Type 2 Diabetes MellitusPhase 3NCT00722371
MK0431 and Pioglitazone Co-Administration Factorial Study in Patients With Type 2 Diabetes Mellitus (0431-102 AM2)
A Phase 3 study testing Sitagliptin phosphate, Pioglitazone hydrochloride and Metformin in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.
Trial summary
A study to evaluate the efficacy and safety of sitagliptin and pioglitazone co-administration in comparison with sitagliptin and pioglitazone monotherapy in patients with type 2 diabetes. 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 phosphate, Pioglitazone hydrochloride and Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,615 participants
- Where
- No sites listed yet
- Study dates
- 5 Sep 2008to 25 Mar 2011
- 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 is highly unlikely to conceive
- Patient meets one of the 3 categories is naïve to all antihyperglycemic agent (AHA) therapies, or is non-naïve based upon the patient's current diet, medical regimen and screening A1c patient is currently not on AHA with a screening A1c >=7.5 % and =<11.0 % patient is currently on either metformin pr sulfonylurea monotherapy with a screening A1c >=7.0 % and =<9.0 %
Who cannot join
- Patient has a history of type 1 diabetes mellitus or history of ketoacidosis or has C=peptide value of =<0.8 ng/mL
- Patient has previously been treated with insulin, thiazolidinedione (TZD) (rosiglitazone or pioglitazone), any Dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin, vildagliptin, or alogliptin), exenatide or has previously been in a clinical study with any DPP-4 inhibitor or incretin mimetic
- Patient is on a weight loss program and is not in the maintenance phase or has started a weight loss medication (e.g. orlistat or sibutramine) within the prior 8 weeks
- Patient has undergone surgery within the prior 30 days or has major surgery planned during the study
- Patient has a medical history of active liver disease including chronic active hepatitis B or C or symptomatic gallbladder disease including primary biliary cirrhosis
- Patient has received treatment with an investigational product within 12 weeks prior to Visit 1
About this study
Official title: A Multicenter, Randomized, Double-Blind Study of the Co-Administration of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control
A study to evaluate the efficacy and safety of sitagliptin and pioglitazone co-administration in comparison with sitagliptin and pioglitazone monotherapy in patients with type 2 diabetes.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Sitagliptin phosphate, Pioglitazone hydrochloride, Matching placebo to sitagliptin, Matching placebo to pioglitazone, 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.
Sitagliptin phosphateDrug
Also called Januvia, Tesavel, Xelevia, Ristaben
Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks.
Pioglitazone hydrochlorideDrug
Also called Actos
Pioglitazone 15 mg, 30 mg, or 45 mg tablets or capsules (blinded) orally once daily for 54 weeks. Participants randomized to receive pioglitazone 45 mg as monotherapy or in combination with sitagliptin were to start on pioglitazone 30 mg at Week 1 and undergo uptitration to pioglitazone 45 mg at Week 4.
Matching placebo to sitagliptinDrug
Matching placebo to sitagliptin orally once daily for 54 weeks.
Matching placebo to pioglitazoneDrug
Matching placebo to pioglitazone tablets or capsules orally once daily for 54 weeks.
MetforminDrug
Metformin 500 mg (open-label) was to be initiated as rescue therapy to participants not meeting specific glycemic goals. The dose of metformin may have been uptitrated and adjusted, at the discretion of the investigator, up to the maximum approved dose in the country of origin.
| Study group | Role | What they receive |
|---|---|---|
| Sitagliptin 100 mg | Experimental | Not described Receives: Drug: Sitagliptin phosphate; Drug: Matching placebo to pioglitazone; Drug: Metformin |
| Pioglitazone 15 mg | Experimental | Not described Receives: Drug: Pioglitazone hydrochloride; Drug: Matching placebo to sitagliptin; Drug: Metformin |
| Pioglitazone 30 mg | Experimental | Not described Receives: Drug: Pioglitazone hydrochloride; Drug: Matching placebo to sitagliptin; Drug: Metformin |
| Pioglitazone 45 mg | Experimental | Not described Receives: Drug: Pioglitazone hydrochloride; Drug: Matching placebo to sitagliptin; Drug: Metformin |
| Sitagliptin 100 mg/ Pioglitazone 15 mg | Experimental | Not described Receives: Drug: Sitagliptin phosphate; Drug: Pioglitazone hydrochloride; Drug: Metformin |
| Sitagliptin 100 mg/ Pioglitazone 30 mg | Experimental | Not described Receives: Drug: Sitagliptin phosphate; Drug: Pioglitazone hydrochloride; Drug: Metformin |
| Sitagliptin 100 mg/ Pioglitazone 45 mg | Experimental | Not described Receives: Drug: Sitagliptin phosphate; Drug: Pioglitazone hydrochloride; 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 (A1C) at Week 24
A1C represents the percentage of glycosylated hemoglobin.
Measured: Baseline and Week 24
Change From Baseline in A1C at Week 54
A1C represents the percentage of glycosylated hemoglobin.
Measured: Baseline and Week 54
Secondary outcomes (4)
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Measured: Baseline and Week 24
Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 24
PMG was measured using the Meal Tolerance Test (MTT).
Measured: Baseline and Week 24
Change From Baseline in FPG at Week 54
Measured: Baseline and Week 54
Change From Baseline in 2-Hour PMG at Week 54
PMG was measured using the Meal Tolerance Test (MTT).
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.
- First posted25 Jul 2008 (estimated)
- Study start5 Sep 2008
- Primary completion26 Oct 2010
- Study completion25 Mar 2011
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
- 1,615 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00722371
- Sponsor's protocol ID
- 0431-102
- Other IDs
- 2008_522
- Status last verified
- Apr 2017
- First submitted
- 22 Jul 2008
- 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
Henry RR, Staels B, Fonseca VA, Chou MZ, Teng R, Golm GT, Langdon RB, Kaufman KD, Steinberg H, Goldstein BJ. Efficacy and safety of initial combination treatment with sitagliptin and pioglitazone--a factorial study. Diabetes Obes Metab. 2014 Mar;16(3):223-30. doi: 10.1111/dom.12194. Epub 2013 Aug 29.
PubMed 23909985
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 Multicenter, Randomized, Double-Blind Study of the Co-Administration of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control
- ClinicalTrials.gov ID
- NCT00722371
- Acronym / sponsor ID
- 0431-102
- Conditions
- Type 2 Diabetes Mellitus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,615 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 5 Sep 2008 (actual)
- Primary completion
- 26 Oct 2010 (actual)
- Study completion
- 25 Mar 2011 (actual)
- First posted
- 25 Jul 2008 (estimated)
- Results
- Posted 17 Oct 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to evaluate the efficacy and safety of sitagliptin and pioglitazone co-administration in comparison with sitagliptin and pioglitazone monotherapy in patients with type 2 diabetes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Sitagliptin 100 mg | Experimental | Drug: Sitagliptin phosphate, Drug: Matching placebo to pioglitazone, Drug: Metformin |
| Pioglitazone 15 mg | Experimental | Drug: Pioglitazone hydrochloride, Drug: Matching placebo to sitagliptin, Drug: Metformin |
| Pioglitazone 30 mg | Experimental | Drug: Pioglitazone hydrochloride, Drug: Matching placebo to sitagliptin, Drug: Metformin |
| Pioglitazone 45 mg | Experimental | Drug: Pioglitazone hydrochloride, Drug: Matching placebo to sitagliptin, Drug: Metformin |
| Sitagliptin 100 mg/ Pioglitazone 15 mg | Experimental | Drug: Sitagliptin phosphate, Drug: Pioglitazone hydrochloride, Drug: Metformin |
| Sitagliptin 100 mg/ Pioglitazone 30 mg | Experimental | Drug: Sitagliptin phosphate, Drug: Pioglitazone hydrochloride, Drug: Metformin |
| Sitagliptin 100 mg/ Pioglitazone 45 mg | Experimental | Drug: Sitagliptin phosphate, Drug: Pioglitazone hydrochloride, Drug: Metformin |
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 is highly unlikely to conceive
- Patient meets one of the 3 categories is naïve to all antihyperglycemic agent (AHA) therapies, or is non-naïve based upon the patient's current diet, medical regimen and screening A1c patient is currently not on AHA with a screening A1c >=7.5 % and =<11.0 % patient is currently on either metformin pr sulfonylurea monotherapy with a screening A1c >=7.0 % and =<9.0 %
Key exclusion criteria (6 listed)
- Patient has a history of type 1 diabetes mellitus or history of ketoacidosis or has C=peptide value of =<0.8 ng/mL
- Patient has previously been treated with insulin, thiazolidinedione (TZD) (rosiglitazone or pioglitazone), any Dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin, vildagliptin, or alogliptin), exenatide or has previously been in a clinical study with any DPP-4 inhibitor or incretin mimetic
- Patient is on a weight loss program and is not in the maintenance phase or has started a weight loss medication (e.g. orlistat or sibutramine) within the prior 8 weeks
- Patient has undergone surgery within the prior 30 days or has major surgery planned during the study
- Patient has a medical history of active liver disease including chronic active hepatitis B or C or symptomatic gallbladder disease including primary biliary cirrhosis
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 |
|---|---|---|
| Sitagliptin phosphateAlso: Januvia, Tesavel, Xelevia, RistabenSitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks. | Drug | Sitagliptin 100 mg, Sitagliptin 100 mg/ Pioglitazone 15 mg, Sitagliptin 100 mg/ Pioglitazone 30 mg, Sitagliptin 100 mg/ Pioglitazone 45 mg |
| Pioglitazone hydrochlorideAlso: ActosPioglitazone 15 mg, 30 mg, or 45 mg tablets or capsules (blinded) orally once daily for 54 weeks. Participants randomized to receive pioglitazone 45 mg as monotherapy or in combination with sitagliptin were to start on pioglitazone 30 mg at Week 1 and undergo uptitration to pioglitazone 45 mg at Week 4. | Drug | Pioglitazone 15 mg, Pioglitazone 30 mg, Pioglitazone 45 mg, Sitagliptin 100 mg/ Pioglitazone 15 mg, Sitagliptin 100 mg/ Pioglitazone 30 mg, Sitagliptin 100 mg/ Pioglitazone 45 mg |
| Matching placebo to sitagliptinMatching placebo to sitagliptin orally once daily for 54 weeks. | Drug | Pioglitazone 15 mg, Pioglitazone 30 mg, Pioglitazone 45 mg |
| Matching placebo to pioglitazoneMatching placebo to pioglitazone tablets or capsules orally once daily for 54 weeks. | Drug | Sitagliptin 100 mg |
| MetforminMetformin 500 mg (open-label) was to be initiated as rescue therapy to participants not meeting specific glycemic goals. The dose of metformin may have been uptitrated and adjusted, at the discretion of the investigator, up to the maximum approved dose in the country of origin. | Drug | Pioglitazone 15 mg, Pioglitazone 30 mg, Pioglitazone 45 mg, Sitagliptin 100 mg, Sitagliptin 100 mg/ Pioglitazone 15 mg, Sitagliptin 100 mg/ Pioglitazone 30 mg, Sitagliptin 100 mg/ Pioglitazone 45 mg |
Primary outcome
Change From Baseline in Hemoglobin A1C (A1C) at Week 24
Time frame: Baseline and Week 24
A1C represents the percentage of glycosylated hemoglobin.
Change From Baseline in A1C at Week 54
Time frame: Baseline and Week 54
A1C represents the percentage of glycosylated hemoglobin.
4 secondary outcomes
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Time frame: Baseline and Week 24
Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 24
Time frame: Baseline and Week 24
Change From Baseline in FPG at Week 54
Time frame: Baseline and Week 54
Change From Baseline in 2-Hour PMG at Week 54
Time frame: Baseline and Week 54
Results and safety
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 23909985Henry RR, Staels B, Fonseca VA, Chou MZ, Teng R, Golm GT, Langdon RB, Kaufman KD, Steinberg H, Goldstein BJ. Efficacy and safety of initial combination treatment with sitagliptin and pioglitazone--a factorial study. Diabetes Obes Metab. 2014 Mar;16(3):223-30. doi: 10.1111/dom.12194. Epub 2013 Aug 29.
- 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
Related trials for Type 2 Diabetes Mellitus
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
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
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
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 phosphate, Pioglitazone hydrochloride 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 6 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. 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 17 Oct 2011). 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 (A1C) at Week 24 (time frame: Baseline and Week 24). 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 NCT00722371, 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.