Trial Outcomes & Findings for Dose Response Finding Study of MK-0431/ONO-5435 in Japanese Subjects With Impaired Glucose Tolerance (MK-0431-105) (NCT NCT01405911)

Results Overview

An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

242 participants

Primary outcome timeframe

Up to 10 weeks

Results posted on

2020-01-18

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 25 mg Participants received one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 50 mg Participants received one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks.
Overall Study STARTED	83	82	77
Overall Study Treated	82	82	77
Overall Study COMPLETED	79	79	76
Overall Study NOT COMPLETED	4	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 25 mg Participants received one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 50 mg Participants received one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks.
Overall Study Pre-treatment lab AE	0	1	0
Overall Study Lost to Follow-up	0	1	0
Overall Study Protocol Violation	1	0	0
Overall Study Withdrawal by Subject	3	1	1

Baseline Characteristics

Dose Response Finding Study of MK-0431/ONO-5435 in Japanese Subjects With Impaired Glucose Tolerance (MK-0431-105)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=83 Participants Participants received one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 25 mg n=82 Participants Participants received one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 50 mg n=77 Participants Participants received one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks.	Total n=242 Participants Total of all reporting groups
Age, Continuous	61.9 Years STANDARD_DEVIATION 10.6 • n=5 Participants	63.1 Years STANDARD_DEVIATION 9.5 • n=7 Participants	61.9 Years STANDARD_DEVIATION 9.3 • n=5 Participants	62.3 Years STANDARD_DEVIATION 9.8 • n=4 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	38 Participants n=7 Participants	32 Participants n=5 Participants	105 Participants n=4 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	44 Participants n=7 Participants	45 Participants n=5 Participants	137 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 8

Population: All participants, as randomized, who received at least one dose of study treatment and have a baseline measurement or post-randomization measurement for the analysis endpoint subsequent to study treatment.

Glucose total AUC 0-2 hours for MTT was measured at Baseline (Week 0) and at Week 8. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at standard meal loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 8, participants received study drug or placebo 30 minutes prior to consuming a standard meal.

Outcome measures

Outcome measures
Measure	Placebo n=82 Participants Participants received one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 25 mg n=82 Participants Participants received one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 50 mg n=77 Participants Participants received one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks.
Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for Meal Tolerance Test (MTT) at Week 8	-2.42 Percent change Interval -4.48 to -0.31	-9.52 Percent change Interval -11.43 to -7.57	-11.49 Percent change Interval -13.4 to -9.55

PRIMARY outcome

Timeframe: Up to 10 weeks

Population: All randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the actual study treatment they received. Due to a prescription error, one participant who was randomized to the placebo group took sitagliptin 50 mg.

An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 25 mg n=82 Participants Participants received one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 50 mg n=78 Participants Participants received one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks.
Percentage of Participants Who Experienced One or More Adverse Events (AEs)	30.9 Percentage of participants	34.1 Percentage of participants	41.0 Percentage of participants

PRIMARY outcome

Timeframe: Up to 8 weeks

Population: All randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the actual study treatment they received. Due to a prescription error, one participant who was randomized to the placebo group took sitagliptin 50 mg.

An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 25 mg n=82 Participants Participants received one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 50 mg n=78 Participants Participants received one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks.
Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE)	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Week -1) and Week 7

Population: All participants, as randomized, who received at least one dose of study treatment and have a baseline measurement or post-randomization measurement for the analysis endpoint subsequent to study treatment.

Glucose total AUC 0-2 hours for 75 g OGTT was measured at Baseline (Week -1) and at Week 7. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at 75 g glucose loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 7, participants received study drug or placebo 30 minutes prior to loading 75 g glucose solution.

Outcome measures

Outcome measures
Measure	Placebo n=82 Participants Participants received one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 25 mg n=82 Participants Participants received one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 50 mg n=77 Participants Participants received one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks.
Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for 75-gram Oral Glucose Tolerance Test (OGTT) at Week 7	-3.68 Percent change Interval -6.66 to -0.6	-21.38 Percent change Interval -23.81 to -18.87	-20.09 Percent change Interval -22.61 to -17.48

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Sitagliptin 25 mg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Sitagliptin 50 mg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=81 participants at risk Participants received one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 25 mg n=82 participants at risk Participants received one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Sitagliptin 50 mg n=78 participants at risk Participants received one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks.
Infections and infestations Nasopharyngitis	8.6% 7/81 • Number of events 7 • Up to 10 weeks The analysis of safety data was based on all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the actual study treatment they received. Due to a prescription error, one participant who was randomized to the placebo group took sitagliptin 50 mg.	11.0% 9/82 • Number of events 9 • Up to 10 weeks The analysis of safety data was based on all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the actual study treatment they received. Due to a prescription error, one participant who was randomized to the placebo group took sitagliptin 50 mg.	9.0% 7/78 • Number of events 7 • Up to 10 weeks The analysis of safety data was based on all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the actual study treatment they received. Due to a prescription error, one participant who was randomized to the placebo group took sitagliptin 50 mg.
Metabolism and nutrition disorders Hypoglycaemia	8.6% 7/81 • Number of events 7 • Up to 10 weeks The analysis of safety data was based on all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the actual study treatment they received. Due to a prescription error, one participant who was randomized to the placebo group took sitagliptin 50 mg.	6.1% 5/82 • Number of events 9 • Up to 10 weeks The analysis of safety data was based on all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the actual study treatment they received. Due to a prescription error, one participant who was randomized to the placebo group took sitagliptin 50 mg.	5.1% 4/78 • Number of events 5 • Up to 10 weeks The analysis of safety data was based on all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the actual study treatment they received. Due to a prescription error, one participant who was randomized to the placebo group took sitagliptin 50 mg.

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. SPONSOR review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER