Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: To demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo on hemoglobin A1c (HbA1c) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control on diet and exercise. Secondary Objectives: * To compare Sotagliflozin 400 mg versus placebo based on: * Change from baseline in 2-hour postprandial glucose (PPG) following a mixed meal. * Change from baseline in fasting plasma glucose (FPG). * Change from baseline in systolic blood pressure (SBP) for participants with baseline SBP ≥130 millimeter per mercury (mmHg). * Change from baseline in SBP for all participants. * Change from baseline in body weight. * Proportion of participants with HbA1c \<6.5%, \<7.0%. * To compare Sotagliflozin 200 mg versus placebo based on: * Change from baseline in HbA1c. * Change from baseline in 2-hour postprandial glucose (PPG) following a mixed meal. * Change from baseline in body weight. * Change from baseline in SBP for all participants. * To evaluate the safety of Sotagliflozin 400 and 200 mg versus placebo.
Detailed description
Up to 34 weeks, including a Screening Period consisting of a Screening Phase of up to 2 weeks and a 2-week single-blind placebo Run-in Phase, a 26-week double-blind Treatment Period, and a 4-week post-treatment Follow-up visit to collect safety information.
Interventions
Pharmaceutical form: tablet; Route of administration: oral
DRUGPlacebo
Pharmaceutical form: tablet; Route of administration: oral
Sponsors
Sanofi
Lexicon Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Participants (male and female) with T2D, who are treated with diet and exercise only during the 12 weeks prior to screening. * Signed written informed consent.
Exclusion criteria
* Age \<18 years at Screening or \< legal age of majority, whichever is greater. * Type 1 diabetes mellitus. * Body Mass Index (BMI) ≤20 or \>45 kilogram per meter square (kg/m\^2) at Screening. * Hemoglobin A1c (HbA1c) \<7% or \>10% via central laboratory test at Screening. * Fasting plasma glucose (FPG) \>15 millimole per liter (mmol/L) (270 milligram per deciliter \[mg/dL\]) measured by the central laboratory at screening (Visit 1) and confirmed by a repeat test (\>15 mmol/L \[270 mg/dL\]) before randomization. * Women of childbearing potential not willing to use highly effective contraceptive method(s) of birth control during the study treatment period and the follow up period or who are unwilling or unable to be tested for pregnancy during the study. * Treated with an antidiabetic pharmacological agent within the 12 weeks prior to the Screening Visit. * Previous use of any types of insulin for \>1 month (at any time, except for treatment of gestational diabetes). * History of gastric surgical procedure including gastric banding within 3 years before the Screening Visit. * History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit. * Mean of 3 separate blood pressure measurements \>180 millimeter of mercury (mmHg) (systolic) or \>100 mmHg (diastolic). * History of hypertensive emergency within 12 weeks prior to Screening. * Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association \[NYHA\] IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or participants with short life expectancy that, according to the Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult. * Aspartate aminotransferase and/or alanine aminotransferase: \>3 times the upper limit of the normal laboratory range. * Total bilirubin: \>1.5 times the upper limit of the normal laboratory range (except in case of Gilbert's syndrome). * Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit. * Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from screening or randomization, whichever is longer. Current enrollment in any other clinical study involving an investigational study treatment or any other type of medical research. * Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women. * Severe renal disease as defined by estimated glomerular filtration rate (eGFR) of \<30 millimeter per minute (mL/min)/1.73 meter square (m\^2)² at screening by the 4 variable Modification of Diet in Renal Disease (MDRD) equation. * Participant is unwilling or unable to perform self-monitoring of blood glucose (SMBG), complete the participants diary, or comply with study visits and other study procedures as required per protocol. * Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization. The above information is not intended to contain all considerations relevant to a Participant potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 (Sotagliflozin 400 mg Versus Placebo) | Baseline to Week 26 | An analysis of covariance (ANCOVA) model was used for the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 400 mg Versus Placebo) | Baseline to Week 26 | An ANCOVA model was used for the analysis. |
| Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 200 mg Versus Placebo) | Baseline to Week 26 | An ANCOVA model was used for the analysis. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 (Sotagliflozin 400 mg Versus Placebo) | Baseline to Week 26 | An ANCOVA model was used for the analysis. |
| Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥130 Millimeter of Mercury (mmHg) (Sotagliflozin 400 mg Versus Placebo) | Baseline to Week 12 | An ANCOVA model was used for the analysis. |
| Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 400 mg Versus Placebo) | Baseline to Week 12 | An ANCOVA model was used for the analysis. |
| Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 200 mg Versus Placebo) | Baseline to Week 12 | An ANCOVA model was used for the analysis. |
| Percentage of Participants With HbA1c <7.0% at Week 26 (Sotagliflozin 400 mg Versus Placebo) | Week 26 | — |
| Change From Baseline in HbA1c at Week 26 (Sotagliflozin 200 mg Versus Placebo) | Baseline to Week 26 | An ANCOVA model was used for the analysis. |
| Change From Baseline in Body Weight at Week 26 (Sotagliflozin 400 mg Versus Placebo) | Baseline to Week 26 | An ANCOVA model was used for the analysis. |
| Change From Baseline in Body Weight at Week 26 (Sotagliflozin 200 mg Versus Placebo) | Baseline to Week 26 | An ANCOVA model was used for the analysis. |
| Percentage of Participants With HbA1c <6.5% at Week 26 (Sotagliflozin 400 mg Versus Placebo) | Week 26 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo) | Week 26 | 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. |
| Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo) | Week 26 | 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. |
Countries
Canada, Mexico, United States
Participant flow
Recruitment details
Participants took part in the study at 70 investigative sites in the United States, Canada, Mexico, from 11 November 2016 to 17 May 2019.
Pre-assignment details
Participants with a diagnosis of Type 2 Diabetes Mellitus were enrolled in 1 of 3 treatment groups: Placebo, Sotagliflozin 400 milligrams (mg) or Sotagliflozin 200 mg.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Following a 2-week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, QD, before the first meal of the day in the double-blind treatment period for up to 26 weeks. | 150 |
| Sotagliflozin 400 mg Following a 2-week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg tablets, QD, before the first meal of the day in the double-blind treatment period for up to 26 weeks. | 142 |
| Sotagliflozin 200 mg Following a 2-week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, QD, before the first meal of the day in the double-blind treatment period for up to 26 weeks. | 107 |
| Total | 399 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 |
| Overall Study | At the Participant's own Request | 11 | 5 | 8 |
| Overall Study | Lost to Follow-up | 4 | 5 | 0 |
| Overall Study | Poor Compliance to Protocol | 1 | 0 | 0 |
| Overall Study | Reason not Specified | 3 | 4 | 2 |
Baseline characteristics
| Characteristic | Total | Sotagliflozin 200 mg | Sotagliflozin 400 mg | Placebo |
|---|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 11.3 | 52.3 years STANDARD_DEVIATION 11.4 | 54.7 years STANDARD_DEVIATION 11.2 | 55.3 years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 253 Participants | 69 Participants | 85 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 144 Participants | 36 Participants | 57 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Hemoglobin A1c (HbA1c) | 8.09 percentage of HbA1c STANDARD_DEVIATION 0.87 | 8.00 percentage of HbA1c STANDARD_DEVIATION 0.81 | 8.14 percentage of HbA1c STANDARD_DEVIATION 0.92 | 8.11 percentage of HbA1c STANDARD_DEVIATION 0.88 |
| Race (NIH/OMB) American Indian or Alaska Native | 18 Participants | 3 Participants | 3 Participants | 12 Participants |
| Race (NIH/OMB) Asian | 24 Participants | 11 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 12 Participants | 18 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 306 Participants | 77 Participants | 117 Participants | 112 Participants |
| Region of Enrollment Canada | 31 participants | 7 participants | 13 participants | 11 participants |
| Region of Enrollment Mexico | 109 participants | 37 participants | 29 participants | 43 participants |
| Region of Enrollment United States | 259 participants | 63 participants | 100 participants | 96 participants |
| Sex: Female, Male Female | 193 Participants | 53 Participants | 68 Participants | 72 Participants |
| Sex: Female, Male Male | 206 Participants | 54 Participants | 74 Participants | 78 Participants |
| Systolic Blood Pressure (SBP) | 128.00 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.7 | 128.08 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.08 | 128.70 millimeter of mercury (mmHg) STANDARD_DEVIATION 4.8 | 127.27 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.08 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 150 | 0 / 142 | 0 / 107 |
| other Total, other adverse events | 20 / 150 | 17 / 142 | 14 / 107 |
| serious Total, serious adverse events | 3 / 150 | 3 / 142 | 2 / 107 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 (Sotagliflozin 400 mg Versus Placebo)
An analysis of covariance (ANCOVA) model was used for the analysis.
Time frame: Baseline to Week 26
Population: Participants in the Intent-to-treat (ITT) population who were randomized to Sotagliflozin 400 mg and Placebo under original Protocol and Protocol Amendment 1. Missing data are imputed using washout imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 (Sotagliflozin 400 mg Versus Placebo) | -0.34 percentage of HbA1c | Standard Error 0.12 |
| Sotagliflozin 400 mg | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 (Sotagliflozin 400 mg Versus Placebo) | -1.03 percentage of HbA1c | Standard Error 0.122 |
Comparison: The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.p-value: <0.000195% CI: [-0.975, -0.415]ANCOVA
Secondary
Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 200 mg Versus Placebo)
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Population: Participants in the ITT population who were randomized to Sotagliflozin 200 mg and Placebo under Protocol Amendment 1. Missing data are imputed using washout imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 200 mg Versus Placebo) | -0.500 mmol/L | Standard Error 0.2443 |
| Sotagliflozin 400 mg | Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 200 mg Versus Placebo) | -0.847 mmol/L | Standard Error 0.2477 |
Comparison: The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups under Amendment 1 randomization strata of HbA1c (≤8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, country, treatment-by-country as fixed effects, and baseline HbA1c as a covariate.p-value: 0.208195% CI: [-0.8853, 0.1928]ANCOVA
Secondary
Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 400 mg Versus Placebo)
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Population: Participants in the ITT population who were randomized to Sotagliflozin 400 mg and Placebo under original Protocol and Protocol Amendment 1. Missing data are imputed using washout imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 400 mg Versus Placebo) | -0.591 millimole per liter (mmol/L) | Standard Error 0.1943 |
| Sotagliflozin 400 mg | Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 400 mg Versus Placebo) | -1.156 millimole per liter (mmol/L) | Standard Error 0.1964 |
Comparison: The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups randomization strata of HbA1c (≤8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, country, treatment-by-country as fixed effects, and baseline HbA1c as a covariate.p-value: 0.014195% CI: [-1.0166, -0.114]ANCOVA
Secondary
Change From Baseline in Body Weight at Week 26 (Sotagliflozin 200 mg Versus Placebo)
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Population: Participants in the ITT population who were randomized to Sotagliflozin 200 mg and Placebo under Protocol Amendment 1. Missing data are imputed using washout imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at Week 26 (Sotagliflozin 200 mg Versus Placebo) | -0.52 kg | Standard Error 0.509 |
| Sotagliflozin 400 mg | Change From Baseline in Body Weight at Week 26 (Sotagliflozin 200 mg Versus Placebo) | -1.69 kg | Standard Error 0.518 |
Comparison: The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, ≥130mmHg) at screening, and country as fixed effects, and baseline weight as a covariate.p-value: 0.040695% CI: [-2.281, -0.05]ANCOVA
Secondary
Change From Baseline in Body Weight at Week 26 (Sotagliflozin 400 mg Versus Placebo)
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Population: Participants in the ITT population who were randomized to Sotagliflozin 400 mg and Placebo under original Protocol and Protocol Amendment 1. Missing data are imputed using washout imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at Week 26 (Sotagliflozin 400 mg Versus Placebo) | -0.79 kilogram (Kg) | Standard Error 0.373 |
| Sotagliflozin 400 mg | Change From Baseline in Body Weight at Week 26 (Sotagliflozin 400 mg Versus Placebo) | -2.33 kilogram (Kg) | Standard Error 0.379 |
Comparison: The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline weight as a covariate.p-value: 0.000595% CI: [-2.404, -0.676]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 (Sotagliflozin 400 mg Versus Placebo)
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Population: Participants in the ITT population who were randomized to Sotagliflozin 400 mg and Placebo under original Protocol and Protocol Amendment 1.Missing data are imputed using washout imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 (Sotagliflozin 400 mg Versus Placebo) | -0.201 mmol/L | Standard Error 0.2739 |
| Sotagliflozin 400 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 (Sotagliflozin 400 mg Versus Placebo) | -1.756 mmol/L | Standard Error 0.2719 |
Comparison: The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, ≥ 130mmHg) at screening, and country as fixed effects, and baseline fasting plasma glucose as a covariate.p-value: <0.000195% CI: [-2.1876, -0.9234]ANCOVA
Secondary
Change From Baseline in HbA1c at Week 26 (Sotagliflozin 200 mg Versus Placebo)
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Population: Participants in the ITT population who were randomized to Sotagliflozin 200 mg and Placebo under Protocol Amendment 1. Missing data are imputed using washout imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c at Week 26 (Sotagliflozin 200 mg Versus Placebo) | -0.26 percentage of HbA1c | Standard Error 0.143 |
| Sotagliflozin 400 mg | Change From Baseline in HbA1c at Week 26 (Sotagliflozin 200 mg Versus Placebo) | -0.93 percentage of HbA1c | Standard Error 0.148 |
Comparison: The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.p-value: <0.000195% CI: [-0.989, -0.354]ANCOVA
Secondary
Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 200 mg Versus Placebo)
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 12
Population: Participants in the ITT population who were randomized to Sotagliflozin 200 mg and Placebo under Protocol Amendment 1. Missing data are imputed using washout imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 200 mg Versus Placebo) | -1.62 mmHg | Standard Error 1.215 |
| Sotagliflozin 400 mg | Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 200 mg Versus Placebo) | -4.82 mmHg | Standard Error 1.211 |
Comparison: The change from baseline to Week 12 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.019395% CI: [-5.869, -0.518]ANCOVA
Secondary
Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 400 mg Versus Placebo)
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 12
Population: Participants in the ITT population who were randomized to Sotagliflozin 400 mg and Placebo under original Protocol and Protocol Amendment 1. Missing data are imputed using washout imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 400 mg Versus Placebo) | -0.57 mmHg | Standard Error 1.088 |
| Sotagliflozin 400 mg | Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 400 mg Versus Placebo) | -1.35 mmHg | Standard Error 1.116 |
Comparison: The change from baseline to Week 12 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.546795% CI: [-3.311, 1.753]ANCOVA
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥130 Millimeter of Mercury (mmHg) (Sotagliflozin 400 mg Versus Placebo)
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 12
Population: Analysis was performed on participants in the ITT population who were randomized to Sotagliflozin 400 mg and Placebo under original Protocol and Protocol Amendment 1 with Baseline SBP ≥130 mmHg. Missing data are imputed using washout imputation method under the missing not at random framework. This Outcome Measure was pre-specified in the protocol to be assessed in the Placebo and Sotagliflozin 400 mg arms.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥130 Millimeter of Mercury (mmHg) (Sotagliflozin 400 mg Versus Placebo) | -4.45 mmHg | Standard Error 2.419 |
| Sotagliflozin 400 mg | Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥130 Millimeter of Mercury (mmHg) (Sotagliflozin 400 mg Versus Placebo) | -7.96 mmHg | Standard Error 2.282 |
Comparison: The change from baseline to Week 12 is analyzed using analysis ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.0, \>8.0%) at screening and country as fixed effects, and baseline SBP as a covariate.p-value: 0.16895% CI: [-8.478, 1.476]ANCOVA
Secondary
Percentage of Participants With HbA1c <6.5% at Week 26 (Sotagliflozin 400 mg Versus Placebo)
Time frame: Week 26
Population: Participants in the ITT population who were randomized to Sotagliflozin 400 mg and Placebo under original Protocol and Protocol Amendment 1. This Outcome Measure was pre-specified in the protocol to be assessed in the Placebo and Sotagliflozin 400 mg arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With HbA1c <6.5% at Week 26 (Sotagliflozin 400 mg Versus Placebo) | 10.7 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With HbA1c <6.5% at Week 26 (Sotagliflozin 400 mg Versus Placebo) | 23.2 percentage of participants |
Comparison: Percentage difference between treatment groups from each stratum (randomization strata of HbA1c (\<=8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, \>=130 mmHg) at screening) using Cochran-Mantel-Haenszel weights.p-value: 0.003795% CI: [4.18, 21.02]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HbA1c <7.0% at Week 26 (Sotagliflozin 400 mg Versus Placebo)
Time frame: Week 26
Population: Participants in the ITT population who were randomized to Sotagliflozin 400 mg and Placebo under original Protocol and Protocol Amendment 1. This Outcome Measure was pre-specified in the protocol to be assessed in the Placebo and Sotagliflozin 400 mg arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With HbA1c <7.0% at Week 26 (Sotagliflozin 400 mg Versus Placebo) | 28.0 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With HbA1c <7.0% at Week 26 (Sotagliflozin 400 mg Versus Placebo) | 47.2 percentage of participants |
Comparison: Percentage difference between treatment groups from each stratum (randomization strata of HbA1c (\<=8.0, \>8.0%) at screening, randomization strata of mean SBP (\<130, \>=130 mmHg) at screening) using Cochran-Mantel-Haenszel weights.p-value: 0.000795% CI: [8.39, 30]Cochran-Mantel-Haenszel
Other Pre-specified
Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo)
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.
Time frame: Week 26
Population: Participants in the ITT population who were randomized to Sotagliflozin 200 mg and Placebo under Protocol Amendment 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo) | Any hypoglycemia | 2.7 percentage of participants |
| Placebo | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo) | Documented symptomatic hypoglycemia | 0.9 percentage of participants |
| Placebo | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo) | Severe or documented symptomatic hypoglycemia | 0.9 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo) | Documented symptomatic hypoglycemia | 0.9 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo) | Any hypoglycemia | 1.9 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 200 mg Versus Placebo) | Severe or documented symptomatic hypoglycemia | 0.9 percentage of participants |
Other Pre-specified
Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo)
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.
Time frame: Week 26
Population: Participants in the ITT population who were randomized to Sotagliflozin 400 mg and Placebo under original Protocol and Protocol Amendment 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo) | Documented symptomatic hypoglycemia | 1.3 percentage of participants |
| Placebo | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo) | Any hypoglycemia | 2.7 percentage of participants |
| Placebo | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo) | Severe or documented symptomatic hypoglycemia | 1.3 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo) | Any hypoglycemia | 2.1 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo) | Documented symptomatic hypoglycemia | 0.7 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events (Sotagliflozin 400 mg Versus Placebo) | Severe or documented symptomatic hypoglycemia | 0.7 percentage of participants |