Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Sotagliflozin · 19 trials · 13 indications
KCCQ is a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores are generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. Higher scores reflect better health status.
An analysis of covariance (ANCOVA) model was used for the analysis.
An analysis of covariance (ANCOVA) model was used for the analysis.
An analysis of covariance (ANCOVA) model was used for the analysis.
An Analysis of covariance (ANCOVA) model was used for analysis.
An analysis of covariance (ANCOVA) model was used for the analysis.
Missing data are imputed using the retrieved dropouts imputation method. An analysis of covariance (ANCOVA) model was used for the analysis.
An analysis of covariance (ANCOVA) model was used for the analysis.
The primary composite endpoint included blood samples for the assessment of Hemoglobin A1C to determine the participants with a value \<7.0%. A central blinded adjudication process determined whether participants experienced either DKA or Severe Hypoglycemia.
Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. Least square (LS) means were obtained from a mixed-effects model for repeated measures (MMRM) that included fixed, categorical effects of treatment, randomization strata of insulin delivery method (MDI, CSII), randomization strata of Week -2 A1C (\<= 8.5%, \>8.5%), time (study week), a treatment-by-time interaction, and baseline A1C-by-time interaction as a covariate. A negative change from baseline (a reduction of A1C value at Week 24) indicates an improvement.
To investigate the effect of sotagliflozin 200mg once daily in addition to standard of care on quality of life (QoL). KCCQ clinical summary score (no unit, ranges from 0 to 100 with higher scores reflecting better health status).
Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-baseline Least Square (LS) mean values were obtained from mixed-effects model repeated measures (MMRM) model with treatment, randomization strata of insulin delivery method (continuous subcutaneous insulin infusion \[CSII\] or multiple daily injection \[MDI\]), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline A1C-by-time interaction as a covariate.
Baseline was calculated as the mean value from Day -6 to -2 for Expansion groups and from Day -6 to Day -3 for Pioneer Group. Percent mean change from baseline was calculated as 100\*(sum \[each daily value - baseline\]/number of assessments)/baseline over Days 3 to 27. Least squares (LS) Means and confidence interval (CI) for the Expansion groups were based on an analysis of covariance (ANCOVA) model with covariates of baseline mean total bolus insulin, treatment group, factor used to stratify the randomization (screening A1C \<= 8%, \> 8%), and random effect of participant\*treatment group. LS Means and CI for the Pioneer Group were based on the arithmetic treatment mean.
Quantify the effects of combination adjunctive therapy on glycemic control. Though it has limitations, the HbA1c remains the gold standard measurement of glycemic control in diabetes.
| Arm | Type | Description |
|---|---|---|
| Sotagliflozin | EXPERIMENTAL | Following an up to 3-week screening period, sotagliflozin 400 milligrams (mg) tablets will be administered as two 200 mg tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 26 weeks. |
| Placebo | PLACEBO_COMPARATOR | Following an up to 3-week screening period, sotagliflozin-matching placebo 400 mg tablets will be administered as two 200 mg tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 26 weeks. |
| Sotagliflozin 400 mg | EXPERIMENTAL | Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks. |
| Sotagliflozin 200 mg | EXPERIMENTAL | Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks. |
| Glimepiride | ACTIVE_COMPARATOR | Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks. |
| Empagliflozin 25 mg | ACTIVE_COMPARATOR | Following a 2-week run-in period, placebo matching sotagliflozin administered as two tablets (identical to sotagliflozin in appearance) and one capsule of empagliflozin 25 mg, once daily before the first meal of the day for up to 26 weeks. |
| Sotagliflozin 400 mg + Metformin | EXPERIMENTAL | Following a 2-week run-in period, sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks. |
| Placebo + Metformin | PLACEBO_COMPARATOR | Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks. |
| Sotagliflozin 200 milligrams (mg) | EXPERIMENTAL | Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), orally, for 24 weeks followed by a 28 week extension period. |
| Sotagliflozin 75 mg | EXPERIMENTAL | Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally for 12 weeks. |
| Sotagliflozin 400 mg - Pioneer Group | EXPERIMENTAL | Sotagliflozin 400 milligram (mg) (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration. |
| Placebo - Expansion Group | PLACEBO_COMPARATOR | Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration. |
| Sotagliflozin 400 mg - Expansion Group | EXPERIMENTAL | Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration. |
| volagidemab 35 mg | ACTIVE_COMPARATOR | Each participant will receive 12-week insulin-adjunctive treatment with both: (1) SGLTi (sotagliflozin 200 mg PO each day) + Placebo and (2) SGLTi + GRA (volagidemab 35 mg subcutaneously each week), in a random-order, cross-over design with a 14-week washout period between treatment periods. Volagidemab is a human monoclonal antibody glucagon receptor antagonist (GRA). |
| Group 1 | EXPERIMENTAL | Subjects with normal renal function |
| Group 2 | EXPERIMENTAL | Subjects with mild renal impairment |
| Group 3 | EXPERIMENTAL | Subjects with moderate renal impairment |
| Group 4 | EXPERIMENTAL | Subjects with severe renal impairment |
| Group 5 | EXPERIMENTAL | Subjects with ESRD requiring HD |
| Name | Type | Description |
|---|---|---|
| Sotagliflozin | DRUG | Sotagliflozin will be administered as a tablet(s), orally once daily. |
| Placebo | DRUG | Placebo will be administered as a tablet(s) (identical to the sotagliflozin tablet in appearance), orally once daily. |
| Sotagliflozin (SAR439954) | DRUG | Pharmaceutical form: tablet Route of administration: oral |
| Glimepiride | DRUG | Pharmaceutical form: capsule Route of administration: oral |
| Metformin | DRUG | Pharmaceutical form: tablet Route of administration: oral |
| Empagliflozin | DRUG | Empagliflozin 25 mg capsule was administered, once daily before the first meal of the day. |
| Insulin glargine (HOE901) | DRUG | Pharmaceutical form: Solution Route of administration: Subcutaneous |
| Oral Antidiabetes Drugs (OADs) | DRUG | OADs (including metformin) as prescribed by the investigator as per local labeling. |
| Sulfonylurea | DRUG | Pharmaceutical form: tablet Route of administration: oral |
| Volagidemab | DRUG | Volagidemab is a human monoclonal antibody glucagon receptor antagonist (GRA). |
Inclusion Criteria: * KCCQ CSS \< 85. * NYHA functional class II or III * A diagnosis of HCM consistent with the current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guideline definition: unexplained left ventricular (LV) hypertrophy with n...