Trial Outcomes & Findings for Effect of SCH 497079 on Metabolic Parameters and Influence of Race/Ethnic Origin on Therapeutic Response (Study P05338)(COMPLETED) (NCT NCT00673465)

Last Updated: 2018-09-10

Results Overview

Change from baseline in 24-hour plasma glucose on the last day of treatment. On the day of the glucose collections (and the day prior to), standardized meals breakfast, lunch, dinner, and snack) were provided and consumed over 15 minutes. AUC/duration is presented as mg/dL and was calculated by dividing AUC (mg/dL\*hr) by the duration in hours. Model-based least squares mean: ANOVA extracting the effects due to treatment, sequence, period and participant.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

17 participants

Primary outcome timeframe

Pre-dose (-30 minutes), pre-standard breakfast (0 hour), 0.5, .75, 1, 2, 3, 4, 4.5, 4.75, 5, 6, 7, 8, 9, 9.5, 9.75, 10, 11, 12, 13, 14, 15, 16, and 24 hours after the beginning of the standardized breakfast on Day -1 and Day 28

Results posted on

2018-09-10

Participant Flow

Part 1 was conducted in the United States. If an analysis at the end of Part 1 demonstrated that SCH 497079 exhibited a clinically significant glucose lowering effect, Part 2 was to be conducted in India. Part 2 of the study was not conducted.

Participant milestones

Participant milestones
Measure	Part 1/Treatment Sequence 1: SCH 497079 → Placebo → Metformin Participants received SCH 497079 daily for 4 weeks (Period 1) followed by placebo daily for 4 weeks (Period 2) followed by metformin daily for 4 weeks (Period 3).	Part 1/Treatment Sequence 2: Placebo → Metformin → SCH 497079 Participants received placebo daily for 4 weeks (Period 1) followed by metformin daily for 4 weeks (Period 2)followed by SCH 497079 daily for 4 weeks (Period 3).	Part 1/Treatment Sequence 3: Metformin → SCH 497079 → Placebo Participants received metformin daily for 4 weeks (Period 1) followed by SCH 497079 daily for 4 weeks (Period 2)followed by placebo daily for 4 weeks (Period 3).	Part 1/Treatment Sequence 4: SCH 497079 → Metformin → Placebo Participants received SCH 497079 daily for 4 weeks (Period 1) followed by metformin daily for 4 weeks (Period 2) followed by placebo daily for 4 weeks (Period 3).	Part 1/Treatment Sequence 5: Placebo → SCH 49709 → Metformin Participants received placebo daily for 4 weeks (Period 1) followed by SCH 497079 daily for 4 weeks (Period 2) followed by metformin daily for 4 weeks (Period 3).	Part 1/Treatment Sequence 6: Metformin → Placebo → SCH 497079 Participants received metformin daily for 4 weeks (Period 1) followed by placebo daily for 4 weeks (Period 2) followed by SCH 497079 daily for 4 weeks (Period 3).
Part 1/Period 1 (United States) STARTED	3	3	3	3	3	2
Part 1/Period 1 (United States) COMPLETED	3	3	3	3	2	1
Part 1/Period 1 (United States) NOT COMPLETED	0	0	0	0	1	1
Part 1/Period 2 (United States) STARTED	3	3	3	3	2	1
Part 1/Period 2 (United States) COMPLETED	3	3	3	3	1	1
Part 1/Period 2 (United States) NOT COMPLETED	0	0	0	0	1	0
Part 1/Period 3 (United States) STARTED	3	3	3	3	1	1
Part 1/Period 3 (United States) COMPLETED	3	3	3	3	1	1
Part 1/Period 3 (United States) NOT COMPLETED	0	0	0	0	0	0
Part 2 (India) STARTED	0	0	0	0	0	0
Part 2 (India) COMPLETED	0	0	0	0	0	0
Part 2 (India) NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1/Treatment Sequence 1: SCH 497079 → Placebo → Metformin Participants received SCH 497079 daily for 4 weeks (Period 1) followed by placebo daily for 4 weeks (Period 2) followed by metformin daily for 4 weeks (Period 3).	Part 1/Treatment Sequence 2: Placebo → Metformin → SCH 497079 Participants received placebo daily for 4 weeks (Period 1) followed by metformin daily for 4 weeks (Period 2)followed by SCH 497079 daily for 4 weeks (Period 3).	Part 1/Treatment Sequence 3: Metformin → SCH 497079 → Placebo Participants received metformin daily for 4 weeks (Period 1) followed by SCH 497079 daily for 4 weeks (Period 2)followed by placebo daily for 4 weeks (Period 3).	Part 1/Treatment Sequence 4: SCH 497079 → Metformin → Placebo Participants received SCH 497079 daily for 4 weeks (Period 1) followed by metformin daily for 4 weeks (Period 2) followed by placebo daily for 4 weeks (Period 3).	Part 1/Treatment Sequence 5: Placebo → SCH 49709 → Metformin Participants received placebo daily for 4 weeks (Period 1) followed by SCH 497079 daily for 4 weeks (Period 2) followed by metformin daily for 4 weeks (Period 3).	Part 1/Treatment Sequence 6: Metformin → Placebo → SCH 497079 Participants received metformin daily for 4 weeks (Period 1) followed by placebo daily for 4 weeks (Period 2) followed by SCH 497079 daily for 4 weeks (Period 3).	Part 2/Treatment Sequence 1: SCH 497079 → Placebo → Metformin Participants received SCH 497079 daily for 4 weeks (Period 1) followed by placebo daily for 4 weeks (Period 2) followed by metformin daily for 4 weeks (Period 3).	Part 2/Treatment Sequence 2: Placebo → Metformin → SCH 497079 Participants received placebo daily for 4 weeks (Period 1) followed by metformin daily for 4 weeks (Period 2) followed by SCH 497079 daily for 4 weeks (Period 3).	Part 2/Treatment Sequence 3: Metformin → SCH 497079 → Placebo Participants received metformin daily for 4 weeks (Period 1) followed by SCH 497079 daily for 4 weeks (Period 2) followed by placebo daily for 4 weeks (Period 3).	Part 2/Treatment Sequence 4: SCH 497079 → Metformin → Placebo Participants received SCH 497079 daily for 4 weeks (Period 1) followed by metformin daily for 4 weeks (Period 2) followed by placebo daily for 4 weeks (Period 3).	Part 2/Treatment Sequence 5: Placebo → SCH 49709 → Metformin Participants received placebo daily for 4 weeks (Period 1) followed by SCH 497079 daily for 4 weeks (Period 2) followed by metformin daily for 4 weeks (Period 3).	Part 2/Treatment Sequence 6: Metformin → Placebo → SCH 497079 Participants received metformin daily for 4 weeks (Period 1) followed by placebo daily for 4 weeks(Period 2) followed by SCH 497079 daily for 4 weeks (Period 3).
Part 1/Period 1 (United States) Protocol Violation	0	0	0	0	1	1	0	0	0	0	0	0
Part 1/Period 2 (United States) Protocol Violation	0	0	0	0	1	0	0	0	0	0	0	0

Baseline Characteristics

Effect of SCH 497079 on Metabolic Parameters and Influence of Race/Ethnic Origin on Therapeutic Response (Study P05338)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Treated Participants n=17 Participants All participants received SCH 497079 for 4 weeks, placebo for 4 weeks, and metformin for 4 weeks during one of three parts of the study.
Age, Continuous	54.1 Years STANDARD_DEVIATION 8.1 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
24-hour plasma glucose (AUC/duration)	207 mg/dL STANDARD_DEVIATION 34 • n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose (-30 minutes), pre-standard breakfast (0 hour), 0.5, .75, 1, 2, 3, 4, 4.5, 4.75, 5, 6, 7, 8, 9, 9.5, 9.75, 10, 11, 12, 13, 14, 15, 16, and 24 hours after the beginning of the standardized breakfast on Day -1 and Day 28

Population: All participants who completed study treatment with at least SCH 497079 and placebo.

Outcome measures

Outcome measures
Measure	SCH 497079 n=14 Participants Participants received SCH 497079 daily for 4 weeks during one period of the study.	Placebo n=15 Participants Participants received placebo daily for 4 weeks during one period of the study.	Metformin n=14 Participants Participants received metformin daily for 4 weeks during one period of the study.
Pharmacodynamic: Change From Baseline in Mean 24-hour Plasma Glucose (AUC/Duration) at Week 4 (Part 1 - United States)	-4.27 mg/dL Standard Error 7.35	0.13 mg/dL Standard Error 7.09	-53.8 mg/dL Standard Error 7.32

PRIMARY outcome

Timeframe: Pre-dose (-30 mnutes), pre-standard breakfast (0 hour), 0.5, .75, 1, 2, 3, 4, 4.5, 4.75, 5, 6, 7, 8, 9, 9.5, 9.75, 10, 11, 12, 13, 14, 15, 16, and 24 hours after the beginning of the standardized breakfast on Day -1 and Day 28

Population: No participants were randomized to treatment during Part 2 of the study.

Change from baseline in 24-hour plasma glucose on the last day of treatment. On the day of the glucose collections (and the day prior to), standardized meals (breakfast, lunch, dinner, and snack) were provided and consumed over 15 minutes. AUC/duration is presented as mg/dL and was calculated by dividing AUC (mg/dL\*hr) by the duration in hours. Model-based least squares mean: ANOVA extracting the effects due to treatment, sequence, period and participant.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 14 days after last dose of study drug (up to 98 days)

Population: All randomized participants.

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which does not necessarily have a causal relationship with the treatment. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.

Outcome measures

Outcome measures
Measure	SCH 497079 n=15 Participants Participants received SCH 497079 daily for 4 weeks during one period of the study.	Placebo n=16 Participants Participants received placebo daily for 4 weeks during one period of the study.	Metformin n=15 Participants Participants received metformin daily for 4 weeks during one period of the study.
Number of Participants Who Experienced at Least One Adverse Event (Part 1 - United States)	9 Participants	6 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to 14 days after last dose of study drug (up to 98 days)

Population: No participants were randomized to treatment during Part 2 of the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: All participants who completed study treatment with at least SCH 497079 and placebo.

The postprandial period is defined as the sum of 4 hours after breakfast, 4 hours after lunch and 4 hours after dinner for a total of 12 hours. AUC/duration is presented as mg/dL and was calculated by dividing AUC (mg/dL\*hr) by the duration in hours. Model-based least squares mean: ANOVA extracting the effects due to treatment, sequence, period and participant.

Outcome measures

Outcome measures
Measure	SCH 497079 n=14 Participants Participants received SCH 497079 daily for 4 weeks during one period of the study.	Placebo n=15 Participants Participants received placebo daily for 4 weeks during one period of the study.	Metformin n=14 Participants Participants received metformin daily for 4 weeks during one period of the study.
Pharmacodynamic: Change From Baseline in 12-hour Postprandial Plasma Glucose (AUC/Duration) at Week 4 (Part 1 - United States)	0.42 mg/dL Standard Error 8.67	3.22 mg/dL Standard Error 8.35	-60.3 mg/dL Standard Error 8.64

SECONDARY outcome

Population: No participants were randomized to treatment during Part 2 of the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: All participants who completed study treatment with at least SCH 497079 and placebo.

The post absorptive state is defined as the remaining part of day and night that is not the postprandial period. The postprandial period is defined as the sum of 4 hours after breakfast, 4 hours after lunch and 4 hours after dinner for a total of 12 hours. AUC/duration is presented as mg/dL and was calculated by dividing AUC (mg/dL\*hr) by the duration in hours. Model-based least squares mean: ANOVA extracting the effects due to treatment, sequence, period and participant.

Outcome measures

Outcome measures
Measure	SCH 497079 n=14 Participants Participants received SCH 497079 daily for 4 weeks during one period of the study.	Placebo n=15 Participants Participants received placebo daily for 4 weeks during one period of the study.	Metformin n=14 Participants Participants received metformin daily for 4 weeks during one period of the study.
Pharmacodynamic: Change From Baseline in Plasma Glucose During the 12-hour Post Absorptive State (AUC/Duration) at Week 4 (Part 1 - United States)	-5.37 mg/dL Standard Error 3.85	-1.78 mg/dL Standard Error 3.72	-28.4 mg/dL Standard Error 3.84

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: No participants were randomized to treatment during Part 2 of the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug

Population: No efficacy summary or analysis was completed for this outcome measure since the Part 1 objective was not met (i.e., to determine the 24-hour glycemic profile of type 2 diabetes mellitus \[T2DM\] participants after four weeks of treatment with SCH 497079 vs. placebo).

Blood samples for SCH 497079 pharmacokinetics will be collected at pre-dose/0-hour on Day 1 (Period 1 only) and pre-dose Day 14 and pre-dose/0-hour and at 0.5, 1, 2, 6, 12, and 24 hours post study drug administration (not breakfast) on Day 28 of the placebo and SCH 497079 periods only. In addition to these time points, a sample for metformin level will also be collected pre-dose on Day 1, Day 14, and Day 28 of the metformin administration period only.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug

Population: No participants were randomized to treatment during Part 2 of the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug

Population: No efficacy summary or analysis was completed for this outcome measure since the Part 1 objective was not met (i.e., to determine the 24-hour glycemic profile of T2DM participants after four weeks of treatment with SCH 497079 vs. placebo).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug

Population: No participants were randomized to treatment during Part 2 of the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 6, 12, and 24 hours after administration of study drug

Population: No participants were randomized to treatment during Part 2 of the study.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

SCH 497079

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

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 investigator agrees not to publish or publicly present any interim results of the study without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study.
Publication restrictions are in place

Restriction type: OTHER