577; Drug: Metformin; Drug: Placebo to Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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)
Fasting blood samples were obtained during study site visits at Baseline (Week 0 Visit) and Week 4 of each treatment period (Week 4 Visit, Week 8 Visit, Week 12 Visit, Week 16 Visit). Participants were counseled to fast (no food or drink except water and non-study medications, as directed) for at least 12 hours prior to all study visits. FPG was analyzed using an LDA model, and change from baseline (Week 0) after 4-week treatment in FPG was reported.
Measured: 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
Two-hour PMG was analyzed in both non-domiciled and domiciled participants. Non-domiciled participants completed a 3-point meal tolerance test (MTT) at Week 0 (Baseline) and Week 4 Visits of Treatment Period 1. Participants completed 12-hr fasting prior to the Week 0 (Baseline) and Week-4 clinic visits. Fasting blood samples were obtained at the beginning of these clinic visits, after which participants consumed a standardized meal (1 nutrition bar and 1 can of nutrition drink), and then completed the MTT, in which plasma glucose was measured at 30 min and 120 min (2 hr) post-meal. The 2-hr PMG data also include data from domiciled participants, based on 2-hr post-morning meal glucose levels in the 24-hr blood glucose sample at the Week 4 and Week 8 Visits. The 2-hour PMG was analyzed using an LDA model, and change from baseline (Week 0) after 4-week treatment in 2-hour PMG was reported.
Measured: 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
Blood samples were obtained from all participants to measure LDL-C levels at Week 0 (Baseline) and Week 4 of each treatment period (Week 4 Visit, Week 8 Visit, Week 12 Visit, and Week 16 Visit). For each visit, LDL-C was measured over 2 days. The average of duplicate measurements (when available) was used in the analysis.
Measured: Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit, Week 12 Visit, and Week 16 Visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Mar 200913 Jul 2010

First posted25 Mar 2009 (estimated)
Study start24 Mar 2009
Primary completion12 Jul 2010
Study completion13 Jul 2010

Why it stopped: Upon interim analysis, sufficient data was accrued to assess study hypotheses.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 118 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00868790
Sponsor's protocol ID: 3577-009
Other IDs: 2009_564, CTRI/2009/091/000614
Status last verified: Aug 2018
First submitted: 24 Mar 2009
Last updated: 10 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase IIa, Multicenter, Randomized, Placebo- and Active-Comparator Controlled, Cross-Over Clinical Trial to Study the Safety and Efficacy of MK-3577 in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control
ClinicalTrials.gov ID: NCT00868790
Acronym / sponsor ID: 3577-009
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Upon interim analysis, sufficient data was accrued to assess study hypotheses.
Enrolment: 118 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 24 Mar 2009 (actual)
Primary completion: 12 Jul 2010 (actual)
Study completion: 13 Jul 2010 (actual)
First posted: 25 Mar 2009 (estimated)
Results: Posted 11 Jan 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 14

Arm	Type	Receives
PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577, Drug: Placebo to MetforminParticipants 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.
MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577, Drug: Placebo to MetforminParticipants 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.
MK-3577 QD PM→MK-3577 BID→PLA→MK-3577 QD AM (Arm 3)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577Participants 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.
MK-3577 BID→MK-3577 QD PM→MK-3577 QD AM→PLA (Arm 4)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577Participants 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.
PLA→MK-3577 BID→MK-3577 QD AM→MK-3577 QD PM (Arm 5)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577Participants 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.
MK-3577 QD AM→MK-3577 QD PM→PLA→MK-3577 BID (Arm 6)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577Participants 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.
MK-3577 QD PM→MK-3577 QD AM→MK-3577 BID→PLA (Arm 7)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577Participants 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.
MK-3577 BID→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 8)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577Participants 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.
PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577, Drug: Placebo to MetforminParticipants 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.
MK-3577 QD AM→MK-3577 BID→MK-3577 QD PM→PLA (Arm 10)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577Participants 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.
MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577, Drug: Placebo to MetforminParticipants 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.
MK-3577 BID→MK-3577 QD AM→PLA→MK-3577 QD PM (Arm 12)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577Participants 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.
PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577, Drug: Metformin, Drug: Placebo to MetforminDomiciled 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.
METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)	Experimental	Drug: MK-3577, Drug: Placebo to MK-3577, Drug: Metformin, Drug: Placebo to MetforminDomiciled 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MK-3577MK-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.	Drug	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)
Placebo to MK-3577Dose-matched placebo tablets to MK-3577 administered during a 4 week treatment period	Drug	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)
MetforminTwo 500 mg tablets of metformin were administered twice daily (2000 mg total daily dose) to domiciled participants during a 4 week treatment period.	Drug	METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14), PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)
Placebo to MetforminTwo placebo tablets to metformin were administered twice daily (2000 mg total daily dose) to domiciled participants during a 4 week treatment period.	Drug	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)

Primary outcome

Change From Baseline (BL) After 4-Week Treatment in Weighted Mean Glucose (WMG)
Time frame: Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit
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.
Number of Participants With At Least One Adverse Event (AE) in the Treatment or Post-Treatment Periods
Time frame: From first dose of study treatment (Week 0 Visit) to Week 18 Post-study Visit (up to 18 weeks).
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.
Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: From first dose of study treatment (Week 0 Visit) to Week 16 Visit (up to 16 weeks).
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.

3 secondary outcomes

Change From Baseline (BL) After 4-Week Treatment in Fasting Plasma Glucose (FPG)
Time frame: 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
Time frame: 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
Time frame: Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit, Week 12 Visit, and Week 16 Visit

Results and safety

Results posted to the registry on 11 Jan 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1)	11	9
MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2)	8	7
MK-3577 QD PM→MK-3577 BID→PLA→MK-3577 QD AM (Arm 3)	4	4
MK-3577 BID→MK-3577 QD PM→MK-3577 QD AM→PLA (Arm 4)	4	4
PLA→MK-3577 BID→MK-3577 QD AM→MK-3577 QD PM (Arm 5)	19	18
MK-3577 QD AM→MK-3577 QD PM→PLA→MK-3577 BID (Arm 6)	3	2
MK-3577 QD PM→MK-3577 QD AM→MK-3577 BID→PLA (Arm 7)	4	4
MK-3577 BID→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 8)	20	17
PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9)	11	10
MK-3577 QD AM→MK-3577 BID→MK-3577 QD PM→PLA (Arm 10)	3	3
MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11)	9	9
MK-3577 BID→MK-3577 QD AM→PLA→MK-3577 QD PM (Arm 12)	4	4
PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)	7	7
METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)	11	9

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

Time frame: Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit. Least squares mean (Standard Error). Unit: mg/dL

Measure	Placebo (PLA) n = 38	MK-3577 AM n = 10	MK-3577 PM n = 11	MK-3577 BID n = 0	METF BID n = 15
Value	-1.6 (4.1)	-18.8 (6.8)	-25.0 (6.7)	–	-36.5 (6.1)

Placebo (PLA) vs MK-3577 AM: Least Squares Mean (LSM) Difference: -17.2 (90% CI -28.3 to -6.1), p = 0.013, LDA Model
Placebo (PLA) vs MK-3577 PM: LSM Difference: -23.4 (90% CI -34.5 to -12.4), p <0.001, LDA Model
Placebo (PLA) vs METF BID: LSM Difference: -34.9 (95% CI -44.8 to -25.0), p <0.001, LDA Model

Population analysed: All randomized domiciled participants receiving ≥1 dose of therapy and having 24-hour WMG measurement either at BL or end of Treatment Period 1 or 2. Number of Participants Analyzed=number of participants included in LDA model. Participants in MK-3577 25 mg BID group did not undergo 24-hour glucose sampling and were not analyzed.

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

Time frame: From first dose of study treatment (Week 0 Visit) to Week 18 Post-study Visit (up to 18 weeks).. Number. Unit: Participants

Measure	Placebo (PLA) n = 108	MK-3577 AM n = 106	MK-3577 PM n = 105	MK-3577 BID n = 89	METF BID n = 18
Value	28	30	22	28	6

Population analysed: All randomized participants who took ≥1 dose of study treatment (N=118). Because this was a cross-over study, participants were counted in more than one treatment group. AEs were reported by the treatment that participants were receiving at the time of the event. Not all participants received all treatments.

Primary outcome: Number of Participants Who Discontinued Study Treatment Due to an AE

Time frame: From first dose of study treatment (Week 0 Visit) to Week 16 Visit (up to 16 weeks).. Number. Unit: Participants

Measure	Placebo (PLA) n = 108	MK-3577 AM n = 106	MK-3577 PM n = 105	MK-3577 BID n = 89	METF BID n = 18
Value	2	2	2	3	1

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of study treatment (Week 0 Visit) to Week 18 Post-study Visit (up to 18 weeks).. Other adverse events reported at 5.0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 108 (0.9%)	3 of 108 (2.8%)	Not reported
MK-3577 AM	2 of 106 (1.9%)	4 of 106 (3.8%)	Not reported
MK-3577 PM	2 of 105 (1.9%)	3 of 105 (2.9%)	Not reported
MK-3577 BID	0 of 89 (0%)	5 of 89 (5.6%)	Not reported
METF BID	0 of 18 (0%)	6 of 18 (33.3%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MK-3577 and Metformin in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline (BL) After 4-Week Treatment in Weighted Mean Glucose (WMG) (time frame: Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00868790.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2018.