E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the superiority of sotagliflozin dose 1 versus placebo with respect to HbA1c (glycosylated hemoglobin) reduction in patients with T2D (type 2 diabetes mellitus) who have inadequate glycemic control on basal insulin alone or with OADs (oral antidiabetic drugs). |
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E.2.2 | Secondary objectives of the trial |
To assess the effects of sotagliflozin dose 1 versus placebo on Fasting Plasma Glucose (FPG), Systolic Blood Pressure (SBP), and body weight
To assess the effects of sotagliflozin dose 2 versus placebo on hemoglobin A1c, body weight, SBP, and FPG
To assess the effects of sotagliflozin dose 1 versus placebo on the proportion of patients with HbA1c <7.0% or HbA1c <6.5%
To assess the effects of sotagliflozin dose 2 versus placebo on the proportion of patients with HbA1c <7.0% or HbA1c <6.5%
To evaluate the safety of sotagliflozin doses 1 and 2 versus placebo |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
CGM (continuous glucose monitoring) substudy
To compare the effect of sotagliflozin dose 1versus placebo on the percentage of time spent within the range of 70-180 mg/dL (3.9 -10 mmol/L) over 24 hours
(Please refer to the protocol EFC14868) |
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E.3 | Principal inclusion criteria |
- Patients with T2D (Type 2 diabetes) using any types of basal insulin alone or in combination with up to 2 OADs (oral antidiabetic drugs)
- Patient has given written informed consent to participate in the study in accordance with local regulations |
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E.4 | Principal 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 (eg, insulin glargine, Neutral Protamine
Hagedorn [NPH], detemir, or degludec) for less than 6 months before
Screening
- Dose of basal insulin (eg, insulin glargine, NPH, detemir, or degludec)
not stable for 8 weeks before Screening (ie, 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 (eg, insulin
glargine, NPH, detemir, or degludec), ie, prandial or rapid-acting
insulins, short-acting insulins, GLP -1 receptor agonists, or inhaled
prandial insulin (Afrezza) within 8 weeks of Screening
- Use of a selective SGLT2 inhibitor (eg, canagliflozin, dapagliflozin, or
empagliflozin) within 12 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
- Patients 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 (eg, genetic Hb variants) compromising the reliability of
HbA1c assessment or medical conditions that affect interpretation of
HbA1c results (eg, blood transfusion or severe blood loss in the last 3
months prior to randomization, any condition that shortens erythrocyte
survival)
- Patient 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
- Patients unwilling to perform SMBG (self monitoring of blood glucose),
complete the patient diary or comply with study visits and other study
procedures as required per protocol
- Hemoglobin A1c (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 BP measurements >180 mmHg (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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change from baseline in hemoglobin A1c (HbA1c )(for sotagliflozin dose 1) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1- Absolute change from baseline in FPG (for sotagliflozin dose 1)
2- Absolute change from baseline in SBP for patients with baseline SBP≥
130 mmHg (for sotagliflozin dose 1)
3- Absolute change from baseline in SBP for all patients (for sotagliflozin
dose 1)
4- Absolute change from baseline in BW (for sotagliflozin dose 1)
5- Percentage of patients with HbA1c <7.0% (for sotagliflozin dose 1)
6- Percentage of patients with HbA1c <6.5% (for sotagliflozin dose 1)
7- Absolute change from baseline in HbA1c (for sotagliflozin dose 2)
8- Absolute change from Baseline in FPG (for sotagliflozin dose 2)
9- Change in SBP for patients with baseline ≥130 mmHg (for
sotagliflozin dose 2)
10- Absolute change from baseline in BW (for sotagliflozin dose 2)
11- Percentage of patients with HbA1c <7.0% (for sotagliflozin dose 2)
12- Percentage of patients with HbA1c <6.5% (for sotagliflozin dose 2)
13- Proportion of patients with adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4-5-6-7-8-10-11-12- Baseline to week 18
2-3-9- Baseline to week 12
13- Up to week 54 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient Reported outcomes |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Canada |
Czechia |
France |
Hungary |
Slovakia |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last Subject Last Visist (LSLV) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |