Trial Outcomes & Findings for A Study to Assess the Safety and Tolerability of Sitagliptin/Simvastatin Fixed-dose Combination (FDC) in Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-312) (NCT NCT01702298)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

42 participants

Primary outcome timeframe

Baseline and Week 6

Results posted on

2018-08-24

Participant Flow

Participant milestones

Participant milestones
Measure	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).
Overall Study STARTED	42
Overall Study COMPLETED	41
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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).
Overall Study Withdrawal by Subject	1

Baseline Characteristics

A Study to Assess the Safety and Tolerability of Sitagliptin/Simvastatin Fixed-dose Combination (FDC) in Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-312)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin 100 mg/Simvastatin 40 mg FDC n=42 Participants 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).
Age, Continuous	48.3 Years STANDARD_DEVIATION 7.1 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants
Fasting Plasma Glucose (FPG)	159.3 mg/dL STANDARD_DEVIATION 40.9 • n=5 Participants
Low-density lipoprotein cholesterol (LDL-C)	109.6 mg/dL STANDARD_DEVIATION 27.2 • n=5 Participants
Total Cholesterol (TC)	195.2 md/dL STANDARD_DEVIATION 36.4 • n=5 Participants
(Non-High-Density Lipoprotein Cholesterol (non-HDL-C)	152.0 mg/dL STANDARD_DEVIATION 37.9 • n=5 Participants
Triglycerides (TG)	225.3 mg/dL STANDARD_DEVIATION 152.5 • n=5 Participants
High-Density Lipoprotein Cholesterol (HDL-C)	43.1 mg/dL STANDARD_DEVIATION 11.9 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg/Simvastatin 40 mg FDC n=42 Participants 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).
Change From Baseline in Fasting Plasma Glucose (FPG)	-27.6 mg/dL 95% Confidence Interval 58.4 • Interval -46.0 to -9.3

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg/Simvastatin 40 mg FDC n=42 Participants 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).
Percentage of Participants Who Experienced at Least One Adverse Event	9.5 Percentage of participants Interval 2.7 to 22.6

PRIMARY outcome

Timeframe: Up to 6 weeks

Population: All participants treated population defined as all enrolled participants who received at least one dose of study treatment.

Participants who were discontinued from study drug due to an adverse event during the 6 weeks of treatment.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg/Simvastatin 40 mg FDC n=42 Participants 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).
Number of Participants Who Discontinued Study Drug Due to an Adverse Event	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg/Simvastatin 40 mg FDC n=41 Participants 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).
Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)	-46.5 Percent change 95% Confidence Interval 17.0 • Interval -51.9 to -41.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg/Simvastatin 40 mg FDC n=41 Participants 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).
Change From Baseline in Total Cholesterol (TC)	-33.7 Percent change Interval -37.3 to -30.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg/Simvastatin 40 mg FDC n=41 Participants 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).
Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C)	-43.1 Percent change Interval -47.4 to -38.9

SECONDARY outcome

Timeframe: 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.

Change from baseline in TG was measured as a percent change from baseline at Week 6 (median and distribution free 95% confidence interval).

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg/Simvastatin 40 mg FDC n=41 Participants 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).
Change From Baseline in Triglycerides (TG)	-31.8 Percent change 95% Confidence Interval 26.3 • Interval -41.1 to -18.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg/Simvastatin 40 mg FDC n=41 Participants 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).
Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)	1.3 Percent change Interval -5.0 to 7.5

Adverse Events

Sitagliptin 100 mg/Simvastatin 40 mg FDC

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Sitagliptin 100 mg/Simvastatin 40 mg FDC n=42 participants at risk 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).
Metabolism and nutrition disorders Hypoglycemia	7.1% 3/42 • Number of events 4 • Up to 8 weeks

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER