Chronic Kidney Disease Stage 4, 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 at Week 26 in participants with Type 2 diabetes who have inadequate glycemic control and severe renal impairment Secondary Objectives: * To assess the effects of sotagliflozin 200 mg versus placebo based on change from baseline in HbA1c * To assess the effects of sotagloflozin 400 mg and 200 mg versus placebo * To evaluate the safety of sotagliflozin 400 mg and 200 mg versus placebo
Detailed description
The study duration is up to 60 weeks including 4 weeks prior to randomization, 52 weeks of randomized treatment and a visit 4 weeks after completion of the randomized treatment period.
Interventions
DRUGPlacebo
Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.
DRUGSotagliflozin
Sotagliflozin 200 mg, tablet, orally, once daily.
Sponsors
Sanofi
Lexicon Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Participants with Type 2 Diabetes (drug-naïve or on antidiabetic therapy) and documented severe renal insufficiency - CKD4 - defined by an estimated glomerular filtration rate (eGFR) equation (based on the 4 variable modification of diet in renal disease (MDRD) equation) of ≥15 and \<30 milliliter per minute (mL/min)/1.73 per meter square (m\^2). * Signed written informed consent to participate in the study in accordance with local regulations.
Exclusion criteria
* At the time of screening, age \<18 years. * Hemoglobin A1c (HbA1c) \<7% or \>11%. * Type 1 diabetes. * Women of childbearing potential (WOCBP) 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. * Treatment with an sodium-glucose cotransporter type 2 (SGLT2) inhibitor (canagliflozin, dapagliflozin, empagliflozin) during the last 12 months. * Uncontrolled high blood pressure, severe anemia, severe cardiovascular problems, such as heart failure, active cancer, or other conditions that the Investigator believes with result in a short life expectancy, 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. 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 HbA1c at Week 26 Comparing 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 HbA1c at Week 26 Comparing 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 | Baseline to Week 26 | An ANCOVA model was used for the analysis. |
| Change From Baseline in Body Weight at Week 26 | Baseline to Week 26 | An ANCOVA model was used for the analysis. |
| Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg | Baseline to Week 12 | An ANCOVA model was used for the analysis. |
| Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g) | Baseline to Week 26 | An ANCOVA model was used for analysis. No Measure of Dispersion was pre-specified to be calculated. |
| Percentage of Participants With HbA1c <6.5% at Week 26 | Week 26 | — |
| Percentage of Participants With HbA1c <7.0% at Week 26 | Week 26 | — |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | First dose of study drug to last dose of study drug (up to 56.3 weeks) + 4 weeks | An adverse event (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 the investigational medicinal product (IMP). |
| 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 56.3 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
Argentina, Brazil, Colombia, Germany, Hungary, Israel, Italy, Mexico, Poland, Romania, Russia, South Africa, Spain, Ukraine, United States
Participant flow
Recruitment details
Participants took part in the study at 106 investigative sites in United States, Argentina, Brazil, Colombia, Germany, Hungary, Israel, Italy, Mexico, Poland, Romania, Russian Federation, South Africa, Spain, Ukraine from 16 August 2017 to 11 December 2019.
Pre-assignment details
A total of 277 participants with a diagnosis of Type 2 Diabetes Mellitus were randomized 1:1:1 to 1 of the 3 treatment groups: Placebo, Sotagliflozin 200 milligram (mg) and Sotagliflozin 400 mg.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. | 93 |
| Sotagliflozin 200 mg Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. | 92 |
| Sotagliflozin 400 mg Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks. | 92 |
| Total | 277 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 7 | 6 |
| Overall Study | At the Participant's Own Request | 5 | 1 | 4 |
| Overall Study | Lost to Follow-up | 2 | 2 | 2 |
| Overall Study | Reason Not Specified | 3 | 4 | 1 |
| Overall Study | Study Terminated by Sponsor | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Sotagliflozin 200 mg | Sotagliflozin 400 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 68.0 years STANDARD_DEVIATION 8.3 | 66.8 years STANDARD_DEVIATION 10 | 67.3 years STANDARD_DEVIATION 9.6 | 67.4 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 41 Participants | 33 Participants | 33 Participants | 107 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 59 Participants | 59 Participants | 170 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hemoglobin A1c (HbA1c) | 8.38 percentage of HbA1c STANDARD_DEVIATION 1.06 | 8.28 percentage of HbA1c STANDARD_DEVIATION 1.03 | 8.25 percentage of HbA1c STANDARD_DEVIATION 0.87 | 8.30 percentage of HbA1c STANDARD_DEVIATION 0.99 |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants | 8 Participants | 7 Participants | 22 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 7 Participants | 3 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 76 Participants | 73 Participants | 78 Participants | 227 Participants |
| Region of Enrollment Argentina | 7 participants | 3 participants | 3 participants | 13 participants |
| Region of Enrollment Brazil | 9 participants | 7 participants | 8 participants | 24 participants |
| Region of Enrollment Colombia | 5 participants | 4 participants | 5 participants | 14 participants |
| Region of Enrollment Germany | 2 participants | 2 participants | 0 participants | 4 participants |
| Region of Enrollment Hungary | 1 participants | 3 participants | 0 participants | 4 participants |
| Region of Enrollment Israel | 7 participants | 2 participants | 8 participants | 17 participants |
| Region of Enrollment Italy | 5 participants | 2 participants | 4 participants | 11 participants |
| Region of Enrollment Mexico | 10 participants | 11 participants | 11 participants | 32 participants |
| Region of Enrollment Poland | 7 participants | 6 participants | 8 participants | 21 participants |
| Region of Enrollment Romania | 2 participants | 6 participants | 4 participants | 12 participants |
| Region of Enrollment Russia | 10 participants | 8 participants | 8 participants | 26 participants |
| Region of Enrollment South Africa | 3 participants | 2 participants | 4 participants | 9 participants |
| Region of Enrollment Spain | 7 participants | 10 participants | 11 participants | 28 participants |
| Region of Enrollment Ukraine | 2 participants | 8 participants | 4 participants | 14 participants |
| Region of Enrollment United States | 16 participants | 18 participants | 14 participants | 48 participants |
| Sex: Female, Male Female | 51 Participants | 48 Participants | 43 Participants | 142 Participants |
| Sex: Female, Male Male | 42 Participants | 44 Participants | 49 Participants | 135 Participants |
| Systolic Blood Pressure (SBP) | 144.72 millimeter of mercury (mmHg) STANDARD_DEVIATION 15.56 | 143.10 millimeter of mercury (mmHg) STANDARD_DEVIATION 14.98 | 144.20 millimeter of mercury (mmHg) STANDARD_DEVIATION 15.1 | 144.01 millimeter of mercury (mmHg) STANDARD_DEVIATION 15.17 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 93 | 6 / 94 | 3 / 90 |
| other Total, other adverse events | 44 / 93 | 44 / 94 | 29 / 90 |
| serious Total, serious adverse events | 21 / 93 | 18 / 94 | 20 / 90 |
Outcome results
Primary
Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo
An analysis of covariance (ANCOVA) model was used for the analysis.
Time frame: Baseline to Week 26
Population: Intent-to-treat (ITT) population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts \& washout imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo | -0.11 percentage of HbA1c | Standard Error 0.151 |
| Sotagliflozin 400 mg | Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo | -0.40 percentage of HbA1c | Standard Error 0.131 |
Comparison: The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) 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: 0.096295% CI: [-0.628, 0.051]ANCOVA
Secondary
Change From Baseline in Body Weight at Week 26
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Population: ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts \& washout imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at Week 26 | 0.39 kilogram (kg) | Standard Error 0.615 |
| Sotagliflozin 400 mg | Change From Baseline in Body Weight at Week 26 | -0.43 kilogram (kg) | Standard Error 0.48 |
| Sotagliflozin 400 mg | Change From Baseline in Body Weight at Week 26 | -1.02 kilogram (kg) | Standard Error 0.49 |
Comparison: The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline body weight as a covariate.p-value: 0.243295% CI: [-2.197, 0.557]ANCOVA
Comparison: The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline body weight as a covariate.p-value: 0.048795% CI: [-2.81, -0.008]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Population: ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts \& washout imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | 0.069 millimole per liter (mmol/L) | Standard Error 0.4482 |
| Sotagliflozin 400 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | -0.291 millimole per liter (mmol/L) | Standard Error 0.5056 |
| Sotagliflozin 400 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | -0.644 millimole per liter (mmol/L) | Standard Error 0.4348 |
Comparison: The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline FPG as a covariate.p-value: 0.550195% CI: [-1.5431, 0.822]ANCOVA
Comparison: The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline FPG as a covariate.p-value: 0.177995% CI: [-1.7524, 0.3246]ANCOVA
Secondary
Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Population: ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts \& washout imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo | -0.11 percentage of HbA1c | Standard Error 0.151 |
| Sotagliflozin 400 mg | Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo | -0.07 percentage of HbA1c | Standard Error 0.162 |
Comparison: The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) 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: 0.812495% CI: [-0.338, 0.431]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 control-based copy reference multiple imputation 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 | -2.50 mmHg | Standard Error 1.762 |
| Sotagliflozin 400 mg | Change From Baseline in SBP at Week 12 for All Participants | -5.74 mmHg | Standard Error 1.752 |
| Sotagliflozin 400 mg | Change From Baseline in SBP at Week 12 for All Participants | -7.86 mmHg | Standard Error 1.794 |
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 screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.123295% CI: [-7.365, 0.881]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 screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.009895% CI: [-9.433, -1.292]ANCOVA
Secondary
Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 12
Population: Analysis population included all 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 control-based copy reference multiple imputation under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg | -2.70 mmHg | Standard Error 1.815 |
| Sotagliflozin 400 mg | Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg | -4.84 mmHg | Standard Error 1.882 |
| Sotagliflozin 400 mg | Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg | -7.10 mmHg | Standard Error 1.842 |
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 screening, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.395495% CI: [-7.066, 2.792]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 screening, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.071695% CI: [-9.185, 0.386]ANCOVA
Secondary
Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g)
An ANCOVA model was used for analysis. No Measure of Dispersion was pre-specified to be calculated.
Time frame: Baseline to Week 26
Population: Analysis population included all participants with baseline UACR \> 30 mg/g in ITT population where, ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts \& washout imputation method.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g) | -4.56 percent change |
| Sotagliflozin 400 mg | Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g) | -26.99 percent change |
| Sotagliflozin 400 mg | Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g) | -30.66 percent change |
Comparison: The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and log-transformed baseline UACR as a covariate.p-value: 0.22295% CI: [-44.75, 14.77]ANCOVA
Comparison: The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of mean SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and log-transformed baseline UACR as a covariate.p-value: 0.196595% CI: [-45.05, 13.1]ANCOVA
Secondary
Percentage of Participants With HbA1c <6.5% at Week 26
Time frame: Week 26
Population: ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With HbA1c <6.5% at Week 26 | 2.2 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With HbA1c <6.5% at Week 26 | 5.4 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With HbA1c <6.5% at Week 26 | 8.7 percentage of participants |
Comparison: Percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of metformin use at screening (Yes, No), and the randomization strata of mean SBP (\<130, ≥130 mmHg) at screening.p-value: 0.24295% CI: [-2.17, 8.66]Cochran-Mantel-Haenszel
Comparison: Percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of metformin use at screening (Yes, No), and the randomization strata of mean SBP (\<130, ≥130 mmHg) at screening.p-value: 0.051395% CI: [0.04, 12.93]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HbA1c <7.0% at Week 26
Time frame: Week 26
Population: ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With HbA1c <7.0% at Week 26 | 4.3 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With HbA1c <7.0% at Week 26 | 16.3 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With HbA1c <7.0% at Week 26 | 17.4 percentage of participants |
Comparison: Percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of metformin use at screening (Yes, No), and the randomization strata of mean SBP (\<130, ≥130 mmHg) at screening.p-value: 0.006695% CI: [3.48, 20.61]Cochran-Mantel-Haenszel
Comparison: Percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of metformin use at screening (Yes, No), and the randomization strata of mean SBP (\<130, ≥130 mmHg) at screening.p-value: 0.004395% CI: [4.28, 21.75]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (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 the investigational medicinal product (IMP).
Time frame: First dose of study drug to last dose of study drug (up to 56.3 weeks) + 4 weeks
Population: Safety population included all randomized participants who received at least one dose of double-blind IMP. Two participants were randomized to Sotagliflozin 400 mg and dosed with Sotagliflozin 200 mg and 400 mg treatments during the study. Data for these participants were summarized in the Sotagliflozin 200 mg arm in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 82.8 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 86.2 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | 81.1 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 56.3 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 | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Hypoglycemic Events | Severe or documented symptomatic hypoglycemia | 35.5 percentage of participants |
| Placebo | Percentage of Participants With Hypoglycemic Events | Documented symptomatic hypoglycemia | 35.5 percentage of participants |
| Placebo | Percentage of Participants With Hypoglycemic Events | Any hypoglycemia | 40.9 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Documented symptomatic hypoglycemia | 28.7 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Any hypoglycemia | 40.4 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Severe or documented symptomatic hypoglycemia | 30.9 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Any hypoglycemia | 38.9 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Severe or documented symptomatic hypoglycemia | 27.8 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Documented symptomatic hypoglycemia | 27.8 percentage of participants |