Type 2 Diabetes MellitusPhase 3NCT00350779

Sitagliptin Metformin/PPARg Agonist Combination Therapy Add-on (0431-052)

A Phase 3 study testing sitagliptin, rosiglitazone 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

A clinical study to determine the safety and efficacy of sitagliptin in patients with Type 2 Diabetes Mellitus who have inadequate glycemic control on metformin/peroxisome proliferator-activated receptor gamma (PPARg) agonist combination therapy. Read more about this study

Who is it for?: Ages 18 to 78 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: sitagliptin, rosiglitazone and metformin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 262 participants
Where: No sites listed yet
Study dates: 12 Jun 2006to 11 Jun 2008
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 78 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient has type 2 diabetes mellitus
Patient is inadequately controlled while taking two oral antidiabetic medications

Who cannot join

Patient has a history of type 1 diabetes mellitus or history of ketoacidosis
Patient required insulin therapy within the prior 3 months
Patient has been taking Byetta (R) (exenatide) within the prior 3 months

About this study

Official title: A Phase III Randomized, Placebo-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Sitagliptin (MK0431) in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Combination Therapy With Metformin and a PPARg Agonist

Conditions: Type 2 Diabetes Mellitus
Being tested: sitagliptin, Comparator: Placebo, rosiglitazone, metformin, glipizide
Keywords: Type 2 Diabetes Mellitus
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
Sitagliptin 100mg tablet each day for 54 weeks. All subjects will be given placebo to sitagliptin for a 2 week period.
Comparator: PlaceboDrug
Placebo to sitagliptin 100mg tablet each day for 54 weeks.
rosiglitazoneDrug
Also called Avandia
Subjects taking 4mg or greater rosiglitazone at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 4mg/day or no rosiglitazone at screening will be titrated to a stable dose of at least 4mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.
metforminDrug
Subjects taking 1500mg or greater metformin at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 1500mg/day or no metformin at screening will be titrated to a stable dose of at least 1500mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.
glipizideDrug
Also called Glucotrol
Subjects not meeting specific glycemic controls during the 54-week treatment period will use glipizide as rescue therapy. Glipizide will be titrated in 5mg doses up to a maximum 40mg each day. (In Canada, the rescue therapy will be a sulfonylurea agent marketed in that country.)

Study groups in NCT00350779
Study group	Role	What they receive
1	Experimental	Sitagliptin Receives: Drug: sitagliptin; Drug: rosiglitazone; Drug: metformin; Drug: glipizide
2	Placebo comparator	Placebo Receives: Drug: Comparator: Placebo; Drug: rosiglitazone; Drug: metformin; Drug: glipizide

What is being measured

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

Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.
Measured: Baseline and 18 Weeks

Secondary outcomes (5)

Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18
Change from baseline at Week 18 is defined as Week 18 minus Week 0
Measured: Baseline and 18 Weeks
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18
Change from baseline at Week 18 is defined as Week 18 minus Week 0
Measured: Baseline and Week 18
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.
Measured: Baseline and Week 54
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54
Change from baseline at Week 54 is defined as Week 54 minus Week 0
Measured: Baseline and Week 54
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54
Change from baseline at Week 54 is defined as Week 54 minus Week 0.
Measured: Baseline and Week 54

Timeline

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

12 Jun 200611 Jun 2008

First posted11 Jul 2006 (estimated)
Study start12 Jun 2006
Primary completion25 Sep 2007
Study completion11 Jun 2008

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: Double blind
Who is masked: Participant, Investigator
Enrolment: 262 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00350779
Sponsor's protocol ID: 0431-052
Other IDs: MK0431-052, 2006_507
Status last verified: Apr 2017
First submitted: 7 Jul 2006
Last updated: 12 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php

Publications

Dobs AS, Goldstein BJ, Aschner P, Horton ES, Umpierrez GE, Duran L, Hill JS, Chen Y, Golm GT, Langdon RB, Williams-Herman DE, Kaufman KD, Amatruda JM, Ferreira JC. Efficacy and safety of sitagliptin added to ongoing metformin and rosiglitazone combination therapy in a randomized placebo-controlled 54-week trial in patients with type 2 diabetes. J Diabetes. 2013 Mar;5(1):68-79. doi: 10.1111/j.1753-0407.2012.00223.x.
PubMed 22742523

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 12 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III Randomized, Placebo-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Sitagliptin (MK0431) in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Combination Therapy With Metformin and a PPARg Agonist
ClinicalTrials.gov ID: NCT00350779
Acronym / sponsor ID: 0431-052
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 Diabetes Mellitus
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 262 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 12 Jun 2006 (actual)
Primary completion: 25 Sep 2007 (actual)
Study completion: 11 Jun 2008 (actual)
First posted: 11 Jul 2006 (estimated)
Results: Posted 3 Jul 2009

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: 2

Arm	Type	Receives
1	Experimental	Drug: sitagliptin, Drug: rosiglitazone, Drug: metformin, Drug: glipizideSitagliptin
2	Placebo comparator	Drug: Comparator: Placebo, Drug: rosiglitazone, Drug: metformin, Drug: glipizidePlacebo

Who may qualify

Ages: 18 to 78 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Patient has type 2 diabetes mellitus
Patient is inadequately controlled while taking two oral antidiabetic medications

Key exclusion criteria (3 listed)

Patient has a history of type 1 diabetes mellitus or history of ketoacidosis
Patient required insulin therapy within the prior 3 months
Patient has been taking Byetta (R) (exenatide) within the prior 3 months

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: JanuviaSitagliptin 100mg tablet each day for 54 weeks. All subjects will be given placebo to sitagliptin for a 2 week period.	Drug	1
Comparator: PlaceboPlacebo to sitagliptin 100mg tablet each day for 54 weeks.	Drug	2
rosiglitazoneAlso: AvandiaSubjects taking 4mg or greater rosiglitazone at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 4mg/day or no rosiglitazone at screening will be titrated to a stable dose of at least 4mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.	Drug	1, 2
metforminSubjects taking 1500mg or greater metformin at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 1500mg/day or no metformin at screening will be titrated to a stable dose of at least 1500mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.	Drug	1, 2
glipizideAlso: GlucotrolSubjects not meeting specific glycemic controls during the 54-week treatment period will use glipizide as rescue therapy. Glipizide will be titrated in 5mg doses up to a maximum 40mg each day. (In Canada, the rescue therapy will be a sulfonylurea agent marketed in that country.)	Drug	1, 2

Primary outcome

Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18
Time frame: Baseline and 18 Weeks
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.

5 secondary outcomes

Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18
Time frame: Baseline and 18 Weeks
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18
Time frame: Baseline and Week 18
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54
Time frame: Baseline and Week 54
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54
Time frame: Baseline and Week 54
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54
Time frame: Baseline and Week 54

Results and safety

Results posted to the registry on 3 Jul 2009, 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 100 mg	170	148
Placebo	92	71

Primary outcome: Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18

Time frame: Baseline and 18 Weeks. Least squares mean (95% Confidence Interval). Unit: Percent

Measure	Sitagliptin 100 mg n = 168	Placebo n = 88
Value	-1.03 (-1.17 to -0.90)	-0.31 (-0.50 to -0.13)

Sitagliptin 100 mg vs Placebo: Mean Difference (Net): -0.72 (95% CI -0.95 to -0.49), p <0.001, ANCOVA

Population analysed: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 18, the last non-baseline observed measurement was carried forward to Week 18.

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sitagliptin 100 mg Data Through Week 18	2 of ?	20 of ?	Not reported
Placebo Data Through Week 18	2 of ?	14 of ?	Not reported
Sitagliptin 100 mg Data Through Week 54	14 of ?	70 of ?	Not reported
Placebo Data Through Week 54	4 of ?	35 of ?	Not reported

Limitations and caveats (from the sponsor): Non-serious adverse event results represent those events included in the primary safety analysis for this study (events occurred prior to initiation of glycemic rescue therapy). Site 0520039 was non-compliant with GDP, data was removed from analyses.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22742523Dobs AS, Goldstein BJ, Aschner P, Horton ES, Umpierrez GE, Duran L, Hill JS, Chen Y, Golm GT, Langdon RB, Williams-Herman DE, Kaufman KD, Amatruda JM, Ferreira JC. Efficacy and safety of sitagliptin added to ongoing metformin and rosiglitazone combination therapy in a randomized placebo-controlled 54-week trial in patients with type 2 diabetes. J Diabetes. 2013 Mar;5(1):68-79. doi: 10.1111/j.1753-0407.2012.00223.x.
Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

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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 Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing sitagliptin, rosiglitazone 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 2 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 12 May 2017. 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 3 Jul 2009). 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 HbA1c (Hemoglobin A1C) at Week 18 (time frame: Baseline and 18 Weeks). 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 NCT00350779, 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 12 May 2017.