Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: To demonstrate the superiority of sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1C (HbA1c) reduction in participants with type 2 diabetes mellitus (T2D) who have inadequate glycemic control on basal insulin alone or with oral antidiabetes drugs (OADs). Secondary Objectives: * To assess the effects of sotagliflozin 400 mg versus placebo on fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), and HbA1c. * To assess the effects of sotagliflozin 200 mg versus placebo on HbA1c, body weight, FPG, and SBP. * To evaluate the safety of sotagliflozin 400 and 200 mg versus placebo.
Detailed description
Up to 60 weeks (Screening phase of up to 2 weeks, a 4-week Lantus titration/single-blind placebo Run-in phase), a 52-week double blind Treatment Period, and a 2-week post-treatment Follow-up Period.
Interventions
DRUGSotagliflozin
Pharmaceutical form: Tablet Route of administration: Oral
Pharmaceutical form: Solution Route of administration: Subcutaneous
DRUGPlacebo
Pharmaceutical form: Tablet Route of administration: Oral
DRUGOral Antidiabetes Drugs (OADs)
OADs (including metformin) as prescribed by the investigator as per local labeling.
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 with Type 2 Diabetes Mellitus (T2DM) using any types of basal insulin alone or in combination with up to 2 OADs. * Participants have given written informed consent to participate in the study in accordance with local regulations.
Exclusion criteria
* At the time of Screening age \<18 years or \<legal age of majority, whichever is greater. * Type 1 diabetes mellitus. * Oral antidiabetic drugs dose not stable for 8 weeks before Screening. * Use of basal insulin therapy (e.g., insulin glargine, Neutral Protamine Hagedorn (NPH), detemir, or degludec) for less than 6 months before Screening. * Dose of basal insulin (e.g., insulin glargine, NPH, detemir, or degludec) not stable for 8 weeks before Screening (i.e., total daily insulin dose increased or decreased by more than 20%). * Known unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema that is likely to require laser, surgical treatment during study period. * Use of injectable diabetes drugs other than basal insulin (e.g., insulin glargine, NPH, detemir, or degludec), i.e., prandial or rapid-acting insulins, short-acting insulins, glucagon-like peptide 1 (GLP-1) receptor agonists, or inhaled prandial insulin (Afrezza) within 8 weeks of Screening. * Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the trial. * Use of systemic glucocorticoids (excluding topical, intra articular, or ophthalmic application, nasal spray or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit. * Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease 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. * Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization. * Known presence of factors that interfere with the Central Lab HbA1c measurement (e.g., genetic hemoglobin (Hb) variants) compromising the reliability of HbA1c assessment or medical conditions that affect interpretation of HbA1c results (e.g., blood transfusion or severe blood loss in the last 3 months prior to randomization, any condition that shortens erythrocyte survival). * Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from prior to Screening, whichever is longer. * Participants unwilling to perform self-monitoring of blood glucose (SMBG), complete the patient diary, or comply with study visits and other study procedures as required per protocol. * HbA1c \<7.5% or HbA1c \>10.5% measured by the central laboratory at Screening. * HbA1c \<7% measured by the central laboratory at Visit 5 (Week -1). * History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit. * Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women. * Women of childbearing potential not willing to use highly effective 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. * Mean of 3 separate blood pressure measurements \>180 mmHg (systolic blood pressure \[SBP\]) or \>100 mmHg (diastolic blood pressure \[DBP\]). * History of gastric surgery including history of gastric banding or inflammatory bowel disease within 3 years prior to the Screening Visit. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>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). The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 18 | Baseline and Week 18 | An analysis of covariance (ANCOVA) model was used for the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 | Baseline and Week 18 | FPG was performed in fasting state, that is, without any food intake (except for water) for at least 8 hours. An ANCOVA model was used for the analysis. |
| Change From Baseline in Body Weight at Week 18 | Baseline and Week 18 | An ANCOVA model was used for the analysis. |
| Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg at Week 12 | Baseline and Week 12 | An ANCOVA model was used for the analysis. Here, N is the number of participants with data available at a given time point. |
| Change From Baseline in HbA1c at Week 52 | Baseline and Week 52 | An ANCOVA model was used for the analysis. |
| Change From Baseline in Body Weight at Week 52 | Baseline and Week 52 | An ANCOVA model was used for the analysis. |
| Percentage of Participants With Adverse Events (AEs) | First dose of study drug to last dose of study drug (up to 55.7 weeks) + 2 weeks | An AE is any untoward medical occurrence in a participants or clinical investigation participants administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Change From Baseline in SBP at Week 12 for All Participants | Baseline to Week 12 | An ANCOVA model was used for the analysis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hypoglycemic Events | Up to 55.7 weeks | 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 \[typical symptoms of hypoglycemia and plasma glucose ≤ 70 mg/dL\]. |
Countries
Bulgaria, Canada, Czechia, France, Hungary, Slovakia, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 101 investigative sites in the United States, Bulgaria, Canada, Czech Republic, France, Hungary, Slovakia, the United Kingdom from 15 September 2017 to 27 September 2019.
Pre-assignment details
Participants with a diagnosis of Type 2 Diabetes Mellitus were enrolled in 1 of 3 treatment groups, placebo, sotagliflozin 200 milligrams (mg) and sotagliflozin 400 mg. Participants were randomized at a ratio of 1:1:2 respectively to 1 of 3 groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Following a 4-week run-in period, participants were randomized to receive matching placebo to sotagliflozin 200 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 55.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study. | 144 |
| Sotagliflozin 200 mg Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 54.7 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study. | 141 |
| Sotagliflozin 400 mg Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 54.6 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study. | 286 |
| Total | 571 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 6 |
| Overall Study | At the Participant's Own Request | 10 | 5 | 21 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Poor Compliance to Protocol | 0 | 0 | 1 |
| Overall Study | Reason Not Specified | 3 | 4 | 8 |
Baseline characteristics
| Characteristic | Sotagliflozin 200 mg | Placebo | Total | Sotagliflozin 400 mg |
|---|---|---|---|---|
| Age, Continuous | 62.1 years STANDARD_DEVIATION 10.2 | 62.2 years STANDARD_DEVIATION 8.9 | 62.4 years STANDARD_DEVIATION 9.4 | 62.7 years STANDARD_DEVIATION 9.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 12 Participants | 79 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 113 Participants | 129 Participants | 481 Participants | 239 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 11 Participants | 5 Participants |
| Hemoglobin A1c (HbA1c) | 8.76 percentage of HbA1c STANDARD_DEVIATION 0.83 | 8.76 percentage of HbA1c STANDARD_DEVIATION 0.79 | 8.72 percentage of HbA1c STANDARD_DEVIATION 0.8 | 8.69 percentage of HbA1c STANDARD_DEVIATION 0.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 9 Participants | 16 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 10 Participants | 47 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | 23 Participants | 13 Participants |
| Race (NIH/OMB) White | 124 Participants | 117 Participants | 475 Participants | 234 Participants |
| Region of Enrollment Bulgaria | 13 participants | 9 participants | 57 participants | 35 participants |
| Region of Enrollment Canada | 6 participants | 7 participants | 29 participants | 16 participants |
| Region of Enrollment Czechia | 11 participants | 14 participants | 49 participants | 24 participants |
| Region of Enrollment France | 8 participants | 8 participants | 30 participants | 14 participants |
| Region of Enrollment Hungary | 13 participants | 12 participants | 46 participants | 21 participants |
| Region of Enrollment Slovakia | 21 participants | 24 participants | 77 participants | 32 participants |
| Region of Enrollment United Kingdom | 0 participants | 0 participants | 4 participants | 4 participants |
| Region of Enrollment United States | 69 participants | 70 participants | 279 participants | 140 participants |
| Sex: Female, Male Female | 65 Participants | 58 Participants | 255 Participants | 132 Participants |
| Sex: Female, Male Male | 76 Participants | 86 Participants | 316 Participants | 154 Participants |
| Systolic Blood Pressure (SBP) | 136.40 millimeter of Mercury (mmHg) STANDARD_DEVIATION 15.54 | 137.59 millimeter of Mercury (mmHg) STANDARD_DEVIATION 14.12 | 136.42 millimeter of Mercury (mmHg) STANDARD_DEVIATION 14.89 | 135.84 millimeter of Mercury (mmHg) STANDARD_DEVIATION 14.95 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 144 | 1 / 141 | 6 / 285 |
| other Total, other adverse events | 30 / 144 | 18 / 141 | 45 / 285 |
| serious Total, serious adverse events | 16 / 144 | 19 / 141 | 28 / 285 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 18
An analysis of covariance (ANCOVA) model was used for the analysis.
Time frame: Baseline and Week 18
Population: Intent-to-treat (ITT) population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple 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 18 | -0.27 percentage of HbA1c | Standard Error 0.073 |
| Sotagliflozin 200 mg | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 18 | -0.72 percentage of HbA1c | Standard Error 0.073 |
| Sotagliflozin 400 mg | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 18 | -0.81 percentage of HbA1c | Standard Error 0.056 |
Comparison: The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline HbA1c as a covariate.p-value: <0.000195% CI: [-0.638, -0.271]ANCOVA
Comparison: The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline HbA1c as a covariate.p-value: <0.000195% CI: [-0.706, -0.387]ANCOVA
Secondary
Change From Baseline in Body Weight at Week 18
An ANCOVA model was used for the analysis.
Time frame: Baseline and Week 18
Population: ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple 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 18 | 0.36 kilogram (kg) | Standard Error 0.249 |
| Sotagliflozin 200 mg | Change From Baseline in Body Weight at Week 18 | -0.73 kilogram (kg) | Standard Error 0.25 |
| Sotagliflozin 400 mg | Change From Baseline in Body Weight at Week 18 | -1.37 kilogram (kg) | Standard Error 0.19 |
Comparison: The change from baseline to Week 18 is analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline body weight as a covariate.p-value: 0.000795% CI: [-1.716, -0.462]ANCOVA
Comparison: The change from baseline to Week 18 is analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline body weight as a covariate.p-value: <0.000195% CI: [-2.274, -1.183]ANCOVA
Secondary
Change From Baseline in Body Weight at Week 52
An ANCOVA model was used for the analysis.
Time frame: Baseline and Week 52
Population: ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple 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 52 | -0.18 kg | Standard Error 0.579 |
| Sotagliflozin 200 mg | Change From Baseline in Body Weight at Week 52 | -1.19 kg | Standard Error 0.62 |
| Sotagliflozin 400 mg | Change From Baseline in Body Weight at Week 52 | -0.83 kg | Standard Error 0.374 |
Comparison: The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline body weight as a covariate.p-value: 0.246695% CI: [-2.707, 0.696]ANCOVA
Comparison: The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline body weight as a covariate.p-value: 0.33295% CI: [-1.969, 0.665]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18
FPG was performed in fasting state, that is, without any food intake (except for water) for at least 8 hours. An ANCOVA model was used for the analysis.
Time frame: Baseline and Week 18
Population: ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple 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 18 | 12.882 milligram per deciliter (mg/dL) | Standard Error 3.6045 |
| Sotagliflozin 200 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 | -2.975 milligram per deciliter (mg/dL) | Standard Error 3.6083 |
| Sotagliflozin 400 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 | -8.949 milligram per deciliter (mg/dL) | Standard Error 2.755 |
Comparison: The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline FPG as a covariate.p-value: 0.000695% CI: [-24.8845, -6.8309]ANCOVA
Comparison: The change from baseline to Week 18 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline FPG as a covariate.p-value: <0.000195% CI: [-29.7725, -13.8911]ANCOVA
Secondary
Change From Baseline in HbA1c at Week 52
An ANCOVA model was used for the analysis.
Time frame: Baseline and Week 52
Population: ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c at Week 52 | 0.00 percentage of HbA1c | Standard Error 0.279 |
| Sotagliflozin 200 mg | Change From Baseline in HbA1c at Week 52 | -0.52 percentage of HbA1c | Standard Error 0.152 |
| Sotagliflozin 400 mg | Change From Baseline in HbA1c at Week 52 | -0.57 percentage of HbA1c | Standard Error 0.114 |
Comparison: The change from baseline to Week 52 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline HbA1c as a covariate.p-value: 0.126595% CI: [-1.185, 0.147]ANCOVA
Comparison: The change from baseline to Week 52 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline HbA1c as a covariate.p-value: 0.07495% CI: [-1.199, 0.055]ANCOVA
Secondary
Change From Baseline in SBP at Week 12 for All Participants
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 12
Population: ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple 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 | -0.21 mmHg | Standard Error 1.12 |
| Sotagliflozin 200 mg | Change From Baseline in SBP at Week 12 for All Participants | -5.15 mmHg | Standard Error 1.117 |
| Sotagliflozin 400 mg | Change From Baseline in SBP at Week 12 for All Participants | -4.10 mmHg | Standard Error 0.867 |
Comparison: The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline SBP as a covariate.95% CI: [-7.73, -2.142]
Comparison: The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of mean SBP (\<130, ≥130 mmHg) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.001895% CI: [-6.333, -1.448]ANCOVA
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg at Week 12
An ANCOVA model was used for the analysis. Here, N is the number of participants with data available at a given time point.
Time frame: Baseline and Week 12
Population: Analysis population included participants with baseline SBP ≥ 130 mmHg in ITT population where, ITT population included all randomized participants irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout multiple imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg at Week 12 | -4.67 mmHg | Standard Error 1.47 |
| Sotagliflozin 200 mg | Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg at Week 12 | -8.58 mmHg | Standard Error 1.447 |
| Sotagliflozin 400 mg | Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg at Week 12 | -8.50 mmHg | Standard Error 1.103 |
Comparison: The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.0495% CI: [-7.642, -0.178]ANCOVA
Comparison: The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at Week -1, randomization strata of sulfonylureas use (yes, no) at Week -1, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.023995% CI: [-7.161, -0.507]ANCOVA
Secondary
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participants or clinical investigation participants administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: First dose of study drug to last dose of study drug (up to 55.7 weeks) + 2 weeks
Population: Safety population included all randomized participants who received at least 1 dose of double-blind investigational medicinal product (IMP) (regardless of the amount of treatment administered).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Adverse Events (AEs) | 64.6 percentage of participants |
| Sotagliflozin 200 mg | Percentage of Participants With Adverse Events (AEs) | 54.6 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Adverse Events (AEs) | 59.3 percentage of participants |
Other Pre-specified
Percentage of Participants With Hypoglycemic Events
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 \[typical symptoms of hypoglycemia and plasma glucose ≤ 70 mg/dL\].
Time frame: Up to 55.7 weeks
Population: Safety population included all randomised participants who received at least 1 dose of double-blind investigational medicinal product (IMP) (regardless of the amount of treatment administered).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Hypoglycemic Events | Severe or documented symptomatic hypoglycemia | 44.4 percentage of participants |
| Placebo | Percentage of Participants With Hypoglycemic Events | Documented symptomatic hypoglycemia | 44.4 percentage of participants |
| Placebo | Percentage of Participants With Hypoglycemic Events | Any hypoglycemia | 62.5 percentage of participants |
| Sotagliflozin 200 mg | Percentage of Participants With Hypoglycemic Events | Severe or documented symptomatic hypoglycemia | 41.8 percentage of participants |
| Sotagliflozin 200 mg | Percentage of Participants With Hypoglycemic Events | Any hypoglycemia | 56.0 percentage of participants |
| Sotagliflozin 200 mg | Percentage of Participants With Hypoglycemic Events | Documented symptomatic hypoglycemia | 41.8 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Severe or documented symptomatic hypoglycemia | 46 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Documented symptomatic hypoglycemia | 46 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Any hypoglycemia | 62.8 percentage of participants |