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 |
High sugar levels in the blood |
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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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 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 400 mg versus placebo in the proportion of patients with glycosylated A1C <7.0% at Week 24 and no episode of severe hypoglycemia and no episode of diabetic ketoacidosis (DKA) after randomization. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the change from Baseline of sotagliflozin versus placebo in hierarchical order on the following:
• A1C
• Body weight
• Systolic blood pressure (SBP)
• Bolus insulin dose |
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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 |
Objective: To evaluate satiety (appetite) in a subset of enrolled patients.
The instrument used will be the Patient Satiety Daily Diary (PSDD). Up to 280 patients (140 per treatment group) will be recruited for this substudy.
The patients will be instructed to complete the paper diary each day, before the first meal of the day for the last 2 weeks of the double-blind Treatment Period (ie, during Week 23 and during Week 24, a total of 14 days). The diaries will be returned to the site at the visit scheduled for the end of Week 24. |
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E.3 | Principal inclusion criteria |
1) Patient has given written informed consent to participate in the study in accordance with local regulations
2) Adult patients 18 years and older with a diagnosis of T1D made at least 1 year prior to informed consent
3) Patients are being treated with insulin(s) or insulin analog(s)
4) Non-fast acting insulin dose is stable (±20%) for 2 weeks prior to the Screening Visit
5) At the Screening Visit, A1C must be between 7.0% and 11.0%, inclusive
6) BMI ≥18.5 kg/m2
7) Must be willing and able to perform SMBG and complete the study diary as required per protocol
8) Females of childbearing potential must use an adequate method of contraception to avoid pregnancy throughout the duration of the study and for 30 days after the last dose of study drug. Females of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Postmenopause is defined as no menses for ≥12 months without another cause. For females with questionable menopausal history (eg, irregular menstrual periods and age >40 years) a documented serum follicle-stimulating hormone (FSH) level must be ≥30 mIU/mL.
9) Females of childbearing potential must have a negative serum or urine pregnancy test prior to the start of study drug. In the case of positive urine pregnancy testing, a negative serum sample for pregnancy testing, to confirm that the patient is not pregnant, must be obtained prior to start of study. |
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E.4 | Principal exclusion criteria |
1) Therapies and/or medications:
a) Use of antidiabetic agent other than insulin(s) or insulin analog(s) at the time of screening (any medication other than insulin or insulin analog used for treatment of T1D must be washed out for at least 8 weeks prior to the Screening Visit)
b) Any prior exposure to sotagliflozin
c) Use of SGLT inhibitors within 8 weeks prior to Screening.
d) Chronic systemic corticosteroid use, defined as any dose of systemic corticosteroid taken for more than 4 consecutive weeks within the 6 months prior to the Screening Visit.
2) Diabetes-related conditions:
a) Type 2 diabetes mellitus, or severely uncontrolled T1D as determined by the Investigator
b) History of severe hypoglycemic event within 1 month prior to the Screening Visitc) History of DKA or nonketotic hyperosmolar state within 1 month of Screening OR ≥2 episodes of DKA or nonketotic hyperosmolar state within 6 months of Screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) To demonstrate the superiority of sotagliflozin 400 mg versus placebo in the proportion of patients with A1C <7.0% at Week 24 and no episode of severe hypoglycemia and no episode of DKA after randomization when used as an adjunct in normal weight and overweight/obese adult patients with T1D who have inadequate glycemic control with insulin therapy. |
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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) |
To be measured as change from Baseline in sotagliflozin 400 mg compared to placebo for each of the following:
2) A1C at Week 24
3) Body weight at Week 24 (absolute and percent change)
4) SBP at Week 16 in the subset of patients with Baseline SBP ≥130 mm Hg
5) Bolus insulin dose at Week 24 (as an average over the 3-5 days prior to the visit) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2) At week 24
3) At week 24
4) At week 16
5) At week 24 |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Colombia |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Italy |
New Zealand |
Peru |
Poland |
Slovakia |
South Africa |
Spain |
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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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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |