Trial Outcomes & Findings for Efficacy and Safety of Sotagliflozin in Young Adult Patients With Type 1 Diabetes Mellitus and Elevated Hemoglobin A1C (NCT NCT02383940)
NCT ID: NCT02383940
Last Updated: 2020-02-12
Results Overview
Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Change was calculated by subtracting baseline value from Week 12 value. Least Square (LS) mean changes from baseline were obtained from mixed model repeated measures (MMRM) model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week-4 A1C (\<=10%, \>10%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline A1C-by-time interaction as a covariate.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
87 participants
Primary outcome timeframe
Baseline, Week 12
Results posted on
2020-02-12
Participant Flow
The study was conducted at 15 sites in United States between 20 April 2015 and 23 September 2016.
147 participants were screened and 87 participants with Type 1 diabetes mellitus who had inadequate glycemic control with insulin therapy alone, were randomized equally into two treatment groups: sotagliflozin 400 milligrams (mg) or placebo.
Participant milestones
| Measure |
Placebo
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
|
Sotagliflozin 400 mg
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
44
|
43
|
|
Overall Study
Treated
|
42
|
43
|
|
Overall Study
COMPLETED
|
35
|
40
|
|
Overall Study
NOT COMPLETED
|
9
|
3
|
Reasons for withdrawal
| Measure |
Placebo
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
|
Sotagliflozin 400 mg
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
2
|
|
Overall Study
Physician Decision
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Randomized but not treated
|
2
|
0
|
|
Overall Study
Other than specified above
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Sotagliflozin in Young Adult Patients With Type 1 Diabetes Mellitus and Elevated Hemoglobin A1C
Baseline characteristics by cohort
| Measure |
Placebo
n=42 Participants
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
|
Sotagliflozin 400 mg
n=43 Participants
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
|
Total
n=85 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Body weight
|
77.27 kilogram (kg)
STANDARD_DEVIATION 14.570 • n=99 Participants
|
83.74 kilogram (kg)
STANDARD_DEVIATION 20.439 • n=107 Participants
|
80.54 kilogram (kg)
STANDARD_DEVIATION 17.975 • n=206 Participants
|
|
Age, Continuous
|
21.7 years
STANDARD_DEVIATION 3.55 • n=99 Participants
|
22.8 years
STANDARD_DEVIATION 4.01 • n=107 Participants
|
22.3 years
STANDARD_DEVIATION 3.81 • n=206 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
45 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=99 Participants
|
21 Participants
n=107 Participants
|
40 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
34 Participants
n=99 Participants
|
41 Participants
n=107 Participants
|
75 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Body Mass Index (BMI)
|
26.73 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.993 • n=99 Participants
|
29.39 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 7.214 • n=107 Participants
|
28.07 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 6.324 • n=206 Participants
|
|
Duration of diabetes
|
11.9 years
STANDARD_DEVIATION 5.38 • n=99 Participants
|
11.9 years
STANDARD_DEVIATION 6.16 • n=107 Participants
|
11.9 years
STANDARD_DEVIATION 5.75 • n=206 Participants
|
|
Insulin Delivery Method
Continuous Subcutaneous Insulin Infusion (CSII)
|
23 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
46 Participants
n=206 Participants
|
|
Insulin Delivery Method
Multiple Daily Injections (MDI)
|
19 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
39 Participants
n=206 Participants
|
|
Hemoglobin A1C Level in Participants
<=10 percent (%)
|
19 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
37 Participants
n=206 Participants
|
|
Hemoglobin A1C Level in Participants
>10 %
|
23 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
48 Participants
n=206 Participants
|
|
Baseline daily total insulin
|
0.87 International units per kilogram (IU/kg)
STANDARD_DEVIATION 0.315 • n=99 Participants
|
0.84 International units per kilogram (IU/kg)
STANDARD_DEVIATION 0.264 • n=107 Participants
|
0.86 International units per kilogram (IU/kg)
STANDARD_DEVIATION 0.289 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Change was calculated by subtracting baseline value from Week 12 value. Least Square (LS) mean changes from baseline were obtained from mixed model repeated measures (MMRM) model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week-4 A1C (\<=10%, \>10%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline A1C-by-time interaction as a covariate.
Outcome measures
| Measure |
Placebo
n=34 Participants
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
|
Sotagliflozin 400 mg
n=40 Participants
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Hemoglobin A1C (A1C) at Week 12
|
-0.99 percentage of A1C
Standard Error 0.149
|
-1.33 percentage of A1C
Standard Error 0.143
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Analysis included participants from the mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.
The daily bolus and basal insulin doses were calculated as an average of the doses over 3 to 5 days before each visit (Baseline and Week 12). Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from MMRM model.
Outcome measures
| Measure |
Placebo
n=34 Participants
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
|
Sotagliflozin 400 mg
n=40 Participants
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Total Daily Bolus Insulin Dose and Total Daily Basal Insulin Dose at Week 12
Total Daily Bolus Insulin Dose
|
-2.96 International Units per day (IU/day)
Standard Error 1.945
|
-4.89 International Units per day (IU/day)
Standard Error 1.832
|
|
Change From Baseline in Total Daily Bolus Insulin Dose and Total Daily Basal Insulin Dose at Week 12
Total Daily Basal Insulin Dose
|
3.26 International Units per day (IU/day)
Standard Error 1.262
|
2.03 International Units per day (IU/day)
Standard Error 1.211
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
A 2-hour PPG sample (plasma) was obtained 2-hours after a standardized Mixed Meal at Baseline (Day 1) and at the visit at Week 12. At Week 12, study drug was to be given within 15 minutes before liquid "Boost®," "Ensure®," or similar nutrition drink product; at baseline, study drug was to be given after the 2-hour post-Mixed Meal PPG sample. Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from analysis of covariance (ANCOVA) model.
Outcome measures
| Measure |
Placebo
n=32 Participants
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
|
Sotagliflozin 400 mg
n=36 Participants
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
|
|---|---|---|
|
Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Standardized Mixed Meal at Week 12
|
0.2 milligrams per deciliter (mg/dL)
Standard Error 12.24
|
-56.4 milligrams per deciliter (mg/dL)
Standard Error 11.61
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
Glycemic instability (mg/dL\*minutes/1000) by hyperglycemia/hypoglycemia was measured by CGM AUC outside target range (as a daily average over the week prior to the visit \[Baseline and Week 12\]) over 24 hours, where outside target range was defined as CGM glucose AUC \>150 mg/dL (hyperglycemia) and CGM glucose AUC \<70 mg/dL (hypoglycemia). Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from MMRM model.
Outcome measures
| Measure |
Placebo
n=28 Participants
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
|
Sotagliflozin 400 mg
n=27 Participants
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Glycemic Instability by Hyperglycemia (Continuous Glucose Monitoring [CGM] Area Under the Curve [AUC] >150 mg/dL) and Hypoglycemia (CGM AUC <70 mg/dL) Over a 24-hour Period at Week 12
Glycemic Instability by Hyperglycemia
|
-5.035 mg/dL*minutes/1000
Standard Error 7.9092
|
-27.338 mg/dL*minutes/1000
Standard Error 8.0100
|
|
Change From Baseline in Glycemic Instability by Hyperglycemia (Continuous Glucose Monitoring [CGM] Area Under the Curve [AUC] >150 mg/dL) and Hypoglycemia (CGM AUC <70 mg/dL) Over a 24-hour Period at Week 12
Glycemic Instability by Hypoglycemia
|
0.221 mg/dL*minutes/1000
Standard Error 0.2508
|
0.428 mg/dL*minutes/1000
Standard Error 0.2528
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
Hypoglycemic event by SMBG was defined as an event in which the fingerstick measurement was \<=70 mg/dL. The number of hypoglycemic events per day was calculated as a daily average number of episodes over the week prior to visit (Baseline and Week 12). Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from MMRM model.
Outcome measures
| Measure |
Placebo
n=35 Participants
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
|
Sotagliflozin 400 mg
n=40 Participants
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Number of Hypoglycemic Events/Day (<=70 mg/dL) by Self-Monitored Blood Glucose (SMBG) at Week 12
|
-0.042 events/day
Standard Error 0.0408
|
-0.001 events/day
Standard Error 0.0379
|
Adverse Events
Placebo
Serious events: 3 serious events
Other events: 16 other events
Deaths: 0 deaths
Sotagliflozin 400 mg
Serious events: 2 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=42 participants at risk
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
|
Sotagliflozin 400 mg
n=43 participants at risk
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
2.4%
1/42 • Number of events 1 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
0.00%
0/43 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/42 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
2.3%
1/43 • Number of events 1 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
2.4%
1/42 • Number of events 1 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
0.00%
0/43 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
4.8%
2/42 • Number of events 2 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
2.3%
1/43 • Number of events 1 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/42 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
2.3%
1/43 • Number of events 1 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Nervous system disorders
Hypoglycaemic unconsciousness
|
2.4%
1/42 • Number of events 1 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
0.00%
0/43 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
Other adverse events
| Measure |
Placebo
n=42 participants at risk
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
|
Sotagliflozin 400 mg
n=43 participants at risk
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/42 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
7.0%
3/43 • Number of events 3 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Investigations
Blood ketone body increased
|
7.1%
3/42 • Number of events 3 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
18.6%
8/43 • Number of events 17 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.4%
1/42 • Number of events 1 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
7.0%
3/43 • Number of events 3 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
9.5%
4/42 • Number of events 4 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
11.6%
5/43 • Number of events 6 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
7.1%
3/42 • Number of events 4 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
2.3%
1/43 • Number of events 1 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.1%
3/42 • Number of events 3 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
4.7%
2/43 • Number of events 2 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
2.4%
1/42 • Number of events 1 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
7.0%
3/43 • Number of events 4 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
3/42 • Number of events 3 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
4.7%
2/43 • Number of events 2 • All Adverse Events (AEs) were collected from Baseline (Day 1) until the end of study (up to Week 12).
Analysis was performed on Safety Population defined as all randomly assigned participants who have taken at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
- Publication restrictions are in place
Restriction type: OTHER