Trial Outcomes & Findings for A Phase 3 Study to Evaluate the Safety of Sotagliflozin in Patients With Type 1 Diabetes Who Have Inadequate Glycemic Control With Insulin Therapy Alone (NCT NCT02531035)

Last Updated: 2020-02-12

Results Overview

The primary composite endpoint included blood samples for the assessment of Hemoglobin A1C to determine the participants with a value \<7.0%. A central blinded adjudication process determined whether participants experienced either DKA or Severe Hypoglycemia.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1405 participants

Primary outcome timeframe

Week 24

Results posted on

2020-02-12

Participant Flow

Participants took part in the study at 133 investigative sites across 19 countries: Poland, Slovakia, Spain, United Kingdom, Belgium, Bulgaria, Czech Republic, France, Germany, Hungary, Italy, Argentina, Australia, Canada, Colombia, Israel, New Zealand, South Africa and United States from 18 September 2015 to 18 April 2017.

1405 participants with a diagnosis of Type 1 Diabetes were enrolled equally in 1 of 2 treatment groups: placebo or sotagliflozin 400 milligrams (mg).

Participant milestones

Participant milestones
Measure	Placebo Two placebo-matching to sotagliflozin tablets daily, orally, before the first meal of the day for 24 weeks.	Sotagliflozin 400 mg Sotagliflozin 400 mg (two 200 mg tablets) once daily, orally, before the first meal of the day for 24 weeks.
Overall Study STARTED	705	700
Overall Study Treated	703	699
Overall Study COMPLETED	624	605
Overall Study NOT COMPLETED	81	95

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Two placebo-matching to sotagliflozin tablets daily, orally, before the first meal of the day for 24 weeks.	Sotagliflozin 400 mg Sotagliflozin 400 mg (two 200 mg tablets) once daily, orally, before the first meal of the day for 24 weeks.
Overall Study Death	0	1
Overall Study Protocol Violation	1	1
Overall Study Noncompliance with study drug	8	3
Overall Study Physician Decision	1	0
Overall Study Adverse Event	16	45
Overall Study Other	3	2
Overall Study Withdrawal by Subject	42	32
Overall Study Lost to Follow-up	8	10
Overall Study Randomized, not treated	2	1

Baseline Characteristics

A1C is the measurement of hemoglobin A1C. Data is available for 701 participants in the Placebo arm and 699 participants in the Sotagliflozin arm.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=703 Participants Two placebo-matching to sotagliflozin tablets daily, orally, before the first meal of the day for 24 weeks.	Sotagliflozin 400 mg n=699 Participants Sotagliflozin 400 mg (two 200 mg tablets) once daily, orally, before the first meal of the day for 24 weeks.	Total n=1402 Participants Total of all reporting groups
Age, Continuous	42.4 years STANDARD_DEVIATION 14.04 • n=703 Participants	43.3 years STANDARD_DEVIATION 14.17 • n=699 Participants	42.8 years STANDARD_DEVIATION 14.11 • n=1402 Participants
Sex: Female, Male Female	364 Participants n=703 Participants	341 Participants n=699 Participants	705 Participants n=1402 Participants
Sex: Female, Male Male	339 Participants n=703 Participants	358 Participants n=699 Participants	697 Participants n=1402 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	5 Participants n=703 Participants	1 Participants n=699 Participants	6 Participants n=1402 Participants
Race/Ethnicity, Customized Asian	5 Participants n=703 Participants	7 Participants n=699 Participants	12 Participants n=1402 Participants
Race/Ethnicity, Customized Black or African American	22 Participants n=703 Participants	24 Participants n=699 Participants	46 Participants n=1402 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=703 Participants	1 Participants n=699 Participants	1 Participants n=1402 Participants
Race/Ethnicity, Customized White	621 Participants n=703 Participants	619 Participants n=699 Participants	1240 Participants n=1402 Participants
Race/Ethnicity, Customized Other	37 Participants n=703 Participants	31 Participants n=699 Participants	68 Participants n=1402 Participants
Race/Ethnicity, Customized Not Applicable	13 Participants n=703 Participants	16 Participants n=699 Participants	29 Participants n=1402 Participants
hemoglobin A1C (A1C)	8.21 percentage of A1C STANDARD_DEVIATION 0.921 • n=701 Participants • A1C is the measurement of hemoglobin A1C. Data is available for 701 participants in the Placebo arm and 699 participants in the Sotagliflozin arm.	8.26 percentage of A1C STANDARD_DEVIATION 0.965 • n=699 Participants • A1C is the measurement of hemoglobin A1C. Data is available for 701 participants in the Placebo arm and 699 participants in the Sotagliflozin arm.	8.23 percentage of A1C STANDARD_DEVIATION 0.943 • n=1400 Participants • A1C is the measurement of hemoglobin A1C. Data is available for 701 participants in the Placebo arm and 699 participants in the Sotagliflozin arm.
Body Weight	81.55 kilograms (kg) STANDARD_DEVIATION 17.032 • n=703 Participants	82.40 kilograms (kg) STANDARD_DEVIATION 17.131 • n=699 Participants	81.97 kilograms (kg) STANDARD_DEVIATION 17.081 • n=1402 Participants
Duration of Diabetes	19.6 years STANDARD_DEVIATION 12.07 • n=703 Participants	20.5 years STANDARD_DEVIATION 12.37 • n=699 Participants	20.0 years STANDARD_DEVIATION 12.22 • n=1402 Participants
Baseline Total Daily Insulin	0.71 International units per kilogram (IU/kg) STANDARD_DEVIATION 0.291 • n=703 Participants	0.69 International units per kilogram (IU/kg) STANDARD_DEVIATION 0.276 • n=699 Participants	0.70 International units per kilogram (IU/kg) STANDARD_DEVIATION 0.284 • n=1402 Participants
Body Mass Index (BMI)	28.10 kg/m^2 (kilogram(s)/square meter) STANDARD_DEVIATION 5.183 • n=703 Participants	28.29 kg/m^2 (kilogram(s)/square meter) STANDARD_DEVIATION 5.128 • n=699 Participants	28.19 kg/m^2 (kilogram(s)/square meter) STANDARD_DEVIATION 5.155 • n=1402 Participants

PRIMARY outcome

Timeframe: Week 24

Population: The primary efficacy analyses were based on the modified Intent-to-Treat (mITT) population.

Outcome measures

Outcome measures
Measure	Placebo n=703 Participants Two placebo-matching to sotagliflozin tablets daily, orally, before the first meal of the day for 24 weeks.	Sotagliflozin 400 mg n=699 Participants Sotagliflozin 400 mg (two 200 mg tablets) once daily, orally, before the first meal of the day for 24 weeks.
Percentage of Participants With A1C <7.0% at Week 24 and No Episode of Severe Hypoglycemia and No Episode of Diabetic Ketoacidosis (DKA) After Randomization	15.2 percentage of participants	28.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Analyses included participants from the mITT population. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. Least Squares (LS) means were obtained from a mixed-effects model for repeated measures (MMRM) model including all available post baseline data. A negative change from Baseline (a lower AIC value at Week 24) indicates an improvement.

Outcome measures

Outcome measures
Measure	Placebo n=628 Participants Two placebo-matching to sotagliflozin tablets daily, orally, before the first meal of the day for 24 weeks.	Sotagliflozin 400 mg n=627 Participants Sotagliflozin 400 mg (two 200 mg tablets) once daily, orally, before the first meal of the day for 24 weeks.
Change From Baseline in A1C	-0.33 percentage of A1c Standard Error 0.031	-0.79 percentage of A1c Standard Error 0.032

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Analyses included participants from the mITT population. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model. A negative change from Baseline indicates a loss in body weight from Baseline to Week 24.

Outcome measures

Outcome measures
Measure	Placebo n=633 Participants Two placebo-matching to sotagliflozin tablets daily, orally, before the first meal of the day for 24 weeks.	Sotagliflozin 400 mg n=630 Participants Sotagliflozin 400 mg (two 200 mg tablets) once daily, orally, before the first meal of the day for 24 weeks.
Absolute Change From Baseline in Body Weight	0.77 kilograms (kg) Standard Error 0.122	-2.21 kilograms (kg) Standard Error 0.122

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Participants from mITT population and who had a Baseline SBP \>= 130 mm Hg. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

An automatic sphygmomanometer was used with instructions on blood pressure measurements to allow for standardization. Week 16 was used because the protocol required Investigators to keep participant's hypertensive medications stable between Baseline and Week 16, unless a change was required for safety reasons. Baseline was defined as the last value collected prior to the first does of double-blind study medication. LS means were obtained from MMRM model including all available post baseline values. A negative change indicates a decrease in SBP between Baseline and Week 16.

Outcome measures

Outcome measures
Measure	Placebo n=192 Participants Two placebo-matching to sotagliflozin tablets daily, orally, before the first meal of the day for 24 weeks.	Sotagliflozin 400 mg n=186 Participants Sotagliflozin 400 mg (two 200 mg tablets) once daily, orally, before the first meal of the day for 24 weeks.
Change From Baseline in Systolic Blood Pressure (SBP) in the Subset of Participants With Baseline SBP >=130 Millimeter of Mercury (mmHg)	-5.7 mmHg Standard Error 0.90	-9.2 mmHg Standard Error 0.92

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Analyses included participants from the mITT population. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

The mean bolus insulin dose in international units/day (IU/day) for Week 24 was the average over the 3 to 5 days prior to the Week 24 visit. The Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model including all available post Baseline values. A negative percent change from Baseline indicated a reduction in the amount of bolus insulin used and a positive percent change from Baseline indicated an increase in the amount of bolus insulin used between Baseline and Week 24.

Outcome measures

Outcome measures
Measure	Placebo n=623 Participants Two placebo-matching to sotagliflozin tablets daily, orally, before the first meal of the day for 24 weeks.	Sotagliflozin 400 mg n=617 Participants Sotagliflozin 400 mg (two 200 mg tablets) once daily, orally, before the first meal of the day for 24 weeks.
Percent Change From Baseline in Mean Daily Bolus Insulin Dose	6.62 percent change in IU/day Standard Error 2.272	-5.71 percent change in IU/day Standard Error 2.289

Adverse Events

Placebo

Serious events: 23 serious events

Other events: 70 other events

Deaths: 0 deaths

Sotagliflozin 400 mg

Serious events: 48 serious events

Other events: 70 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=703 participants at risk Two placebo-matching to sotagliflozin tablets daily, orally, before the first meal of the day for 24 weeks.	Sotagliflozin 400 mg n=699 participants at risk Sotagliflozin 400 mg (two 200 mg tablets) once daily, orally, before the first meal of the day for 24 weeks.
Gastrointestinal disorders Diarrhoea	2.4% 17/703 • Number of events 22 • Baseline (Day 1) to 30 days after end of treatment (Up to 28 Weeks) Analysis performed on safety population which includes participants who received at least 1 dose of study drug.	5.0% 35/699 • Number of events 41 • Baseline (Day 1) to 30 days after end of treatment (Up to 28 Weeks) Analysis performed on safety population which includes participants who received at least 1 dose of study drug.
Infections and infestations Viral upper respiratory tract infection	7.8% 55/703 • Number of events 62 • Baseline (Day 1) to 30 days after end of treatment (Up to 28 Weeks) Analysis performed on safety population which includes participants who received at least 1 dose of study drug.	5.9% 41/699 • Number of events 46 • Baseline (Day 1) to 30 days after end of treatment (Up to 28 Weeks) Analysis performed on safety population which includes participants who received at least 1 dose of study drug.

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: [email protected]

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