Trial Outcomes & Findings for A Study in China Evaluating the Safety and Efficacy of Adding Sitagliptin to Stable Therapy With Sulfonylurea With or Without Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-253) (NCT NCT01590771)

NCT ID: NCT01590771

Last Updated: 2018-08-17

Results Overview

A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 498 participants
• Primary outcome timeframe: Baseline and Week 24
• Results posted on: 2018-08-17

Participant Flow

All participants randomized population.

Participant milestones

Measure	Sitagliptin Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Overall Study STARTED	249	249
Overall Study COMPLETED	230	210
Overall Study NOT COMPLETED	19	39

Reasons for withdrawal

Measure	Sitagliptin Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Overall Study Other Protocol Specified Criteria	5	14
Overall Study Withdrawal by Subject	8	15
Overall Study Protocol Violation	1	2
Overall Study Lost to Follow-up	1	1
Overall Study Lack of Efficacy	1	0
Overall Study Adverse Event	3	7

Baseline Characteristics

A Study in China Evaluating the Safety and Efficacy of Adding Sitagliptin to Stable Therapy With Sulfonylurea With or Without Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-253)

Baseline characteristics by cohort

Measure	Sitagliptin n=249 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=249 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Total n=498 Participants Total of all reporting groups
Age, Continuous	57.5 Years STANDARD_DEVIATION 9.5 • n=5 Participants	56.5 Years STANDARD_DEVIATION 9.3 • n=7 Participants	57.0 Years STANDARD_DEVIATION 9.4 • n=5 Participants
Sex: Female, Male Female	132 Participants n=5 Participants	117 Participants n=7 Participants	249 Participants n=5 Participants
Sex: Female, Male Male	117 Participants n=5 Participants	132 Participants n=7 Participants	249 Participants n=5 Participants
Hemoglobin A1c (A1C)	8.61 Percent of glycosylated hemoglobin (A1C) STANDARD_DEVIATION 1.06 • n=5 Participants	8.48 Percent of glycosylated hemoglobin (A1C) STANDARD_DEVIATION 0.91 • n=7 Participants	8.55 Percent of glycosylated hemoglobin (A1C) STANDARD_DEVIATION 0.99 • n=5 Participants
2-hour post meal glucose (2-hr PMG)	296.5 mg/dL STANDARD_DEVIATION 68.0 • n=5 Participants	290.2 mg/dL STANDARD_DEVIATION 72.4 • n=7 Participants	293.4 mg/dL STANDARD_DEVIATION 70.2 • n=5 Participants
Fasting plasma glucose (FPG)	181.5 mg/dL STANDARD_DEVIATION 40.9 • n=5 Participants	179.8 mg/dL STANDARD_DEVIATION 40.7 • n=7 Participants	180.6 mg/dL STANDARD_DEVIATION 40.8 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set consists of all participants who received at least one dose of study drug, have a baseline measurement, and have at least one post-randomization measurement.

A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.

Outcome measures

Measure	Sitagliptin n=243 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=236 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin	-0.88 Percent of glycosylated hemoglobin (A1C) Interval -0.99 to -0.76	-0.27 Percent of glycosylated hemoglobin (A1C) Interval -0.38 to -0.15

PRIMARY outcome

Timeframe: Up to 26 weeks

Population: All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.

An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions.

Outcome measures

Measure	Sitagliptin n=248 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=249 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Number of Participants Who Experienced an Adverse Event	106 Participants	98 Participants

PRIMARY outcome

Timeframe: Up to 24 weeks

Population: All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.

An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions.

Outcome measures

Measure	Sitagliptin n=248 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=249 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event	3 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set consists of all participants who received at least one dose of study drug, have a baseline measurement, and have at least one post-randomization measurement.

This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0.

Outcome measures

Measure	Sitagliptin n=239 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=231 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin	-40.7 mg/dL Interval -49.4 to -31.9	-7.7 mg/dL Interval -16.6 to 1.2

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set consists of all participants who received at least one dose of study drug, have a baseline measurement, and have at least one post-randomization measurement.

This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.

Outcome measures

Measure	Sitagliptin n=246 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=243 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin	-24.4 mg/dL 95% Confidence Interval -29.1 • Interval -29.1 to -19.8	-7.7 mg/dL Interval -12.3 to -3.0

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set (on metformin) consists of all participants on metformin who received at least one dose of study drug, have a baseline measurement, and have at least one post-randomization measurement.

A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.

Outcome measures

Measure	Sitagliptin n=111 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=112 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin	-0.86 Percent of glycosylated hemoglobin (A1C) Interval -1.01 to -0.71	-0.45 Percent of glycosylated hemoglobin (A1C) Interval -0.6 to -0.3

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set (not on metformin) consists of all participants not on metformin who received at least one dose of study drug, have a baseline measurement, and have at least one post-randomization measurement.

A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.

Outcome measures

Measure	Sitagliptin n=132 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=124 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone	-0.85 Percent of glycosylated hemoglobin (A1C) Interval -1.04 to -0.67	-0.05 Percent of glycosylated hemoglobin (A1C) Interval -0.24 to 0.14

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set (on metformin) consists of all participants on metformin who received at least one dose of study drug, have a baseline measurement, and have at least one post-randomization measurement.

This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0.

Outcome measures

Measure	Sitagliptin n=109 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=111 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and a Sulfonylurea in Combination With Metformin	-33.4 mg/dL Interval -43.4 to -23.5	-6.2 mg/dL Interval -16.1 to 3.7

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set (not on metformin) consists of all participants not on metformin who received at least one dose of study drug, have a baseline measurement, and have at least one post-randomization measurement.

This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0.

Outcome measures

Measure	Sitagliptin n=130 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=120 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone	-49.5 mg/dL Interval -62.9 to -36.2	-11.9 mg/dL Interval -25.8 to 2.0

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set (on metformin) consists of all participants on metformin who received at least one dose of study drug, have a baseline measurement, and have at least one post-randomization measurement.

This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.

Outcome measures

Measure	Sitagliptin n=113 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=114 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin	-22.2 mg/dL Interval -28.4 to -16.0	-5.7 mg/dL Interval -11.9 to 0.5

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set (not on metformin) consists of all participants not on metformin who received at least one dose of study drug, have a baseline measurement, and have at least one post-randomization measurement.

This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.

Outcome measures

Measure	Sitagliptin n=133 Participants Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=129 Participants Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone	-26.3 mg/dL Interval -33.3 to -19.4	-9.3 mg/dL Interval -16.3 to -2.3

Adverse Events

Sitagliptin

Serious events: 7 serious events

Other events: 54 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sitagliptin n=248 participants at risk Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=249 participants at risk Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Cardiac disorders Angina pectoris	0.40% 1/248 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.00% 0/249 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Infections and infestations Erysipelas	0.40% 1/248 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.00% 0/249 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Infections and infestations Lung infection	0.40% 1/248 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.00% 0/249 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Infections and infestations Mastitis	0.00% 0/248 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.40% 1/249 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Infections and infestations Pneumonia	0.00% 0/248 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.40% 1/249 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Investigations Blood glucose increased	0.40% 1/248 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.00% 0/249 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/248 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.40% 1/249 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/248 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.40% 1/249 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/248 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.40% 1/249 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.40% 1/248 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.00% 0/249 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Nervous system disorders Thalamus haemorrhage	0.00% 0/248 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.40% 1/249 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Nervous system disorders Vertebrobasilar insufficiency	0.00% 0/248 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.40% 1/249 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Respiratory, thoracic and mediastinal disorders Asthma	0.40% 1/248 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.00% 0/249 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Vascular disorders Hypertension	0.40% 1/248 • Number of events 1 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	0.00% 0/249 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.

Other adverse events

Measure	Sitagliptin n=248 participants at risk Sitagliptin 100 mg once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.	Placebo n=249 participants at risk Matching placebo once daily for 24 weeks. Participants continued pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Infections and infestations Urinary tract infection	5.6% 14/248 • Number of events 14 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	4.4% 11/249 • Number of events 11 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Metabolism and nutrition disorders Hyperlipidaemia	3.2% 8/248 • Number of events 8 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	6.0% 15/249 • Number of events 15 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.
Metabolism and nutrition disorders Hypoglycaemia	14.1% 35/248 • Number of events 76 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.	6.8% 17/249 • Number of events 28 • Up to 26 weeks (including 14 days following the last dose of study medication). All participants as treated population defined as all randomized participants who received at least one dose of study medication. Participants are included in the treatment group corresponding to the study treatment actually received.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding the 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