Trial Outcomes & Findings for Double-blind Sitagliptin Add-on Study in Japanese Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Ipragliflozin (MK-0431J-842) (NCT NCT02577016)

Results Overview

HbA1c is measured as percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent. Statistical analysis based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, and treatment by time by prior use of AHAs with the constraint that the mean baseline is the same for both treatment groups.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

141 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2018-08-31

Participant Flow

Prior to randomization, all participants received placebo for 2 weeks.

Participant milestones

Participant milestones
Measure	Sitagliptin + Ipragliflozin Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Overall Study STARTED	70	71
Overall Study COMPLETED	68	69
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin + Ipragliflozin Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Overall Study Adverse Event	2	1
Overall Study Physician Decision	0	1

Baseline Characteristics

All randomized participants with baseline 2-hr PMG measurement.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin + Ipragliflozin n=70 Participants Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin n=71 Participants Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Total n=141 Participants Total of all reporting groups
Age, Continuous	57.0 Years STANDARD_DEVIATION 11.6 • n=70 Participants	54.0 Years STANDARD_DEVIATION 9.5 • n=71 Participants	55.5 Years STANDARD_DEVIATION 10.7 • n=141 Participants
Sex: Female, Male Female	16 Participants n=70 Participants	26 Participants n=71 Participants	42 Participants n=141 Participants
Sex: Female, Male Male	54 Participants n=70 Participants	45 Participants n=71 Participants	99 Participants n=141 Participants
Hemoglobin A1c (HbA1c)	8.01 Percent STANDARD_DEVIATION 0.81 • n=70 Participants	8.08 Percent STANDARD_DEVIATION 0.79 • n=71 Participants	8.04 Percent STANDARD_DEVIATION 0.80 • n=141 Participants
2-hour postmeal glucose (2-hr PMG)	211.9 mg/dL STANDARD_DEVIATION 49.8 • n=70 Participants • All randomized participants with baseline 2-hr PMG measurement.	215.3 mg/dL STANDARD_DEVIATION 47.0 • n=70 Participants • All randomized participants with baseline 2-hr PMG measurement.	213.6 mg/dL STANDARD_DEVIATION 48.3 • n=140 Participants • All randomized participants with baseline 2-hr PMG measurement.
Glucose total AUC0-2hr after meal	414.4 mg･hr/dL STANDARD_DEVIATION 73.8 • n=70 Participants • All randomized participants with baseline Glucose total AUC0-2hr after meal measurement.	422.5 mg･hr/dL STANDARD_DEVIATION 68.2 • n=70 Participants • All randomized participants with baseline Glucose total AUC0-2hr after meal measurement.	418.5 mg･hr/dL STANDARD_DEVIATION 70.9 • n=140 Participants • All randomized participants with baseline Glucose total AUC0-2hr after meal measurement.
Fasting plasma glucose (FPG)	148.8 md/dL STANDARD_DEVIATION 25.4 • n=70 Participants	151.2 md/dL STANDARD_DEVIATION 27.0 • n=71 Participants	150.0 md/dL STANDARD_DEVIATION 26.1 • n=141 Participants
Prior use of other antihyperglycemic agents (AHAs) Yes	24 Participants n=70 Participants	25 Participants n=71 Participants	49 Participants n=141 Participants
Prior use of other antihyperglycemic agents (AHAs) No	46 Participants n=70 Participants	46 Participants n=71 Participants	92 Participants n=141 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of treatment period study medication and have at least one measurement of HbA1c (baseline or post-baseline).

HbA1c is measured as percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent. Statistical analysis based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, and treatment by time by prior use of AHAs with the constraint that the mean baseline is the same for both treatment groups.

Outcome measures

Outcome measures
Measure	Sitagliptin + Ipragliflozin n=70 Participants Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin n=71 Participants Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Change From Baseline in HbA1c at Week 24	-0.69 Percent Interval -0.85 to -0.53	0.14 Percent Interval -0.02 to 0.29

PRIMARY outcome

Timeframe: Up to 26 weeks

Population: All randomized participants who received at least one dose of study medication.

An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Sitagliptin + Ipragliflozin n=70 Participants Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin n=71 Participants Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Percentage of Participants Who Experienced at Least One Adverse Event (AE)	54.3 Percentage of participants	63.4 Percentage of participants

PRIMARY outcome

Timeframe: Up to 24 weeks

Population: All randomized participants who received at least one dose of study medication.

An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Sitagliptin + Ipragliflozin n=70 Participants Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin n=71 Participants Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Percentage of Participants Who Discontinued Study Drug Due to an AE	2.9 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of treatment period study medication and have at least one measurement of 2-hr PMG (baseline or post-baseline).

Change from baseline in 2-hr PMG at Week 24 is defined as Week 24 2-hr PMG minus Week 0 2-hr PMG. Statistical analysis based on a cLDA model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, and treatment by time by prior use of AHAs with the constraint that the mean baseline 2-hr PMG is the same for both treatment groups.

Outcome measures

Outcome measures
Measure	Sitagliptin + Ipragliflozin n=70 Participants Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin n=71 Participants Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Change From Baseline in 2-hr PMG at Week 24	-39.0 mg/dL Interval -48.1 to -29.9	3.4 mg/dL Interval -5.5 to 12.3

SECONDARY outcome

Timeframe: Baseline and Week 24 (just before loading meal [0 min], 30 min, 60 min and 120 min)

Population: All randomized participants who received at least one dose of treatment period study medication and have at least one measurement of glucose total AUC0-2hr after meal (baseline or post-baseline).

Change from Baseline in Glucose Total AUC0-2hr after Meal at Week 24 is defined as Week 24 Glucose Total AUC0-2hr after a meal minus Week 0 Glucose Total AUC0-2hr after a meal. Statistical analysis based on a cLDA model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, and treatment by time by prior use of AHAs with the constraint that the mean baseline glucose total AUC0-2hr after meal is the same for both treatment groups.

Outcome measures

Outcome measures
Measure	Sitagliptin + Ipragliflozin n=70 Participants Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin n=71 Participants Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Change From Baseline in Glucose Total Area Under the Plasma Concentration Curve From Hour 0 to Hour 2 (AUC0-2hr) After Meal at Week 24	-65.7 mg･hr/dL Interval -79.2 to -52.2	1.3 mg･hr/dL Interval -11.9 to 14.5

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: All randomized participants who received at least one dose of treatment period study medication and have at least one measurement of FPG (baseline or post-baseline).

Change from baseline in FPG at Week 24 is defined as Week 24 FPG minus Week 0 FPG. Statistical analysis based on a cLDA model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, and treatment by time by prior use of AHAs with the constraint that the mean baseline FPG is the same for both treatment groups.

Outcome measures

Outcome measures
Measure	Sitagliptin + Ipragliflozin n=70 Participants Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin n=71 Participants Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Change From Baseline in FPG at Week 24	-11.8 mg/dL Interval -16.3 to -7.4	-0.6 mg/dL Interval -5.0 to 3.8

Adverse Events

Sitagliptin + Ipragliflozin

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo + Ipragliflozin

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sitagliptin + Ipragliflozin n=70 participants at risk Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin n=71 participants at risk Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Gastrointestinal disorders Enteritis	1.4% 1/70 • Number of events 1 • Up to 26 weeks	0.00% 0/71 • Up to 26 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	1.4% 1/70 • Number of events 1 • Up to 26 weeks	0.00% 0/71 • Up to 26 weeks
Psychiatric disorders Suicide attempt	1.4% 1/70 • Number of events 1 • Up to 26 weeks	0.00% 0/71 • Up to 26 weeks

Other adverse events

Other adverse events
Measure	Sitagliptin + Ipragliflozin n=70 participants at risk Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.	Placebo + Ipragliflozin n=71 participants at risk Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Infections and infestations Nasopharyngitis	8.6% 6/70 • Number of events 7 • Up to 26 weeks	25.4% 18/71 • Number of events 24 • Up to 26 weeks
Skin and subcutaneous tissue disorders Eczema	5.7% 4/70 • Number of events 4 • Up to 26 weeks	0.00% 0/71 • Up to 26 weeks

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 trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Publication restrictions are in place

Restriction type: OTHER