Trial Outcomes & Findings for Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus on Background of Sulfonylurea Alone or With Metformin (NCT NCT03066830)

Last Updated: 2021-05-11

Results Overview

Missing data are imputed using the retrieved dropouts imputation method. An analysis of covariance (ANCOVA) model was used for the analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

507 participants

Primary outcome timeframe

Baseline to Week 26

Results posted on

2021-05-11

Participant Flow

Participants took part in the study at 76 investigative sites in the United States, Bulgaria, Estonia, Hungary, Republic of Korea, Poland, Romania, Slovakia, Ukraine, United Kingdom from 24 February 2017 to 30 April 2019.

Participants with a diagnosis of Diabetes Mellitus were enrolled equally in 1 of 2 treatment groups, Sotagliflozin 400 milligrams (mg) and Placebo.

Participant milestones

Participant milestones
Measure	Placebo Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Overall Study STARTED	254	253
Overall Study COMPLETED	221	231
Overall Study NOT COMPLETED	33	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Overall Study At the Participant's own Request	16	17
Overall Study Other	3	0
Overall Study Poor Compliance to Protocol	1	0
Overall Study Adverse Event	2	2
Overall Study Lost to Follow-up	11	3

Baseline Characteristics

Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus on Background of Sulfonylurea Alone or With Metformin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=254 Participants Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg n=253 Participants Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Total n=507 Participants Total of all reporting groups
Hemoglobin A1c (HbA1c)	8.18 percentage of HbA1c STANDARD_DEVIATION 0.83 • n=5 Participants	8.20 percentage of HbA1c STANDARD_DEVIATION 0.83 • n=7 Participants	8.19 percentage of HbA1c STANDARD_DEVIATION 0.83 • n=5 Participants
Systolic Blood Pressure (SBP)	133.08 millimeter of mercury (mmHg) STANDARD_DEVIATION 14.21 • n=5 Participants	134.30 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.01 • n=7 Participants	133.69 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.62 • n=5 Participants
Age, Continuous	63.0 years STANDARD_DEVIATION 9.9 • n=5 Participants	63.3 years STANDARD_DEVIATION 8.8 • n=7 Participants	63.1 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	124 Participants n=5 Participants	104 Participants n=7 Participants	228 Participants n=5 Participants
Sex: Female, Male Male	130 Participants n=5 Participants	149 Participants n=7 Participants	279 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	43 Participants n=5 Participants	53 Participants n=7 Participants	96 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	210 Participants n=5 Participants	198 Participants n=7 Participants	408 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	34 Participants n=5 Participants	28 Participants n=7 Participants	62 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) White	211 Participants n=5 Participants	215 Participants n=7 Participants	426 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 26

Population: Intent-to-treat (ITT) population included all randomized participants.

Missing data are imputed using the retrieved dropouts imputation method. An analysis of covariance (ANCOVA) model was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=254 Participants Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg n=253 Participants Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26	0.06 percentage HbA1c Standard Error 0.082	-0.70 percentage HbA1c Standard Error 0.068

SECONDARY outcome

Timeframe: Baseline to Week 26

Population: ITT population included all randomized participants.

Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=254 Participants Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg n=253 Participants Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	0.277 millimole per liter (mmol/L) Standard Error 0.2691	-1.331 millimole per liter (mmol/L) Standard Error 0.1844

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Analysis was performed on ITT population in participants with baseline SBP ≥130 mmHg.

Missing data are imputed using the washout imputation method under the missing, not at random framework. An ANCOVA model was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg n=146 Participants Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg	-3.58 mmHg Standard Error 1.052	-4.41 mmHg Standard Error 1.061

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: ITT population included all randomized participants .

Missing data are imputed using washout imputation method under the missing not at random framework. An ANCOVA model was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=254 Participants Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg n=253 Participants Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Change From Baseline in SBP at Week 12 for All Participants	-0.69 mmHg Standard Deviation 0.826	-1.71 mmHg Standard Deviation 0.830

SECONDARY outcome

Timeframe: Baseline to Week 26

Population: ITT population included all randomized participants.

Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=254 Participants Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg n=253 Participants Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Change From Baseline in Body Weight at Week 26	-0.29 kilogram (kg) Standard Deviation 0.206	-1.70 kilogram (kg) Standard Deviation 0.215

SECONDARY outcome

Timeframe: Week 26

Population: ITT population included all randomized participants.

Outcome measures

Outcome measures
Measure	Placebo n=254 Participants Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg n=253 Participants Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Percentage of Participants With HbA1c <6.5% at Week 26	1.6 percentage of participants	8.3 percentage of participants

SECONDARY outcome

Timeframe: Week 26

Population: ITT population included all randomized participants.

Outcome measures

Outcome measures
Measure	Placebo n=254 Participants Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg n=253 Participants Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Percentage of Participants With HbA1c <7.0% at Week 26	8.7 percentage of participants	26.1 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 79 weeks in the treatment period

Population: Safety population was defined as all randomized participants who had received at least 1 dose of the double-blind investigational medicinal product.

Percentage of participants with hypoglycemic events are reported for the following 3 categories: Any hypoglycemia (as reported in the Electronic Case Report Form); Documented symptomatic hypoglycemia \[typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤ 70 mg/dL (3.9 mmol/L)\]; Severe \[an event requiring assistance of another person to actively administer carbohydrate, glucagon, intravenous glucose or other resuscitative actions\] or documented symptomatic hypoglycemia \[typical symptoms of hypoglycemia and plasma glucose ≤ 70 mg/dL\]. Participants may be reported in more than one category.

Outcome measures

Outcome measures
Measure	Placebo n=253 Participants Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Sotagliflozin 400 mg n=254 Participants Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.
Percentage of Participants With Hypoglycemic Events Any hypoglycemia	22.1 percentage of participants	19.7 percentage of participants
Percentage of Participants With Hypoglycemic Events Documented symptomatic hypoglycemia	13.0 percentage of participants	11.4 percentage of participants
Percentage of Participants With Hypoglycemic Events Severe or documented symptomatic hypoglycemia	13.0 percentage of participants	11.8 percentage of participants

Adverse Events

Placebo

Serious events: 40 serious events

Other events: 90 other events

Deaths: 2 deaths

Sotagliflozin 400 mg

Serious events: 32 serious events

Other events: 71 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=253 participants at risk Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks. One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study is included in the Sotagliflozin 400 mg arm in the safety population.	Sotagliflozin 400 mg n=254 participants at risk Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 milligrams (mg), orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks. One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study is included in the Sotagliflozin 400 mg arm in the safety population.
Gastrointestinal disorders Diarrhoea	4.3% 11/253 • First dose of study drug to last dose of study drug (up to 82.9 weeks) + 2 weeks Safety population included all randomized participants who received at least one dose of double-blind investigational medicinal product (IMP). One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study and summarized in the Sotagliflozin 400 mg arm in the safety population.	8.7% 22/254 • First dose of study drug to last dose of study drug (up to 82.9 weeks) + 2 weeks Safety population included all randomized participants who received at least one dose of double-blind investigational medicinal product (IMP). One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study and summarized in the Sotagliflozin 400 mg arm in the safety population.
Metabolism and nutrition disorders Hyperglycaemia	19.0% 48/253 • First dose of study drug to last dose of study drug (up to 82.9 weeks) + 2 weeks Safety population included all randomized participants who received at least one dose of double-blind investigational medicinal product (IMP). One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study and summarized in the Sotagliflozin 400 mg arm in the safety population.	5.5% 14/254 • First dose of study drug to last dose of study drug (up to 82.9 weeks) + 2 weeks Safety population included all randomized participants who received at least one dose of double-blind investigational medicinal product (IMP). One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study and summarized in the Sotagliflozin 400 mg arm in the safety population.
Infections and infestations Nasopharyngitis	9.1% 23/253 • First dose of study drug to last dose of study drug (up to 82.9 weeks) + 2 weeks Safety population included all randomized participants who received at least one dose of double-blind investigational medicinal product (IMP). One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study and summarized in the Sotagliflozin 400 mg arm in the safety population.	8.3% 21/254 • First dose of study drug to last dose of study drug (up to 82.9 weeks) + 2 weeks Safety population included all randomized participants who received at least one dose of double-blind investigational medicinal product (IMP). One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study and summarized in the Sotagliflozin 400 mg arm in the safety population.
Infections and infestations Upper respiratory tract infection	7.5% 19/253 • First dose of study drug to last dose of study drug (up to 82.9 weeks) + 2 weeks Safety population included all randomized participants who received at least one dose of double-blind investigational medicinal product (IMP). One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study and summarized in the Sotagliflozin 400 mg arm in the safety population.	3.5% 9/254 • First dose of study drug to last dose of study drug (up to 82.9 weeks) + 2 weeks Safety population included all randomized participants who received at least one dose of double-blind investigational medicinal product (IMP). One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study and summarized in the Sotagliflozin 400 mg arm in the safety population.
Infections and infestations Urinary tract infection	3.2% 8/253 • First dose of study drug to last dose of study drug (up to 82.9 weeks) + 2 weeks Safety population included all randomized participants who received at least one dose of double-blind investigational medicinal product (IMP). One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study and summarized in the Sotagliflozin 400 mg arm in the safety population.	7.5% 19/254 • First dose of study drug to last dose of study drug (up to 82.9 weeks) + 2 weeks Safety population included all randomized participants who received at least one dose of double-blind investigational medicinal product (IMP). One participant randomized to Placebo who was dosed with Sotagliflozin 400 mg treatment during the study and summarized in the Sotagliflozin 400 mg arm in the safety population.

Additional Information

Medical Affairs

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Phone: 510-338-6064

Email: [email protected]

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