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Type 2 Diabetes MellitusPhase 3NCT01678820

A Study of the Efficacy and Safety of MK-0431D (a Fixed-dose Combination of Sitagliptin and Simvastatin) for the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-266)

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

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to assess the efficacy and safety of sitagliptin/simvastatin fixed-dose combination (FDC) in participants with T2DM who have inadequate glycemic control while on metformin monotherapy. Read more about this study

Who is it for?
Ages 18 to 79 years
Conditions the study is for
Type 2 Diabetes Mellitus
What is being tested?
Sitagliptin/Simvastatin FDC, Sitagliptin and Simvastatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
299 participants
Where
No sites listed yet
Study dates
10 Oct 2012to 1 Nov 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 18 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • has T2DM
  • (1) Male; (2) female not of reproductive potential; or (3) female of reproductive potential who agrees to remain abstinent or use alone or in conjunction with their partner 2 methods of contraception to prevent pregnancy during the study and for 14 days after the last dose of study drug
  • is currently on metformin monotherapy at a daily dose of at least 1500 mg for at least 10 weeks
  • is not on a lipid-lowering agent for at least 6 weeks prior to entering the study

Who cannot join

  • has history of type 1 diabetes mellitus (T1DM), or a history of ketoacidosis or possibly has T1DM
  • has been on a thiazolidinedione (TZD) within the previous 16 weeks
  • has been treated with a statin or other lipid-lowering agent (including over-the-counter [OTC] supplements) within the previous 6 weeks
  • currently participating in or has participated in another clinical study within the past 12 weeks
  • intends to consume >1.2 liters of grapefruit juice daily during the study
  • is on or likely to require treatment for at least 2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)
Show all 19Show fewer
  • intolerance or hypersensitivity to sitagliptin, simvastatin, metformin or glimepiride
  • is on a weight loss program and not in the maintenance phase or has started a weight loss medication or has undergone bariatric surgery in the previous 12 months
  • has undergone a surgical procedure in the past 4 weeks or planned major surgery during the study
  • has symptomatic hyperglycemia that requires immediate initiation, adjustment, or addition of antihyperglycemic therapy
  • has a history of myopathy or rhabdomyolysis with any statin
  • has cardiovascular disease, a diagnosis of congestive heart failure, or uncontrolled high blood pressure
  • has a history of active liver disease
  • has chronic progressive neuromuscular disorder, human immunodeficiency virus (HIV), hematological disorder, or uncontrolled endocrine or metabolic 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 in the previous 5 years (excluding adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer)
  • is pregnant or breast feeding, or is expecting to conceive or donate eggs during the course of the study, including 14 days after the last dose of study drug
  • is a user of recreational or illicit drugs or has had a recent history of drug abuse
  • consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking

About this study

Official title: A Phase III, Randomized, Double-blind, Clinical Trial to Study the Efficacy and Safety of MK-0431D (a Fixed-dose Combination [FDC] of Sitagliptin and Simvastatin) for the Treatment of Patients With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy

The purpose of this study is to assess the efficacy and safety of sitagliptin/simvastatin fixed-dose combination (FDC) in participants with T2DM who have inadequate glycemic control while on metformin monotherapy. The primary hypothesis of this study is that after 16 weeks of therapy, the mean change from baseline in hemoglobin A1C (A1C) in participants treated with sitagliptin/simvastatin FDC is non-inferior compared to sitagliptin alone.

Being tested
Sitagliptin/Simvastatin FDC, Sitagliptin, Simvastatin, Placebo to sitagliptin, Placebo to simvastatin
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/Simvastatin FDCDrug

    Also called MK-0431D, Juvisync™, Juvicor®

    Sitagliptin 100 mg/Simvastatin 40 mg fixed-dose combination tablet

  • SitagliptinDrug

    Also called MK-0431, Januvia®, Tesavel®, Xelevia®

    Sitagliptin 100 mg tablet

  • SimvastatinDrug

    Also called MK-0733, Zocor®

    Simvastatin 40 mg tablet

  • Placebo to sitagliptinDrug

    Matching placebo to sitagliptin 100 mg tablet

  • Placebo to simvastatinDrug

    Matching placebo to simvastatin 40 mg tablet

  • Placebo to Sitagliptin/Simvastatin FDCDrug

    Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet

  • MetforminDrug

    Also called Fortamet®, Glucophage®, Glucophage® XR, Glumetza®

    Participants will continue on their stable, pre-screening metformin daily dose of >= 1500 mg for at least 12 weeks prior to randomization and during the study

  • GlimepirideDrug

    Also called Amaryl®, Glimy

    Following randomization, participants requiring glycemic rescue may receive open-label glimepiride initiated at a dose of 1 mg/day or 2 mg/day which may be up-titrated to 6 mg/day taken once daily with breakfast or the first main meal of the day.

Study groups in NCT01678820
Study groupRoleWhat they receive
Sitagliptin/Simvastatin FDCExperimentalSitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Receives: Drug: Sitagliptin/Simvastatin FDC; Drug: Placebo to sitagliptin; Drug: Placebo to simvastatin; Drug: Metformin; Drug: Glimepiride
SitagliptinActive comparatorSitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Receives: Drug: Sitagliptin; Drug: Placebo to simvastatin; Drug: Placebo to Sitagliptin/Simvastatin FDC; Drug: Metformin; Drug: Glimepiride
SimvastatinActive comparatorSimvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Receives: Drug: Simvastatin; Drug: Placebo to sitagliptin; Drug: Placebo to Sitagliptin/Simvastatin FDC; Drug: Metformin; Drug: Glimepiride

What is being measured

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

  1. Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin)

    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. sitagliptin. Results for simvastatin are presented below under secondary outcome measures.

    Measured: Baseline and Week 16

  2. Number of Participants Who Experienced at Least One Adverse Event (AE)

    Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.

    Measured: Up to 16 weeks for non-serious AEs, up to 18 weeks for serious AEs

  3. Number of Participants Who Discontinued Study Drug Due to an Adverse Event

    Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.

    Measured: Up to 16 weeks

Secondary outcomes (10)

  1. Change From Baseline in A1C at Week 16 (Sitagliptin/Simvastatin FDC vs. Simvastatin)

    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. simvastatin. Results for sitagliptin are presented above under primary outcome measures.

    Measured: Baseline and Week 16

  2. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16

    Change from baseline reflects the Week 16 value minus the Week 0 value.

    Measured: Baseline and Week 16

  3. Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 16

    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

    Measured: Baseline and Week 16

  4. Percent Change From Baseline in Total Cholesterol (TC) at Week 16

    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

    Measured: Baseline and Week 16

  5. Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16

    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

    Measured: Baseline and Week 16

  6. Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16

    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

    Measured: Baseline and Week 16

  7. Percent Change From Baseline in Triglycerides (TG) at Week 16

    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

    Measured: Baseline and Week 16

  8. Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 16

    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

    Measured: Baseline and Week 16

  9. Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16

    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

    Measured: Baseline and Week 16

  10. Percentage of Participants With A1C Level <7% at Week 16

    Percentage of participants achieving glycemic goal (A1C <7%) after 16 weeks of treatment. Data as observed.

    Measured: Week 16

Timeline

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

  1. First posted5 Sep 2012 (estimated)
  2. Study start10 Oct 2012
  3. Primary completion1 Nov 2013
  4. Study completion1 Nov 2013

Why it stopped: Merck terminated the study for business reasons in November 2013.

Resources

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
299 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01678820
Sponsor's protocol ID
0431D-266
Status last verified
Jul 2018
First submitted
31 Aug 2012
Last updated
24 Aug 2018
Data monitoring committee
No
Individual data sharing
Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sitagliptin/Simvastatin FDC, Sitagliptin and Simvastatin 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 19 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: stopped early, as of the sponsor's last update on 24 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. 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 22 Oct 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 in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin) (time frame: Baseline and Week 16). 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 NCT01678820.

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 24 Aug 2018.

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