Type 2 Diabetes MellitusPhase 3NCT01545388

Metformin Add-on Regimen Comparison Study in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431A-136)

A Phase 3 study testing Sitagliptin and Metformin in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 20 to 74 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: Sitagliptin and Metformin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 337 participants
Where: No sites listed yet
Study dates: 23 Feb 2012to 12 Mar 2013
Phase: Phase 3
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 20 to 74 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Type 2 Diabetes Mellitus (T2DM)
Currently being treated with diet/exercise and on stable dose of sitagliptin for ≥ 4 weeks, on any additional oral hypoglycemic agent (AHA) in the prior 8 weeks, and HbA1c ≥ 6.0% and ≤ 9.0%; or
Currently being treated with diet/exercise and on stable dose of sitagliptin for ≥ 10 weeks, not on any additional oral AHA in the prior 8 weeks, and HbA1c ≥ 6.5% and < 10.0%

Who cannot join

Type 1 diabetes mellitus,
Secondary diabetes mellitus, or
Gestational diabetes mellitus

About this study

Official title: A Phase III, Randomized, Placebo and Active-Controlled, Double-Blind Clinical Trial to Study the Efficacy and Safety of the Addition of Metformin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Diet/Exercise Therapy and Sitagliptin Monotherapy

This study will evaluate the effect of the addition of metformin once daily (q.d.) or twice daily (b.i.d.) to sitagliptin monotherapy in Japanese participants with Type 2 diabetes mellitus (T2DM) who have inadequate glycemic control with diet/exercise therapy and sitagliptin monotherapy. The primary hypotheses are that the addition of metformin 250 mg b.i.d. or metformin 500 mg q.d. is superior to the addition of placebo on the change from baseline in hemoglobin A1c (HbA1c) at 24 weeks and that the addition of metformin 500 mg q.d. is non-inferior to the addition of metformin 250 mg b.i.d. on the change from baseline in HbA1c at 24 weeks.

Conditions: Type 2 Diabetes Mellitus
Being tested: Sitagliptin, Metformin, Placebo
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.

SitagliptinDrug
Also called MK-0431/ONO-5435
Sitagliptin, orally, 50 or 100 mg tablet (continuation of the pre-study dose)
MetforminDrug
Metformin, orally, 500 mg daily (single dose; two 250 mg tablets) for 24 weeks
MetforminDrug
Metformin, orally, 500 mg daily (divided dose; 250 mg tablet b.i.d.) for 24 weeks
PlaceboDrug
Placebo to match metformin 250 mg tablets, orally, for 24 weeks

Study groups in NCT01545388
Study group	Role	What they receive
Metformin 500 mg q.d.	Experimental	Participants will receive sitagliptin daily (continuing their pre-study dose), 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening. Receives: Drug: Sitagliptin; Drug: Metformin; Drug: Placebo
Metformin 250 mg b.i.d.	Experimental	Participants will receive sitagliptin daily (continuing their pre-study dose), 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening. Receives: Drug: Sitagliptin; Drug: Metformin; Drug: Placebo
Placebo	Placebo comparator	Participants will receive sitagliptin daily (continuing their pre-study dose), 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening. Receives: Drug: Sitagliptin; Drug: Placebo

What is being measured

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

Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c)
Based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, other prior antihyperglycemic agent (AHA) therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups.
Measured: Baseline and Week 24
Percentage of Participants Who Experienced at Least One Adverse Event
Measured: Up to 26 weeks
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Measured: Up to 24 weeks

Secondary outcomes (1)

Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG)
Based on a cLDA model with terms for treatment, other prior AHA therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups.
Measured: Baseline and Week 24

Timeline

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

23 Feb 201212 Mar 2013

First posted6 Mar 2012 (estimated)
Study start23 Feb 2012
Primary completion12 Mar 2013
Study completion12 Mar 2013

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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 337 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01545388
Sponsor's protocol ID: 0431A-136
Other IDs: ONO-5435A
Status last verified: Jul 2018
First submitted: 1 Mar 2012
Last updated: 22 Aug 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
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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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Randomized, Placebo and Active-Controlled, Double-Blind Clinical Trial to Study the Efficacy and Safety of the Addition of Metformin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Diet/Exercise Therapy and Sitagliptin Monotherapy
ClinicalTrials.gov ID: NCT01545388
Acronym / sponsor ID: 0431A-136
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 337 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 23 Feb 2012 (actual)
Primary completion: 12 Mar 2013 (actual)
Study completion: 12 Mar 2013 (actual)
First posted: 6 Mar 2012 (estimated)
Results: Posted 26 Mar 2014

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Metformin 500 mg q.d.	Experimental	Drug: Sitagliptin, Drug: Metformin, Drug: PlaceboParticipants will receive sitagliptin daily (continuing their pre-study dose), 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
Metformin 250 mg b.i.d.	Experimental	Drug: Sitagliptin, Drug: Metformin, Drug: PlaceboParticipants will receive sitagliptin daily (continuing their pre-study dose), 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
Placebo	Placebo comparator	Drug: Sitagliptin, Drug: PlaceboParticipants will receive sitagliptin daily (continuing their pre-study dose), 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.

Who may qualify

Ages: 20 to 74 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Type 2 Diabetes Mellitus (T2DM)
Currently being treated with diet/exercise and on stable dose of sitagliptin for ≥ 4 weeks, on any additional oral hypoglycemic agent (AHA) in the prior 8 weeks, and HbA1c ≥ 6.0% and ≤ 9.0%; or
Currently being treated with diet/exercise and on stable dose of sitagliptin for ≥ 10 weeks, not on any additional oral AHA in the prior 8 weeks, and HbA1c ≥ 6.5% and < 10.0%

Key exclusion criteria (3 listed)

Type 1 diabetes mellitus,
Secondary diabetes mellitus, or
Gestational diabetes mellitus

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
SitagliptinAlso: MK-0431/ONO-5435Sitagliptin, orally, 50 or 100 mg tablet (continuation of the pre-study dose)	Drug	Metformin 250 mg b.i.d., Metformin 500 mg q.d., Placebo
MetforminMetformin, orally, 500 mg daily (single dose; two 250 mg tablets) for 24 weeks	Drug	Metformin 500 mg q.d.
MetforminMetformin, orally, 500 mg daily (divided dose; 250 mg tablet b.i.d.) for 24 weeks	Drug	Metformin 250 mg b.i.d.
PlaceboPlacebo to match metformin 250 mg tablets, orally, for 24 weeks	Drug	Metformin 250 mg b.i.d., Metformin 500 mg q.d., Placebo

Primary outcome

Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c)
Time frame: Baseline and Week 24
Based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, other prior antihyperglycemic agent (AHA) therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups.
Percentage of Participants Who Experienced at Least One Adverse Event
Time frame: Up to 26 weeks
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Time frame: Up to 24 weeks

1 secondary outcome

Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG)
Time frame: Baseline and Week 24

Results and safety

Results posted to the registry on 26 Mar 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Metformin 500 mg q.d.	138	130
Metformin 250 mg b.i.d.	133	122
Placebo	66	58

Primary outcome: Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c)

Time frame: Baseline and Week 24. Least squares mean (95% Confidence Interval). Unit: Percent of glycosylated hemoglobin

Measure	Metformin 500 mg q.d. n = 136	Metformin 250 mg b.i.d. n = 130	Placebo n = 66
Value	-0.434 (-0.553 to -0.315)	-0.587 (-0.708 to -0.467)	0.091 (-0.073 to 0.255)

Metformin 250 mg b.i.d. vs Placebo: Difference in least squares means: -0.678 (95% CI -0.868 to -0.489), p <0.001, cLDA
Metformin 500 mg q.d. vs Placebo: Difference in least squares means: -0.525 (95% CI -0.713 to -0.337), p <0.001, cLDA
Metformin 500 mg q.d. vs Metformin 250 mg b.i.d.: Difference in least squares means: 0.153 (95% CI 0.000 to 0.306)

Population analysed: Per-protocol population defined as all randomized participants who had at least one measurement (baseline or post-randomization), with participants and/or selected data excluded due to protocol violations.

Primary outcome: Percentage of Participants Who Experienced at Least One Adverse Event

Time frame: Up to 26 weeks. Number. Unit: Percentage of participants

Measure	Metformin 500 mg q.d. n = 138	Metformin 250 mg b.i.d. n = 133	Placebo n = 66
Value	65.9	67.7	60.6

Population analysed: All participants as treated defined as all randomized participants who received at least one dose of study treatment.

Primary outcome: Number of Participants Who Discontinued Study Drug Due to an Adverse Event

Time frame: Up to 24 weeks. Number. Unit: Participants

Measure	Metformin 500 mg q.d. n = 138	Metformin 250 mg b.i.d. n = 133	Placebo n = 66
Value	2	3	1

Population analysed: All participants as treated defined as all randomized participants who received at least one dose of study treatment.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to 26 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Metformin 500 mg q.d.	4 of 138 (2.9%)	29 of 138 (21%)	Not reported
Metformin 250 mg b.i.d.	2 of 133 (1.5%)	35 of 133 (26.3%)	Not reported
Placebo	0 of 66 (0%)	8 of 66 (12.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 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.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sitagliptin 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 3 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: finished, as of the sponsor's last update on 22 Aug 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 26 Mar 2014). 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 to Week 24 in Hemoglobin A1c (HbA1c) (time frame: Baseline and Week 24). 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 NCT01545388.

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 22 Aug 2018.