Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to examine the safety and tolerability of sitagliptin 100 mg/simvastatin 40 mg FDC (MK-0431D) in Vietnamese participants with type 2 diabetes mellitus with inadequate glycemic control on metformin.
Interventions
DRUGSitagliptin 100 mg/simvastatin 40 mg FDC
Sitagliptin 100 mg/simvastatin 40 mg FDC tablet administered once daily in the evening for 6 weeks
DRUGMetformin
Participants will continue pre-study dose of metformin tablet(s) \>=1000 per day
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Has type 2 diabetes mellitus * Male, or female who is not of reproductive potential or if of reproductive potential agrees to abstain or use (or have their partner use) two acceptable methods of birth control during the study and for 14 days after the last dose of study drug * Currently on metformin monotherapy (\>=1000 mg per day) for at least 4 weeks prior to study participation * Not on statin therapy or other lipid-lowering agent for at least 6 weeks prior to study participation
Exclusion criteria
* History of type 1 diabetes mellitus or a history of ketoacidosis * History of 2 or more episodes of hypoglycemia resulting in seizure, coma or loss of consciousness over the past 3 months * On a thiazolidinedione (TZD) within the past 12 weeks * Has been treated with a statin or other lipid-lowering agent within 6 weeks prior to study participation * Is on or likely to require treatment with a prohibited medication (itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, danazol, amiodarone, verapamil, diltiazem, amlodipine, ranolazine, niacin) * Intends to consume \>1.2 liters of grapefruit juice per day during the study * Is on or likely to require treatment for \>=2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted) * 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 prior to study participation * Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study * History of myopathy or rhabdomyolysis with any statin * History of myocardial infarction, unstable or stable angina, angioplasty, bypass surgery, myocardial ischemia, peripheral artery disease, abdominal aortic aneurysm, transient ischemic attacks, stroke of carotid origin or \>50% obstruction of a carotid artery * Diagnosis of congestive heart failure with New York Heart Association (NYHA) Class III or IV cardiac status * History of active liver disease (other than non-alcoholic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease * Chronic progressive neuromuscular disorder * Human immunodeficiency virus (HIV) * Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) * Currently being treated for hyperthyroidism or is on thyroid hormone replacement therapy and has not been on a stable dose for at least 6 weeks * History of malignancy \<=5 years prior to study participation, except for basal cell or squamous cell skin cancer or in situ cervical cancer * Positive urine pregnancy test * Pregnant or breastfeeding, or is expecting to conceive or donate eggs during the study, including 14 days following the last dose of study drug * User of recreational or illicit drugs or has had a recent history of drug abuse * Routinely consumes \>2 alcoholic drinks per day or \>14 alcoholic drinks per week, or engages in binge drinking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline and Week 6 | Change from baseline in FPG at Week 6 based on longitudinal data analysis (LDA) model including both baseline and post-baseline measurements as response variable and term time. |
| Percentage of Participants Who Experienced at Least One Adverse Event | Up to 8 weeks (including 14 days after final dose of study drug) | An 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. |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to 6 weeks | Participants who were discontinued from study drug due to an adverse event during the 6 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Baseline and Week 6 | Change from baseline in LDL-C was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time. |
| Change From Baseline in Total Cholesterol (TC) | Baseline and Week 6 | Change from baseline in TC was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time. |
| Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) | Baseline and Week 6 | Change from baseline in non-HDL-C was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time. |
| Change From Baseline in Triglycerides (TG) | Baseline and Week 6 | Change from baseline in TG was measured as a percent change from baseline at Week 6 (median and distribution free 95% confidence interval). |
| Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) | Baseline and Week 6 | Change from baseline in HDL-C was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 100 mg/Simvastatin 40 mg FDC Sitagliptin 100 mg/simvastatin 40 mg FDC once daily in the evening for 6 weeks. Participants continued on their pre-study dose of metformin (\>=1000 mg per day). | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Sitagliptin 100 mg/Simvastatin 40 mg FDC |
|---|---|
| Age, Continuous | 48.3 Years STANDARD_DEVIATION 7.1 |
| Fasting Plasma Glucose (FPG) | 159.3 mg/dL STANDARD_DEVIATION 40.9 |
| High-Density Lipoprotein Cholesterol (HDL-C) | 43.1 mg/dL STANDARD_DEVIATION 11.9 |
| Low-density lipoprotein cholesterol (LDL-C) | 109.6 mg/dL STANDARD_DEVIATION 27.2 |
| (Non-High-Density Lipoprotein Cholesterol (non-HDL-C) | 152.0 mg/dL STANDARD_DEVIATION 37.9 |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 23 Participants |
| Total Cholesterol (TC) | 195.2 md/dL STANDARD_DEVIATION 36.4 |
| Triglycerides (TG) | 225.3 mg/dL STANDARD_DEVIATION 152.5 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 42 |
| serious Total, serious adverse events | 0 / 42 |
Outcome results
Primary
Change From Baseline in Fasting Plasma Glucose (FPG)
Change from baseline in FPG at Week 6 based on longitudinal data analysis (LDA) model including both baseline and post-baseline measurements as response variable and term time.
Time frame: Baseline and Week 6
Population: Full analysis set (FAS) defined as all participants who took at least one dose of study medication and had at least one baseline or post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin 100 mg/Simvastatin 40 mg FDC | Change From Baseline in Fasting Plasma Glucose (FPG) | -27.6 mg/dL | 95% Confidence Interval 58.4 |
Primary
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Participants who were discontinued from study drug due to an adverse event during the 6 weeks of treatment.
Time frame: Up to 6 weeks
Population: All participants treated population defined as all enrolled participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin 100 mg/Simvastatin 40 mg FDC | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
Primary
Percentage of Participants Who Experienced at Least One Adverse Event
An 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.
Time frame: Up to 8 weeks (including 14 days after final dose of study drug)
Population: All participants treated population defined as all enrolled participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin 100 mg/Simvastatin 40 mg FDC | Percentage of Participants Who Experienced at Least One Adverse Event | 9.5 Percentage of participants |
Secondary
Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
Change from baseline in HDL-C was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time.
Time frame: Baseline and Week 6
Population: FAS defined as all participants who took at least one dose of study medication and had both baseline and post-baseline measurements. One participant, who had no on-treatment data, was excluded from the FAS for the LDA analysis of HDL-C.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg/Simvastatin 40 mg FDC | Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) | 1.3 Percent change |
Secondary
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
Change from baseline in LDL-C was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time.
Time frame: Baseline and Week 6
Population: FAS defined as all participants who took at least one dose of study medication and had both baseline and post-baseline measurements. One participant, who had no on-treatment data, was excluded from the FAS for the LDA analysis of LDL-C.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin 100 mg/Simvastatin 40 mg FDC | Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | -46.5 Percent change | 95% Confidence Interval 17 |
Secondary
Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C)
Change from baseline in non-HDL-C was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time.
Time frame: Baseline and Week 6
Population: FAS defined as all participants who took at least one dose of study medication and had both baseline and post-baseline measurements. One participant, who had no on-treatment data, was excluded from the FAS for the LDA analysis of non-HDL-C.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg/Simvastatin 40 mg FDC | Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) | -43.1 Percent change |
Secondary
Change From Baseline in Total Cholesterol (TC)
Change from baseline in TC was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time.
Time frame: Baseline and Week 6
Population: FAS defined as all participants who took at least one dose of study medication and had both baseline and post-baseline measurements.~One participant, who had no on-treatment data, was excluded from the FAS for the LDA analysis of TC.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg/Simvastatin 40 mg FDC | Change From Baseline in Total Cholesterol (TC) | -33.7 Percent change |
Secondary
Change From Baseline in Triglycerides (TG)
Change from baseline in TG was measured as a percent change from baseline at Week 6 (median and distribution free 95% confidence interval).
Time frame: Baseline and Week 6
Population: FAS defined as all participants who took at least one dose of study medication and had both baseline and post-baseline measurements. One participant, who had no on-treatment data, was excluded from the FAS.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Sitagliptin 100 mg/Simvastatin 40 mg FDC | Change From Baseline in Triglycerides (TG) | -31.8 Percent change | 95% Confidence Interval 26.3 |