Type 2 Diabetes MellitusPhase 3NCT01590797

A Study in China Evaluating the Safety and Efficacy of Adding Sitagliptin to Stable Therapy With Insulin With or Without Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-254)

A Phase 3 study testing Sitagliptin, Insulin 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 18 to 79 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: Sitagliptin, Insulin and Metformin
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 467 participants
Where: No sites listed yet
Study dates: 10 Jul 2012to 25 Jun 2014
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 18 to 79 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

has T2DM
is currently on a stable regimen of pre-mixed, intermediate-acting, or long-acting insulin at a dose of at least 12 U/day, either alone or in combination with metformin >=1500 mg/day for ≥ 10 weeks
has a Visit 1/Screening HbA1C between 7.5% and 11.0%
is a male, or a female who is highly unlikely to conceive during the study and for 14 days after the last dose of study medication

Who cannot join

has been treated with any antihyperglycemic therapies other than a protocol-required insulin (alone or with metformin) within the prior 12 weeks or has ever
been treated with a dipeptidyl peptidase-4 inhibitor or a glucagon-like peptide-1 mimetic or analogue
is currently on treatment with daily use (one or more injections per day) of
pre-prandial short-acting or rapid-acting insulin
has a history of 2 or more episodes of hypoglycemia resulting in seizure,
coma, or loss of consciousness, or has had recurrent episodes of hypoglycemia over the past 8 weeks

Show all 21Show fewer

has a history of intolerance or hypersensitivity, or has any contraindication to sitagliptin, insulin, or metformin
is on a weight loss program and not in the maintenance phase, or has started a weight loss medication or has undergone bariatric surgery within 12 months
has undergone a surgical procedure within 4 weeks or has planned major surgery during the study
has a medical history of active liver disease
has had new or worsening signs or symptoms of coronary heart disease within the past 3 months, or has acute coronary syndrome, coronary artery intervention, or stroke or transient ischemic neurological disorder
has a diagnosis of congestive heart failure with New York Heart Association Class III - IV cardiac status
has a systolic blood pressure ≥ 160 mmHg or a diastolic blood pressure ≥ 90 mmHg
has human immunodeficiency virus (HIV)
has severe peripheral vascular disease
is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks
has a history of malignancy ≤ 5 years before the study, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
has a clinically important hematological disorder (such as aplastic anemia,
myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
is pregnant or breast feeding, or is expecting to conceive or donate eggs during the study, including 14 days after the last dose of study medication
is a user of recreational or illicit drugs or has had a recent history of drug abuse

About this study

Official title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial in China to Study the Safety and Efficacy of the Addition of Sitagliptin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Insulin Therapy, Alone or in Combination With Metformin

A study to compare safety and efficacy of sitagliptin and placebo therapy when added to stable insulin alone or in combination with metformin in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis of this study is that after 24 weeks, the addition of sitagliptin compared with placebo provides greater reduction in hemoglobin A1C (HbA1C) in T2DM participants on insulin alone or in combination with metformin.

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

SitagliptinDrug
Also called Januvia®, MK-0431
Sitagliptin 100 mg once daily for 24 weeks
PlaceboDrug
Matching placebo once daily for 24 weeks
InsulinBiological
Participants can be on on pre-mixed (mixture of rapid- and long-acting insulin) or intermediate- or long-acting insulin at a dose of at least 12 U/day.
MetforminDrug
At randomization, participants will be stratified according to their use of metformin (on or not on). All participants receiving metformin will be required to be on a daily dose of metformin at least 1500 mg per day.

Study groups in NCT01590797
Study group	Role	What they receive
Sitagliptin	Experimental	Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period. Receives: Drug: Sitagliptin; Biological: Insulin; Drug: Metformin
Placebo	Placebo comparator	Participants treated with placebo matching sitagliptin, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period. Receives: Drug: Placebo; Biological: Insulin; Drug: Metformin

What is being measured

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

Change From Baseline in Hemoglobin A1C (HbA1C) Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin
Measured: Baseline and Week 24
Number of Participants With One or More Adverse Events
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Measured: Up to Week 26
Number of Participants Discontinuing Study Medication Due to an AE
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Measured: Up to Week 24

Secondary outcomes (2)

Change From Baseline in HbA1C Levels at Week 24 in Participants Receiving Insulin in Combination With Metformin
Measured: Baseline and Week 24
Change From Baseline in 2-Hour Post Meal Glucose Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin
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.

10 Jul 201225 Jun 2014

First posted3 May 2012 (estimated)
Study start10 Jul 2012
Primary completion11 Jun 2014
Study completion25 Jun 2014

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.
Publications (1)Papers the sponsor has linked to this study.
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: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 467 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01590797
Sponsor's protocol ID: 0431-254
Status last verified: Jul 2018
First submitted: 1 May 2012
Last updated: 17 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

Publications

Shankar RR, Bao Y, Han P, Hu J, Ma J, Peng Y, Wu F, Xu L, Engel SS, Jia W. Sitagliptin added to stable insulin therapy with or without metformin in Chinese patients with type 2 diabetes. J Diabetes Investig. 2017 May;8(3):321-329. doi: 10.1111/jdi.12585. Epub 2016 Dec 9.
PubMed 27740719

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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Study at a glance

From the registry record, last updated by the sponsor on 17 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial in China to Study the Safety and Efficacy of the Addition of Sitagliptin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Insulin Therapy, Alone or in Combination With Metformin
ClinicalTrials.gov ID: NCT01590797
Acronym / sponsor ID: 0431-254
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 467 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 10 Jul 2012 (actual)
Primary completion: 11 Jun 2014 (actual)
Study completion: 25 Jun 2014 (actual)
First posted: 3 May 2012 (estimated)
Results: Posted 27 Jan 2015

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: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Sitagliptin	Experimental	Drug: Sitagliptin, Biological: Insulin, Drug: MetforminParticipants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Placebo	Placebo comparator	Drug: Placebo, Biological: Insulin, Drug: MetforminParticipants treated with placebo matching sitagliptin, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.

Who may qualify

Ages: 18 to 79 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

has T2DM
is currently on a stable regimen of pre-mixed, intermediate-acting, or long-acting insulin at a dose of at least 12 U/day, either alone or in combination with metformin >=1500 mg/day for ≥ 10 weeks
has a Visit 1/Screening HbA1C between 7.5% and 11.0%
is a male, or a female who is highly unlikely to conceive during the study and for 14 days after the last dose of study medication

Key exclusion criteria (21 listed)

has been treated with any antihyperglycemic therapies other than a protocol-required insulin (alone or with metformin) within the prior 12 weeks or has ever
been treated with a dipeptidyl peptidase-4 inhibitor or a glucagon-like peptide-1 mimetic or analogue
is currently on treatment with daily use (one or more injections per day) of
pre-prandial short-acting or rapid-acting insulin
has a history of 2 or more episodes of hypoglycemia resulting in seizure,

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: Januvia®, MK-0431Sitagliptin 100 mg once daily for 24 weeks	Drug	Sitagliptin
PlaceboMatching placebo once daily for 24 weeks	Drug	Placebo
InsulinParticipants can be on on pre-mixed (mixture of rapid- and long-acting insulin) or intermediate- or long-acting insulin at a dose of at least 12 U/day.	Biological	Placebo, Sitagliptin
MetforminAt randomization, participants will be stratified according to their use of metformin (on or not on). All participants receiving metformin will be required to be on a daily dose of metformin at least 1500 mg per day.	Drug	Placebo, Sitagliptin

Primary outcome

Change From Baseline in Hemoglobin A1C (HbA1C) Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin
Time frame: Baseline and Week 24
Number of Participants With One or More Adverse Events
Time frame: Up to Week 26
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Number of Participants Discontinuing Study Medication Due to an AE
Time frame: Up to Week 24
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

2 secondary outcomes

Change From Baseline in HbA1C Levels at Week 24 in Participants Receiving Insulin in Combination With Metformin
Time frame: Baseline and Week 24
Change From Baseline in 2-Hour Post Meal Glucose Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin
Time frame: Baseline and Week 24

Results and safety

Results posted to the registry on 27 Jan 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sitagliptin	234	217
Placebo	233	217

Primary outcome: Change From Baseline in Hemoglobin A1C (HbA1C) Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin

Time frame: Baseline and Week 24. Least squares mean (95% Confidence Interval). Unit: A1C %

Measure	Sitagliptin n = 223	Placebo n = 219
Value	-0.67 (-0.79 to -0.55)	-0.32 (-0.44 to -0.20)

Sitagliptin vs Placebo: Mean Difference (Final Values): -0.34 (95% CI -0.50 to -0.19), p <0.001, Robust Regression

Population analysed: The Full Analysis Set (FAS) consisted of all randomized participants receiving insulin alone or in combination with metformin, took at least one dose of study treatment, had at least one observation for the analysis endpoint subsequent to the first dose of study treatment, and had baseline data for the analysis endpoint.

Primary outcome: Number of Participants With One or More Adverse Events

Time frame: Up to Week 26. Number. Unit: Participants

Measure	Sitagliptin n = 234	Placebo n = 233
Value	126	116

Population analysed: The All Patients as Treated (APaT) population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.

Primary outcome: Number of Participants Discontinuing Study Medication Due to an AE

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

Measure	Sitagliptin n = 234	Placebo n = 233
Value	4	2

Population analysed: The APaT population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.

2 secondary outcomes are reported in the full results.

Adverse events

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

Group	Serious adverse events	Other adverse events	Deaths
Sitagliptin	4 of 234 (1.7%)	83 of 234 (35.5%)	Not reported
Placebo	9 of 233 (3.9%)	68 of 233 (29.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27740719Shankar RR, Bao Y, Han P, Hu J, Ma J, Peng Y, Wu F, Xu L, Engel SS, Jia W. Sitagliptin added to stable insulin therapy with or without metformin in Chinese patients with type 2 diabetes. J Diabetes Investig. 2017 May;8(3):321-329. doi: 10.1111/jdi.12585. Epub 2016 Dec 9.
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 3 study testing Sitagliptin, Insulin 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 4 inclusion and 21 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 17 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 27 Jan 2015). 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 in Hemoglobin A1C (HbA1C) Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin (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 NCT01590797, which also lists 1 linked publication.

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 17 Aug 2018.