Trial Outcomes & Findings for A Study of the Effects of Co-Administration of Sitagliptin (MK-0431) and Metformin on Incretin Hormone Concentrations (MK-0431-110) (NCT NCT00830076)

Last Updated: 2017-05-15

Results Overview

Meal was given 2 hours postdose. Blood samples for determination of active GLP-1 concentration were collected (4 hours postmeal) on Day 2 in each treatment period.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

6 hours postdose (4 hours postmeal) on Day 2

Results posted on

2017-05-15

Participant Flow

Participant milestones

Participant milestones
Measure	All Participants Participants received four 2-day treatment regimens (sitagliptin + placebo metformin for 2 days, metformin + placebo sitagliptin for 2 days, co-administration of sitagliptin + metformin for 2 days, and placebo sitagliptin + placebo metformin for 2 days) with a 7-day washout between each treatment period.
Sitagliptin + Placebo Metformin STARTED	18
Sitagliptin + Placebo Metformin COMPLETED	18
Sitagliptin + Placebo Metformin NOT COMPLETED	0
7-day Washout STARTED	18
7-day Washout COMPLETED	18
7-day Washout NOT COMPLETED	0
Metformin + Placebo Sitagliptin STARTED	18
Metformin + Placebo Sitagliptin COMPLETED	18
Metformin + Placebo Sitagliptin NOT COMPLETED	0
Sitagliptin + Metformin STARTED	18
Sitagliptin + Metformin COMPLETED	18
Sitagliptin + Metformin NOT COMPLETED	0
Placebo Sitagliptin + Placebo Metformin STARTED	18
Placebo Sitagliptin + Placebo Metformin COMPLETED	18
Placebo Sitagliptin + Placebo Metformin NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of the Effects of Co-Administration of Sitagliptin (MK-0431) and Metformin on Incretin Hormone Concentrations (MK-0431-110)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=18 Participants Participants received four 2-day treatment regimens (sitagliptin + placebo metformin for 2 days, metformin + placebo sitagliptin for 2 days, co-administration of sitagliptin + metformin for 2 days, and placebo sitagliptin + placebo metformin for 2 days) with a 7-day washout between each treatment period.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 hours postdose (4 hours postmeal) on Day 2

Meal was given 2 hours postdose. Blood samples for determination of active GLP-1 concentration were collected (4 hours postmeal) on Day 2 in each treatment period.

Outcome measures

Outcome measures
Measure	All Participants n=18 Participants Participants received four 2-day treatment regimens (sitagliptin + placebo metformin for 2 days, metformin + placebo sitagliptin for 2 days, co-administration of sitagliptin + metformin for 2 days, and placebo sitagliptin + placebo metformin for 2 days) with a 7-day washout between each treatment period.
Incremental Post-prandial 4-hour Weighted Mean Active Glucagon-like Peptide-1 (GLP-1) Plasma Concentrations Sitagliptin + placebo metformin	6.00 picomolar Interval 4.53 to 7.94
Incremental Post-prandial 4-hour Weighted Mean Active Glucagon-like Peptide-1 (GLP-1) Plasma Concentrations Metformin + placebo sitagliptin	4.09 picomolar Interval 3.09 to 5.42
Incremental Post-prandial 4-hour Weighted Mean Active Glucagon-like Peptide-1 (GLP-1) Plasma Concentrations Sitagliptin + metformin	7.22 picomolar Interval 5.45 to 9.55
Incremental Post-prandial 4-hour Weighted Mean Active Glucagon-like Peptide-1 (GLP-1) Plasma Concentrations Placebo sitagliptin + placebo metformin	1.55 picomolar Interval 1.17 to 2.05

SECONDARY outcome

Timeframe: 6 hour post-dose (4 hour postmeal) on Day 2

Population: Beta-cell sensitivity was not calculated for 1 participant following the administration of sitagliptin alone and metformin alone due to missing insulin data.

β-cell sensitivity was defined as the incremental post-prandial 4-hour area under the curve (AUC) for insulin secretion rate (ISR) normalized by the incremental post-prandial 4-hour plasma glucose AUC.

Outcome measures

Outcome measures
Measure	All Participants n=18 Participants Participants received four 2-day treatment regimens (sitagliptin + placebo metformin for 2 days, metformin + placebo sitagliptin for 2 days, co-administration of sitagliptin + metformin for 2 days, and placebo sitagliptin + placebo metformin for 2 days) with a 7-day washout between each treatment period.
β-cell Sensitivity Sitagliptin + placebo metformin, n=17	19.50 (ng/min)/(mg/dL)*10^ -3 Interval 11.89 to 32.0
β-cell Sensitivity Metformin + placebo sitagliptin, n=17	25.71 (ng/min)/(mg/dL)*10^ -3 Interval 15.67 to 42.18
β-cell Sensitivity Sitagliptin + metformin, n=18	26.39 (ng/min)/(mg/dL)*10^ -3 Interval 16.18 to 43.05
β-cell Sensitivity Placebo sitagliptin + placebo metformin, n=18	15.44 (ng/min)/(mg/dL)*10^ -3 Interval 9.46 to 25.19

SECONDARY outcome

Timeframe: 6 hours postdose (4 hours postmeal) on Day 2

Meal was given 2 hours postdose. Blood samples for determination of glucose concentration were collected (4 hours postmeal) on Day 2 in each treatment period.

Outcome measures

Outcome measures
Measure	All Participants n=18 Participants Participants received four 2-day treatment regimens (sitagliptin + placebo metformin for 2 days, metformin + placebo sitagliptin for 2 days, co-administration of sitagliptin + metformin for 2 days, and placebo sitagliptin + placebo metformin for 2 days) with a 7-day washout between each treatment period.
Incremental Post-prandial 4-hour Weighted Mean Plasma Glucose Concentrations Sitagliptin + placebo metformin	42.30 mg/dL Interval 30.51 to 54.08
Incremental Post-prandial 4-hour Weighted Mean Plasma Glucose Concentrations Metformin + placebo sitagliptin	29.33 mg/dL Interval 17.55 to 41.12
Incremental Post-prandial 4-hour Weighted Mean Plasma Glucose Concentrations Sitagliptin + metformin	20.02 mg/dL Interval 8.24 to 31.81
Incremental Post-prandial 4-hour Weighted Mean Plasma Glucose Concentrations Placebo sitagliptin + placebo metformin	51.02 mg/dL Interval 39.24 to 62.81

Adverse Events

Sitagliptin + Placebo Metformin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Metformin + Placebo Sitagliptin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Sitagliptin + Metformin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo Sitagliptin + Placebo Metformin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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

Measure	Sitagliptin + Placebo Metformin n=18 participants at risk Participants received sitagliptin + placebo metformin for 2 days.	Metformin + Placebo Sitagliptin n=18 participants at risk Participants received metformin + placebo sitagliptin for 2 days.	Sitagliptin + Metformin n=18 participants at risk Participants received co-administration of sitagliptin + metformin for 2 days.	Placebo Sitagliptin + Placebo Metformin n=18 participants at risk Participants received placebo sitagliptin + placebo metformin for 2 days.
Blood and lymphatic system disorders Iron Deficiency anaemia	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Eye disorders Conjunctival haemorrhage	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Eye disorders Vision blurred	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Gastrointestinal disorders Diarrhoea	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Gastrointestinal disorders Dyspepsia	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Gastrointestinal disorders Nausea	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Gastrointestinal disorders Vomiting	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
General disorders Fatigue	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
General disorders Vessel puncture site pain	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Infections and infestations Subcutaneous abscess	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Investigations Hepatic enzyme increased	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Nervous system disorders Headache	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	11.1% 2/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Psychiatric disorders Anxiety	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.6% 1/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)	0.00% 0/18 • 43 days (four 2-day treatment periods, a 7-day washout interval between each treatment period, and approximately 14 days following the last dose of study treatment)