Trial Outcomes & Findings for Sitagliptin/Metformin (JANUMET) Re-examination Study (0431A-182) (NCT NCT01065766)

Last Updated: 2015-03-06

Results Overview

An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.

Recruitment status

COMPLETED

Target enrollment

4065 participants

Primary outcome timeframe

Up to 26 weeks

Results posted on

2015-03-06

Participant Flow

In this post-marketing surveillance study of sitagliptin/metformin (JANUMET®), participants in South Korea treated for \>= 24 weeks were evaluated for long-term safety and efficacy. During the re-examination study period (December 4, 2005 to September 20, 2013), case report forms (CRFs) were collected from 4,065 participants.

Participant milestones

Participant milestones
Measure	All Participants Included in the Safety Evaluation Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Overall Study STARTED	4065
Overall Study COMPLETED	4033
Overall Study NOT COMPLETED	32

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants Included in the Safety Evaluation Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Overall Study Assessed before the contracted date	1
Overall Study Contraindication to administration	6
Overall Study Violated dosage/administration	25

Baseline Characteristics

Sitagliptin/Metformin (JANUMET) Re-examination Study (0431A-182)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants Included in the Safety Evaluation n=4033 Participants Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Age, Continuous	58.22 Years STANDARD_DEVIATION 11.55 • n=5 Participants
Sex: Female, Male Female	1913 Participants n=5 Participants
Sex: Female, Male Male	2120 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 26 weeks

Population: All participants who were included in the safety evaluation

Outcome measures

Outcome measures
Measure	All Participants Included in the Safety Evaluation n=4033 Participants Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Percentage of Participants With Any Adverse Experience	3.74 Percentage of participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: All participants with a pre-treatment and a 12-week post-treatment HbA1c value.

HbA1C is found when high blood levels of glucose combines with hemoglobin to form glycated hemoglobin. The average amount of glucose in blood over a prolonged periods of time can be determined by measuring a hemoglobin A1c level which is reported as a percentage (%). The change from baseline reflects the Week 12 A1C minus Week 0 A1C.

Outcome measures

Outcome measures
Measure	All Participants Included in the Safety Evaluation n=1597 Participants Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Change From Baseline to Treatment in Hemoglobin HbA1c (A1C) at Week 12	-0.93 Percentage of glycosylated hemoglobin Standard Deviation 1.23

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Participants with a pre-treatment and a 12-week post-treatment measurement of FPG.

Blood glucose was measured on a fasting basis (collected after an 8- to 10-hour fast). FPG is expressed as mg/dL. Therefore, this change from baseline reflects the Week 12 FPG minus Week 0 FPG.

Outcome measures

Outcome measures
Measure	All Participants Included in the Safety Evaluation n=1343 Participants Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Change From Baseline to Treatment in Fasting Plasma Glucose (FPG) at Week 12	-28.21 mg/dL Standard Deviation 42.21

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Participants with a pre-treatment and a 12-week post-treatment measurement of 2hr-PPG.

Blood glucose was measured 2 hours after a meal (2hr-PPG). 2hr-PPG is expressed as mg/dL. Therefore, this change from baseline reflects the Week 12 2hr-PPG minus Week 0 2hr-PPG.

Outcome measures

Outcome measures
Measure	All Participants Included in the Safety Evaluation n=1219 Participants Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Change From Baseline in 2-hour Post Prandial Glucose (2hr-PPG) at Week 12	-58.02 mg/dL Standard Deviation 72.96

PRIMARY outcome

Timeframe: At Week 12

Population: Participants who have used study drug for more than 12 weeks and whose improvement of the disease has been assessed by Principal investigator.

Overall efficacy analysis was conducted on participants who have used study drug for more than 12 weeks and whose improvement of the disease has been assessed by Principal investigator. The investigator's global assessment of disease improvement was classified as either: "Improved", "Stable" and "Worse" in a Medical History/Physical Examination form.

Outcome measures

Outcome measures
Measure	All Participants Included in the Safety Evaluation n=3241 Participants Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Percentage of Participants With an Overall Efficacy Evaluation by the Investigator of Improved, Stable, or Worse at Week 12 Improved	78.68 Percentage of participants
Percentage of Participants With an Overall Efficacy Evaluation by the Investigator of Improved, Stable, or Worse at Week 12 Stable	16.38 Percentage of participants
Percentage of Participants With an Overall Efficacy Evaluation by the Investigator of Improved, Stable, or Worse at Week 12 Worse	4.94 Percentage of participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: All participants with a pre-treatment and a 24-week post-treatment HbA1c value.

HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Therefore, this change from baseline reflects the Week 24 A1C minus Week 0 A1C.

Outcome measures

Outcome measures
Measure	All Participants Included in the Safety Evaluation n=347 Participants Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Change From Baseline to Treatment in HbA1c at Week 24	-1.08 Percentage of glycosylated hemoglobin Standard Deviation 1.42

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Participants with a pre-treatment and a 24-week post-treatment measurement of FPG.

Blood glucose was measured on a fasting basis (collected after an 8- to 10-hour fast). FPG is expressed as mg/dL. Therefore, this change from baseline reflects the Week 24 FPG minus Week 0 FPG.

Outcome measures

Outcome measures
Measure	All Participants Included in the Safety Evaluation n=230 Participants Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Change From Baseline to Treatment in FPG at Week 24	-32.40 mg/dL Standard Deviation 44.75

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Participants with a pre-treatment and a 24-week post-treatment measurement of 2hr-PPG.

Blood glucose was measured 2 hours after a meal (2hr-PPG). 2hr-PPG is expressed as mg/dL. Therefore, this change from baseline reflects the Week 24 2hr-PPG minus Week 0 2hr-PPG.

Outcome measures

Outcome measures
Measure	All Participants Included in the Safety Evaluation n=218 Participants Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Change From Baseline in 2hr-PPG at Week 24	-62.13 mg/dL Standard Deviation 75.67

PRIMARY outcome

Timeframe: At Week 24

Population: Participants who have used study drug for more than 24 weeks and whose improvement of the disease has been assessed by Principal investigator.

Overall efficacy analysis was conducted on participants who have used study drug for more than 24 weeks and whose improvement of the disease has been assessed by Principal investigator. The investigator's global assessment of disease improvement was classified as either: "Improved", "Stable" and "Worse" in a Medical History/Physical Examination form.

Outcome measures

Outcome measures
Measure	All Participants Included in the Safety Evaluation n=800 Participants Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Percentage of Participants With an Overall Efficacy Evaluation by the Investigator of Improved, Stable, or Worse at Week 24 Improved	76.38 Percentage of participants
Percentage of Participants With an Overall Efficacy Evaluation by the Investigator of Improved, Stable, or Worse at Week 24 Stable	15.88 Percentage of participants
Percentage of Participants With an Overall Efficacy Evaluation by the Investigator of Improved, Stable, or Worse at Week 24 Worse	7.75 Percentage of participants

Adverse Events

All Participants Included in the Safety Evaluation

Serious events: 17 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Participants Included in the Safety Evaluation n=4033 participants at risk Korean participants with type 2 diabetes mellitus treated with sitagliptin/metformin
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Cardiac disorders ANGINA UNSTABLE	0.05% 2/4033 • Number of events 2 • Up to 26 weeks
Cardiac disorders ATRIAL FLUTTER	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Cardiac disorders CORONARY ARTERY OCCLUSION	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Gastrointestinal disorders ABDOMINAL PAIN	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Gastrointestinal disorders INGUINAL HERNIA	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Gastrointestinal disorders OESOPHAGEAL VARICES HAEMORRHAGE	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Gastrointestinal disorders VOMITING	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
General disorders CHEST PAIN	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Hepatobiliary disorders BILE DUCT STONE	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Infections and infestations CHRONIC HEPATITIS C	0.02% 1/4033 • Number of events 2 • Up to 26 weeks
Metabolism and nutrition disorders HYPERLIPIDAEMIA	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) THYROID NEOPLASM	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Nervous system disorders DIZZINESS	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Nervous system disorders HEADACHE	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Nervous system disorders TENSION HEADACHE	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Renal and urinary disorders RENAL FAILURE ACUTE	0.02% 1/4033 • Number of events 1 • Up to 26 weeks
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.05% 2/4033 • Number of events 2 • Up to 26 weeks
Surgical and medical procedures KNEE ARTHROPLASTY	0.02% 1/4033 • Number of events 1 • Up to 26 weeks

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-888-577-8839

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In regard to surveillance result, any publication should be agreed by sponsor in advance.
Publication restrictions are in place

Restriction type: OTHER