Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as [14C]-LX4211, LX4211 Low Dose, Sotagliflozin
LX4211 · 25 trials · 13 indications
Beta hydroxybutyrate (BHB) time \> 0.6 millimole per liter (mmol/L) as measured by the DGK during the 200mg dosing period in the MDI vs. HCL groups.
Beta hydroxybutyrate (BHB) time \> 0.6 mmol/L as measured by the DGK during the 400mg dosing period in the MDI vs. HCL groups.
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 the analysis.
An Analysis of covariance (ANCOVA) model was used for 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.
To assess 24-hour urinary glucose excretion, urine was collected over a 24-hour period and evaluated for glucose concentration.
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.
Measured from blood samples
| Arm | Type | Description |
|---|---|---|
| Treatment Group A | EXPERIMENTAL | 200mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 400mg sotagliflozin for 6 weeks |
| Treatment Group B | EXPERIMENTAL | 400mg sotagliflozin for 6 weeks, washout for 2 weeks, then receive 200mg sotagliflozin for 6 weeks |
| 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. |
| Treatment A | EXPERIMENTAL | - |
| Treatment B | EXPERIMENTAL | - |
| Treatment C | EXPERIMENTAL | - |
| Treatment D | EXPERIMENTAL | - |
| Low Dose | EXPERIMENTAL | A low dose of LX4211; daily oral intake for 28 days |
| High Dose | EXPERIMENTAL | A high dose of LX4211; daily oral intake for 28 days |
| 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). |
| LX4211 Placebo | PLACEBO_COMPARATOR | - |
| Solid Oral Dose - 150 mg tablets | EXPERIMENTAL | - |
| Solid Oral Dose - 50 mg tablets | EXPERIMENTAL | - |
| Liquid Oral Dose | EXPERIMENTAL | - |
| Platelet function in healthy subjects administered sotagliflozin vs. antiplatelet agents | EXPERIMENTAL | Platelet responsiveness will be assessed in the blood from subjects administered sotagliflozin, aspirin, clopidogrel, or apixaban in randomized order given as a single drug administration. |
| Name | Type | Description |
|---|---|---|
| Sotagliflozin Low Dose | DRUG | 200 mg Sotagliflozin, once daily for 6 weeks |
| Sotagliflozin High Dose | DRUG | 400 mg Sotagliflozin, once daily for 6 weeks |
| Dual Continuous Glucose and Ketone Monitor | DEVICE | Abbott Libre X dual continuous glucose and ketone monitor (DGK) device. |
| 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 |
| 75 mg LX4211 | DRUG | Subjects will receive 75 mg LX4211 once daily |
| 200 mg LX4211 | DRUG | Subjects will receive 200 mg LX4211 once daily. |
| 400 mg LX4211 | DRUG | Subjects will receive 400 mg LX4211 once daily. |
| LX4211 Low Dose | DRUG | A low dose of LX4211; daily oral intake for 28 days |
| LX4211 High Dose | DRUG | A high dose of LX4211; daily oral intake for 28 days |
| Volagidemab | DRUG | Volagidemab is a human monoclonal antibody glucagon receptor antagonist (GRA). |
| LX4211 | DRUG | Subjects will receive LX4211 once daily for 7 days |
| LX4211 Placebo | DRUG | Subjects will receive LX4211 placebo once daily for 7 days |
| Januvia® | DRUG | 100 mg Januvia® (sitagliptin) administered as one 100 mg sitagliptin tablet |
| 1000 mg metformin | DRUG | 1000 mg metformin given as a solid oral dose form |
| 300 mg LX4211 (150 mg tablets) | DRUG | Single oral dose of two 150 mg tablets LX4211 |
| 300 mg LX4211 (50 mg tablets) | DRUG | Single oral dose of six 50 mg tablets LX4211 |
| 300 mg LX4211 (liquid) | DRUG | Single 30 mL dose of liquid oral solution LX4211 (10 mg/mL) |
| Sotagliflozin (SOTA) followed by 3 drugs in a random order | DRUG | 400 mg/day SOTA Each drug will be given daily for 2 weeks. |
| Aspirin followed by 3 drugs in a random order | DRUG | 81 mg/day Aspirin Each drug will be given daily for 2 weeks. |
| Clopidogrel followed by 3 drugs in a random order | DRUG | 75 mg/day clopidogrel Each drug will be given daily for 2 weeks. |
| Eliquis followed by 3 drugs in a random order | DRUG | 5 mg orally twice daily Eliquis Each drug will be given daily for 2 weeks. |
Inclusion Criteria: 1. All individuals between the ages of \>18 years old, inclusive, at the time of screening; 2. Individuals able to become pregnant must: 1. be ≥1 year post-menopausal or documented as being surgically sterile, or 2. agree to use two methods of contraception during the ent...
LX4211 is an investigational oral small molecule developed for the treatment of type 2 diabetes mellitus. It has been studied both as monotherapy and in combination with metformin in patients with inadequate glycemic control, and in patients with type 2 diabetes and renal impairment. It is not approved and remains in clinical development.
LX4211 is being developed by Lexicon Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker LXRX. Lexicon sponsored the clinical program evaluating LX4211 in type 2 diabetes mellitus, including Phase 1 drug interaction studies and a Phase 2 study of LX4211 added to metformin.
LX4211 is in Phase 2 clinical development for type 2 diabetes mellitus. Six trials have been completed, including a Phase 2 study of LX4211 with metformin in 299 patients and several Phase 1 studies, and no trials are currently active. It is investigational and has not been approved by the FDA.
Six completed trials have evaluated LX4211. The Phase 2 study NCT01376557 tested LX4211 with metformin in 299 patients with inadequate glycemic control. Phase 1 studies include NCT01555008 in type 2 diabetes with renal impairment, NCT01441232 with Januvia, and NCT01292993 evaluating the LX4211 and metformin interaction in healthy subjects.
Across the six completed LX4211 trials, 417 patients have been enrolled in total. The largest was the Phase 2 study NCT01376557 with 299 patients, followed by the Phase 1 renal impairment study NCT01555008 with 31 patients. The trials were randomized, double blind, and controlled.