Type 2 Diabetes Mellitus (T2DM)Phase 1NCT00511108

Sitagliptin and Pioglitazone Mechanism of Action Study in Type 2 Diabetes Mellitus (0431-061)

A Phase 1 study testing Comparator: sitagliptin phosphate and Comparator: pioglitazone in people with Type 2 Diabetes Mellitus (T2DM), 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, efficacy and mechanism of action of sitagliptin alone and in combination with pioglitazone, in patients with type 2 diabetes mellitus who have inadequate glycemic (blood sugar) control. Read more about this study

Who is it for?: Ages 30 to 65 years
Conditions the study is for: Type 2 Diabetes Mellitus (T2DM)
What is being tested?: Comparator: sitagliptin phosphate and Comparator: pioglitazone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 211 participants
Where: No sites listed yet
Study dates: 11 Jul 2007to 24 Feb 2009
Phase: Phase 1
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 30 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient has type 2 diabetes mellitus
Male
Female that is highly unlikely to become pregnant
Patient is not on an antihyperglycemic agent (AHA) (hemoglobin A1c [A1C] 7-10%) or on oral single AHA or low-dose combination therapy (A1C 6.5-9.0%)

Who cannot join

Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis
Patient has required insulin therapy within the past 12 weeks
Patient is on or has been taking a Peroxisome Proliferator-Activated Receptor-gamma (PPAR -gamma) agent (i.e. Thiazolidinediones [TZDs]) within the prior 12 weeks of the screening visit.

About this study

Official title: A Phase I Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Study the Safety, Efficacy, and Mechanism of Action of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Diet and Exercise

Conditions: Type 2 Diabetes Mellitus (T2DM)
Being tested: Comparator: sitagliptin phosphate, Comparator: pioglitazone, Comparator: placebo to pioglitazone, Comparator: placebo to sitagliptin
Keywords: Type 2 Diabetes Mellitus (T2DM)
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.

Comparator: sitagliptin phosphateDrug
sitagliptin phosphate 100 mg as oral tablets. Each patient will be administered 1 tablet once daily.
Comparator: pioglitazoneDrug
pioglitazone 30 mg will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.
Comparator: placebo to pioglitazoneDrug
pioglitazone 30 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.
Comparator: placebo to sitagliptinDrug
sitagliptin phosphate 100 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.

Study groups in NCT00511108
Study group	Role	What they receive
1	Experimental	Arm 1: drug Receives: Drug: Comparator: sitagliptin phosphate; Drug: Comparator: placebo to pioglitazone
2	Active comparator	Arm 2: active comparator Receives: Drug: Comparator: pioglitazone; Drug: Comparator: placebo to sitagliptin
3	Experimental	Arm 3: drug + active comparator Receives: Drug: Comparator: sitagliptin phosphate; Drug: Comparator: pioglitazone
4	Placebo comparator	Arm 4: placebo comparator Receives: Drug: Comparator: placebo to pioglitazone; Drug: Comparator: placebo to sitagliptin

What is being measured

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

Change From Baseline in Glucagon 3-hour Total Area Under the Curve (AUC) After 12 Weeks of Treatment
Glucagon concentration was measured at 9 points during an Meal Tolerance Test (MTT), at times -10, 0, 10, 20, 30, 60, 90, 120, and 180 minutes. Total AUC was calculated over 3 hours including all sample points starting from 0 minutes using the trapezoid method. The change from baseline reflects Week 12 total AUC minus the Week 0 total AUC.
Measured: Baseline and 12 weeks
Percent Change From Baseline in Index of Static Beta-cell Sensitivity to Glucose After 12 Weeks of Treatment
Static sensitivity is a measure of the effect of glucose on beta cell secretion and is the ratio between the insulin secretion rate and glucose concentration above the threshold level at steady state.
Percent change from baseline was calculated as the difference between index of static sensitivities at Week 12 and at baseline with respect to the index of static sensitivity at baseline times 100.
Measured: Baseline and 12 weeks

Secondary outcomes (1)

Change From Baseline in Glucose 5-hour Total AUC After 12 Weeks of Treatment
Glucose concentration was measured at 11 points during an Meal Tolerance Test (MTT), at times -10, 0, 10, 20, 30, 60, 90, 120, 180, 240, 300 minutes. Total AUC was calculated over 5 hours including all sample points starting from 0 minutes using the trapezoid method. The change from baseline reflects Week 12 total AUC minus the Week 0 total AUC.
Measured: Baseline and 12 weeks

Timeline

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

11 Jul 200724 Feb 2009

First posted3 Aug 2007 (estimated)
Study start11 Jul 2007
Primary completion24 Feb 2009
Study completion24 Feb 2009

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 Mellitus (T2DM)Studies 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 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 211 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00511108
Sponsor's protocol ID: 0431-061
Other IDs: MK0431-061, 2007_530
Status last verified: Apr 2017
First submitted: 2 Aug 2007
Last updated: 12 May 2017
Results posted: Yes, on ClinicalTrials.gov
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

Alba M, Ahren B, Inzucchi SE, Guan Y, Mallick M, Xu L, O'Neill EA, Williams-Herman DE, Kaufman KD, Goldstein BJ. Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function. Diabetes Obes Metab. 2013 Dec;15(12):1101-10. doi: 10.1111/dom.12145. Epub 2013 Jul 19.
PubMed 23782502

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 (T2DM) 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 I Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Study the Safety, Efficacy, and Mechanism of Action of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Diet and Exercise
ClinicalTrials.gov ID: NCT00511108
Acronym / sponsor ID: 0431-061
Conditions: Type 2 Diabetes Mellitus (T2DM)
Keywords: Type 2 Diabetes Mellitus (T2DM)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 211 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 11 Jul 2007 (actual)
Primary completion: 24 Feb 2009 (actual)
Study completion: 24 Feb 2009 (actual)
First posted: 3 Aug 2007 (estimated)
Results: Posted 5 Mar 2010

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: 4

Arm	Type	Receives
1	Experimental	Drug: Comparator: sitagliptin phosphate, Drug: Comparator: placebo to pioglitazoneArm 1: drug
2	Active comparator	Drug: Comparator: pioglitazone, Drug: Comparator: placebo to sitagliptinArm 2: active comparator
3	Experimental	Drug: Comparator: sitagliptin phosphate, Drug: Comparator: pioglitazoneArm 3: drug + active comparator
4	Placebo comparator	Drug: Comparator: placebo to pioglitazone, Drug: Comparator: placebo to sitagliptinArm 4: placebo comparator

Who may qualify

Ages: 30 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Patient has type 2 diabetes mellitus
Male
Female that is highly unlikely to become pregnant
Patient is not on an antihyperglycemic agent (AHA) (hemoglobin A1c [A1C] 7-10%) or on oral single AHA or low-dose combination therapy (A1C 6.5-9.0%)

Key exclusion criteria (3 listed)

Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis
Patient has required insulin therapy within the past 12 weeks
Patient is on or has been taking a Peroxisome Proliferator-Activated Receptor-gamma (PPAR -gamma) agent (i.e. Thiazolidinediones [TZDs]) within the prior 12 weeks of the screening visit.

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
Comparator: sitagliptin phosphatesitagliptin phosphate 100 mg as oral tablets. Each patient will be administered 1 tablet once daily.	Drug	1, 3
Comparator: pioglitazonepioglitazone 30 mg will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.	Drug	2, 3
Comparator: placebo to pioglitazonepioglitazone 30 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.	Drug	1, 4
Comparator: placebo to sitagliptinsitagliptin phosphate 100 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.	Drug	2, 4

Primary outcome

Change From Baseline in Glucagon 3-hour Total Area Under the Curve (AUC) After 12 Weeks of Treatment
Time frame: Baseline and 12 weeks
Glucagon concentration was measured at 9 points during an Meal Tolerance Test (MTT), at times -10, 0, 10, 20, 30, 60, 90, 120, and 180 minutes. Total AUC was calculated over 3 hours including all sample points starting from 0 minutes using the trapezoid method. The change from baseline reflects Week 12 total AUC minus the Week 0 total AUC.
Percent Change From Baseline in Index of Static Beta-cell Sensitivity to Glucose After 12 Weeks of Treatment
Time frame: Baseline and 12 weeks
Static sensitivity is a measure of the effect of glucose on beta cell secretion and is the ratio between the insulin secretion rate and glucose concentration above the threshold level at steady state. Percent change from baseline was calculated as the difference between index of static sensitivities at Week 12 and at baseline with respect to the index of static sensitivity at baseline times 100.

1 secondary outcome

Change From Baseline in Glucose 5-hour Total AUC After 12 Weeks of Treatment
Time frame: Baseline and 12 weeks

Results and safety

Results posted to the registry on 5 Mar 2010, 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	52	46
Pioglitazone 30 mg	54	52
Sitagliptin 100 mg + Pioglitazone 30 mg	52	47
Placebo	53	48

Primary outcome: Change From Baseline in Glucagon 3-hour Total Area Under the Curve (AUC) After 12 Weeks of Treatment

Time frame: Baseline and 12 weeks. Least squares mean (95% Confidence Interval). Unit: pg*hr/mL

Measure	Sitagliptin 100 mg n = 48	Pioglitazone 30 mg n = 47	Sitagliptin 100 mg + Pioglitazone 30 mg n = 42	Placebo n = 39
Value	-17.2 (-30.1 to -4.2)	-4.9 (-18.1 to 8.3)	-29.8 (-43.6 to -16.1)	12.5 (-1.9 to 26.9)

Sitagliptin 100 mg vs Placebo: Mean Difference (Net): -29.7 (95% CI -48.7 to -10.6), p = 0.002, ANCOVA

Population analysed: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. For FAS patients with no data at Week 12, the last observed measurement was carried forward to Week 12.

Primary outcome: Percent Change From Baseline in Index of Static Beta-cell Sensitivity to Glucose After 12 Weeks of Treatment

Time frame: Baseline and 12 weeks. Least squares mean (95% Confidence Interval). Unit: Percent Change

Measure	Sitagliptin 100 mg n = 38	Pioglitazone 30 mg n = 34	Sitagliptin 100 mg + Pioglitazone 30 mg n = 27	Placebo n = 33
Value	71.5 (46.8 to 100.3)	27.0 (7.8 to 49.7)	125.2 (87.2 to 171.0)	-2.3 (-17.4 to 15.5)

Sitagliptin 100 mg vs Placebo: Geometric Mean Difference: 73.8 (95% CI 44.2 to 104.4), p <0.001, ANCOVA

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Weeks 0-12. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sitagliptin 100 mg	1 of 52 (1.9%)	3 of 52 (5.8%)	Not reported
Pioglitazone 30 mg	0 of 54 (0%)	3 of 54 (5.6%)	Not reported
Sitagliptin 100 mg + Pioglitazone 30 mg	1 of 52 (1.9%)	0 of 52 (0%)	Not reported
Placebo	0 of 53 (0%)	9 of 53 (17%)	Not reported

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.
Results publication: PubMed 23782502Alba M, Ahren B, Inzucchi SE, Guan Y, Mallick M, Xu L, O'Neill EA, Williams-Herman DE, Kaufman KD, Goldstein BJ. Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function. Diabetes Obes Metab. 2013 Dec;15(12):1101-10. doi: 10.1111/dom.12145. Epub 2013 Jul 19.
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 1 study testing Comparator: sitagliptin phosphate and Comparator: pioglitazone in people with Type 2 Diabetes Mellitus (T2DM), 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 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 5 Mar 2010). 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 Glucagon 3-hour Total Area Under the Curve (AUC) After 12 Weeks of Treatment (time frame: Baseline and 12 weeks). The study lists 2 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 NCT00511108, 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.