Trial Outcomes & Findings for Double-blind Ipragliflozin Add-on Study in Japanese Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Sitagliptin (MK-0431J-843) (NCT NCT02577003)

NCT ID: NCT02577003

Last Updated: 2018-09-04

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, treatment by time by prior use of AHAs, and baseline eGFR value with the constraint that the mean baseline HbA1c is the same for both treatment groups.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 143 participants
• Primary outcome timeframe: Baseline and Week 24
• Results posted on: 2018-09-04

Participant Flow

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

Participant milestones

Measure	Ipragliflozin + Sitagliptin Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Overall Study STARTED	73	70
Overall Study COMPLETED	71	65
Overall Study NOT COMPLETED	2	5

Reasons for withdrawal

Measure	Ipragliflozin + Sitagliptin Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Overall Study Adverse Event	2	4
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Double-blind Ipragliflozin Add-on Study in Japanese Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Sitagliptin (MK-0431J-843)

Baseline characteristics by cohort

Measure	Ipragliflozin + Sitagliptin n=73 Participants Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin n=70 Participants Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Total n=143 Participants Total of all reporting groups
Age, Continuous	61.0 Years STANDARD_DEVIATION 9.1 • n=5 Participants	60.0 Years STANDARD_DEVIATION 10.4 • n=7 Participants	60.5 Years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	53 Participants n=7 Participants	107 Participants n=5 Participants
HbA1c	8.05 Percent STANDARD_DEVIATION 0.83 • n=5 Participants	7.99 Percent STANDARD_DEVIATION 0.62 • n=7 Participants	8.02 Percent STANDARD_DEVIATION 0.73 • n=5 Participants
Estimated Glomerular Filtration Rate (eGFR)	82.0 mL/min/1.73m^2 STANDARD_DEVIATION 13.5 • n=5 Participants	83.4 mL/min/1.73m^2 STANDARD_DEVIATION 16.7 • n=7 Participants	82.7 mL/min/1.73m^2 STANDARD_DEVIATION 15.1 • n=5 Participants
Fasting Plasma Glucose (FPG)	158.0 mg/dL STANDARD_DEVIATION 33.2 • n=5 Participants	163.0 mg/dL STANDARD_DEVIATION 26.2 • n=7 Participants	160.5 mg/dL STANDARD_DEVIATION 30.0 • n=5 Participants
2-hour Post-Meal Glucose (2-hr PMG)	225.3 mg/dL STANDARD_DEVIATION 59.9 • n=5 Participants	231.5 mg/dL STANDARD_DEVIATION 48.9 • n=7 Participants	228.3 mg/dL STANDARD_DEVIATION 54.7 • n=5 Participants
Glucose Total Area Under the Plasma Concentration Curve from Hour 0 to Hour 2 (AUC0-2hr) after Meal	429.4 mg･hr/dL STANDARD_DEVIATION 86.3 • n=5 Participants	443.4 mg･hr/dL STANDARD_DEVIATION 67.0 • n=7 Participants	436.2 mg･hr/dL STANDARD_DEVIATION 77.5 • n=5 Participants
Body Weight	69.8 kg STANDARD_DEVIATION 11.7 • n=5 Participants	70.1 kg STANDARD_DEVIATION 11.1 • n=7 Participants	69.9 kg STANDARD_DEVIATION 11.4 • n=5 Participants
Prior use of other antihyperglycemic agents (AHAs) Yes	31 Participants n=5 Participants	30 Participants n=7 Participants	61 Participants n=5 Participants
Prior use of other antihyperglycemic agents (AHAs) No	42 Participants n=5 Participants	40 Participants n=7 Participants	82 Participants n=5 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, treatment by time by prior use of AHAs, and baseline eGFR value with the constraint that the mean baseline HbA1c is the same for both treatment groups.

Outcome measures

Measure	Ipragliflozin + Sitagliptin n=73 Participants Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin n=70 Participants Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Change From Baseline in HbA1c at Week 24	-0.84 Percent Interval -0.99 to -0.69	-0.07 Percent Interval -0.22 to 0.09

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

Measure	Ipragliflozin + Sitagliptin n=73 Participants Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin n=70 Participants Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Percentage of Participants Who Experienced at Least One Adverse Event (AE)	50.7 Percentage of participants	65.7 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

Measure	Ipragliflozin + Sitagliptin n=73 Participants Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin n=70 Participants Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Percentage of Participants Who Discontinued Study Drug Due to an AE	2.7 Percentage of participants	5.7 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 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, treatment by time by prior use of AHAs, and baseline eGFR value with the constraint that the mean baseline FPG is the same for both treatment groups.

Outcome measures

Measure	Ipragliflozin + Sitagliptin n=73 Participants Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin n=70 Participants Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Change From Baseline in FPG at Week 24	-30.3 mg/dL Interval -35.5 to -25.0	-2.1 mg/dL Interval -7.6 to 3.3

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, treatment by time by prior use of AHAs, and baseline eGFR value with the constraint that the mean baseline 2-hr PMG is the same for both treatment groups.

Outcome measures

Measure	Ipragliflozin + Sitagliptin n=73 Participants Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin n=70 Participants Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Change From Baseline in 2-hr PMG at Week 24	-52.4 mg/dL Interval -61.5 to -43.2	-3.8 mg/dL Interval -13.3 to 5.7

SECONDARY outcome

Timeframe: Baseline and Week 24 (just before the 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, and baseline eGFR value with the constraint that the mean baseline glucose total AUC0-2hr after meal is the same for both treatment groups.

Outcome measures

Measure	Ipragliflozin + Sitagliptin n=73 Participants Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin n=70 Participants Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Change From Baseline in Glucose Total AUC0-2hr After Meal at Week 24	-86.9 mg･hr/dL Interval -101.0 to -72.9	-2.3 mg･hr/dL Interval -17.0 to 12.3

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 body weight after meal (baseline or post-baseline).

Change from baseline in body weight at Week 24 is defined as Week 24 body weight minus Week 0 body weight. 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, and baseline eGFR value with the constraint that the mean baseline body weight is the same for both treatment groups.

Outcome measures

Measure	Ipragliflozin + Sitagliptin n=73 Participants Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin n=70 Participants Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Change From Baseline in Body Weight at Week 24	-2.4 kg Interval -2.9 to -1.9	-0.6 kg Interval -1.1 to -0.1

Adverse Events

Ipragliflozin + Sitagliptin

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo + Sitagliptin

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ipragliflozin + Sitagliptin n=73 participants at risk Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin n=70 participants at risk Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Cardiac disorders Angina pectoris	0.00% 0/73 • Up to 26 weeks	1.4% 1/70 • Number of events 1 • Up to 26 weeks
Cardiac disorders Cardiomyopathy	0.00% 0/73 • Up to 26 weeks	1.4% 1/70 • Number of events 1 • Up to 26 weeks
Nervous system disorders Cerebral infarction	1.4% 1/73 • Number of events 1 • Up to 26 weeks	0.00% 0/70 • Up to 26 weeks
Renal and urinary disorders Ureterolithiasis	0.00% 0/73 • Up to 26 weeks	1.4% 1/70 • Number of events 1 • Up to 26 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary mass	1.4% 1/73 • Number of events 1 • Up to 26 weeks	0.00% 0/70 • Up to 26 weeks
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/73 • Up to 26 weeks	1.4% 1/70 • Number of events 1 • Up to 26 weeks

Other adverse events

Measure	Ipragliflozin + Sitagliptin n=73 participants at risk Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.	Placebo + Sitagliptin n=70 participants at risk Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Gastrointestinal disorders Constipation	2.7% 2/73 • Number of events 3 • Up to 26 weeks	5.7% 4/70 • Number of events 4 • Up to 26 weeks
Infections and infestations Nasopharyngitis	13.7% 10/73 • Number of events 12 • Up to 26 weeks	14.3% 10/70 • Number of events 12 • Up to 26 weeks
Injury, poisoning and procedural complications Contusion	0.00% 0/73 • Up to 26 weeks	5.7% 4/70 • Number of events 4 • Up to 26 weeks

Additional Information

Senior Vice President, Global Clinical Dvelopment

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 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