Trial Outcomes & Findings for A Study in China Evaluating the Safety and Efficacy of Adding Sitagliptin to Stable Therapy With Insulin With or Without Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-254) (NCT NCT01590797)

NCT ID: NCT01590797

Last Updated: 2018-08-17

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 467 participants
• Primary outcome timeframe: Baseline and Week 24
• Results posted on: 2018-08-17

Participant Flow

This study was performed with research participants at 28 study centers in China.

Participant milestones

Measure	Sitagliptin Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Placebo Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Overall Study STARTED	234	233
Overall Study COMPLETED	217	217
Overall Study NOT COMPLETED	17	16

Reasons for withdrawal

Measure	Sitagliptin Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Placebo Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Overall Study Adverse Event	4	3
Overall Study Lack of Efficacy	0	2
Overall Study Lost to Follow-up	0	1
Overall Study Protocol Violation	4	1
Overall Study Withdrawal by Subject	7	5
Overall Study Other Protocol Specified Criteria	2	4

Baseline Characteristics

A Study in China Evaluating the Safety and Efficacy of Adding Sitagliptin to Stable Therapy With Insulin With or Without Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-254)

Baseline characteristics by cohort

Measure	Sitagliptin n=234 Participants Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Placebo n=233 Participants Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Total n=467 Participants Total of all reporting groups
Age, Continuous	58.6 Years STANDARD_DEVIATION 8.4 • n=5 Participants	56.7 Years STANDARD_DEVIATION 9.1 • n=7 Participants	57.6 Years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	104 Participants n=5 Participants	117 Participants n=7 Participants	221 Participants n=5 Participants
Sex: Female, Male Male	130 Participants n=5 Participants	116 Participants n=7 Participants	246 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: The Full Analysis Set (FAS) consisted of all randomized participants receiving insulin alone or in combination with metformin, took at least one dose of study treatment, had at least one observation for the analysis endpoint subsequent to the first dose of study treatment, and had baseline data for the analysis endpoint.

Outcome measures

Measure	Sitagliptin n=223 Participants Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Placebo n=219 Participants Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Change From Baseline in Hemoglobin A1C (HbA1C) Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin	-0.67 A1C % Interval -0.79 to -0.55	-0.32 A1C % Interval -0.44 to -0.2

PRIMARY outcome

Timeframe: Up to Week 26

Population: The All Patients as Treated (APaT) population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.

An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Outcome measures

Measure	Sitagliptin n=234 Participants Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Placebo n=233 Participants Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Number of Participants With One or More Adverse Events	126 Participants	116 Participants

PRIMARY outcome

Timeframe: Up to Week 24

Population: The APaT population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Outcome measures

Measure	Sitagliptin n=234 Participants Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Placebo n=233 Participants Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Number of Participants Discontinuing Study Medication Due to an AE	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: The FAS consisted of all randomized participants receiving insulin in combination with metformin, took at least one dose of study treatment, had at least one observation for the analysis endpoint subsequent to the first dose of study treatment, and had baseline data for the analysis endpoint.

Outcome measures

Measure	Sitagliptin n=109 Participants Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Placebo n=104 Participants Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Change From Baseline in HbA1C Levels at Week 24 in Participants Receiving Insulin in Combination With Metformin	-0.72 A1C % Interval -0.89 to -0.55	-0.34 A1C % Interval -0.51 to -0.17

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: The FAS consisted of all randomized participants receiving insulin alone or in combination with metformin, took at least one dose of study treatment, had at least one observation for the analysis endpoint subsequent to the first dose of study treatment, and had baseline data for the analysis endpoint.

Outcome measures

Measure	Sitagliptin n=209 Participants Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Placebo n=203 Participants Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Change From Baseline in 2-Hour Post Meal Glucose Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin	-47.9 mg/dL Interval -57.0 to -38.8	-21.3 mg/dL Interval -30.3 to -12.3

Adverse Events

Sitagliptin

Serious events: 4 serious events

Other events: 83 other events

Deaths: 0 deaths

Placebo

Serious events: 9 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sitagliptin n=234 participants at risk Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Placebo n=233 participants at risk Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Cardiac disorders Acute myocardial infarction	0.43% 1/234 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.00% 0/233 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Cardiac disorders Angina unstable	0.43% 1/234 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.00% 0/233 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Cardiac disorders Coronary artery disease	0.00% 0/234 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.43% 1/233 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Ear and labyrinth disorders Vertigo	0.43% 1/234 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.00% 0/233 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/234 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.43% 1/233 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Gastrointestinal disorders Gastric polyps	0.00% 0/234 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.43% 1/233 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Infections and infestations Diabetic foot infection	0.00% 0/234 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.43% 1/233 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Infections and infestations Lung infection	0.00% 0/234 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.43% 1/233 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/234 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.43% 1/233 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/234 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.43% 1/233 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/234 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.43% 1/233 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Nervous system disorders Cerebral infarction	0.43% 1/234 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.00% 0/233 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Nervous system disorders Vertebrobasilar insufficiency	0.00% 0/234 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.43% 1/233 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Renal and urinary disorders Diabetic nephropathy	0.43% 1/234 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.00% 0/233 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Renal and urinary disorders Renal failure chronic	0.43% 1/234 • Number of events 1 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	0.00% 0/233 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.

Other adverse events

Measure	Sitagliptin n=234 participants at risk Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.	Placebo n=233 participants at risk Participants treated with placebo to sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.
Investigations Blood glucose increased	6.8% 16/234 • Number of events 40 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	5.6% 13/233 • Number of events 32 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Infections and infestations Upper respiratory tract infection	5.1% 12/234 • Number of events 13 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	4.7% 11/233 • Number of events 13 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.
Metabolism and nutrition disorders Hypoglycaemia	27.8% 65/234 • Number of events 173 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.	22.3% 52/233 • Number of events 150 • Up to Week 26 The APaT population consisted of all randomized patients who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received for the analysis of safety data.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

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 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