Comparison of Pharmacodynamic Effects of Sotagliflozin and Empagliflozin in T2DM Patients With Mild to Moderate Hypertension

NCT03462069 | Completed Phase 2

• 3 other identifiers: PDY150102017-002309-36U1111-1186-2962
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To compare the metabolic and gastrointestinal pharmacodynamic (PD) effects of an 8 weeks treatment with sotagliflozin once daily (QD) to an 8 weeks treatment to empagliflozin QD in mild or moderate hypertensive T2DM patients on a stable treatment regimen with metformin and an angiotensin converting enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB) under standardized diet conditions. Secondary Objectives:

• To compare the renal and cardiovascular PD effects of an 8 weeks treatment with sotagliflozin QD to an 8 weeks treatment to empagliflozin QD in mild or moderate hypertensive T2DM patients on a stable treatment regimen with metformin and an ACE inhibitor or ARB.
• To evaluate the safety and tolerability of an 8 weeks QD treatment with sotagliflozin or empagliflozin in mild to moderate hypertensive T2DM patients on a stable treatment with metformin and an ACE inhibitor or ARB.
• To evaluate the pharmacokinetic (PK) profile of sotagliflozin in steady state conditions.

Conditions

Diabetes Mellitus

Outcome Measures

Primary Outcomes (7)

• Assessment of pharmacodynamic (PD) parameters in feces

  Change from baseline in fecal sodium excretion

  Baseline and on Day 55 and 56 (over 48 hours)

• Assessment of pharmacodynamic (PD) parameters in feces

  Change from baseline in fecal short-chain fatty acids (SCFA)

  Baseline and on Day 55 and 56 (over 48 hours)

• Assessment of pharmacodynamic (PD) parameters in feces

  Change from baseline in fecal pH

  Baseline and on Day 55 and 56 (over 48 hours)

• Assessment of PD parameters in urine

  Change from baseline in 24-hour urinary glucose excretion

  Baseline and on Day 56 (over 24 hours)

• Assessment of PD parameters in urine

  Change from baseline in 24-hour sodium excretion

  Baseline and on Day 56 (over 24 hours)

• Assessment of PD parameters in blood

  14 hour plasma glucose profile after standardized meals

  Baseline and on Day 56

• Assessment of PD parameters in blood

  14 hour plasma glucagon-like peptide 1 (GLP-1) profile after standardized meals

  Baseline and on Day 56

Secondary Outcomes (13)

• Fasting metabolic laboratory panel

  Baseline and on Day 56

• Ambulatory Blood Pressure Measurement (ABPM)

  Baseline and on days 54 until Day 56

• Cardiovascular parameters

  Baseline and on Day 56

• Pulse wave velocity

  Baseline and on Day 55

• Continuous Glucose Monitoring (CGM)

  Baseline, last 3 days of treatment

Study Arms (2)

Treatment A (Test)

EXPERIMENTAL

Sotagliflozin 2 tablets administered once daily with 1 empagliflozin placebo capsule prior to the first meal of the day

Drug: Sotagliflozin (SAR439954); Drug: Placebo

Treatment B (Reference)

ACTIVE COMPARATOR

Empagliflozin 1 capsule administered once daily with 2 sotagliflozin placebo tablets prior to the first meal of the day

Drug: Placebo; Drug: Empagliflozin

Interventions

Sotagliflozin (SAR439954) DRUG

Pharmaceutical form: tablet Route of administration: oral

Treatment A (Test)

Placebo DRUG

Pharmaceutical form: tablet Route of administration: oral

Treatment B (Reference)

Empagliflozin DRUG

Pharmaceutical form: capsule Route of administration: oral

Also known as: Jardiance®

Treatment B (Reference)

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients with Type 2 Diabetes Mellitus (T2DM) (diagnosed at least 1 year before screening visit), between 18 and 74 years of age, inclusive, with:
• Glycated Haemoglobin A1c (HbA1c) at screening between 6.5% and 11%.
• On a stable treatment with metformin, i.e., no change in dose regimen or in dose levels in the last 3 months prior to screening and throughout the study.
• On a stable treatment with an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker, i.e., no change in dose regimen or in dose levels in the last 4 weeks prior to screening and until randomization.
• On a stable treatment with an ACE inhibitor or an angiotensin receptor blocker after switching from beta-blockers and/or thiazides for eligible patients after screening, i.e., no change in dose regimen and in dose levels in the last 4 weeks prior to run-in phase and until randomization
• Body weight between 50.0 kg and 130 kg, inclusive, if male, and between 40.0 kg and 110 kg, inclusive, if female, body mass index between 18.0 and 38.0 kg/m2, inclusive.
• Kidney function: Estimated glomerular filtration rate at screening must be 60 mL/min/1.73m2 or higher.

You may not qualify if:

• Patients with severe anemia, severe cardiovascular, gastrointestinal, respiratory, neurological, osteomuscular, psychiatric, or active malignant tumor or other major systemic disease or patients with infectious disease, signs of acute illness, or short life expectancy making implementation of the protocol or interpretation of the study results difficult (as evaluated by detailed medical history and complete physical and laboratory examination).
• Heart failure New York Heart Association (NYHA) Classification III/IV.
• Any clinically significant abnormality in echocardiography performed at screening as judged by the investigator based on age, gender and medical history of the individual patient.
• History of myocardial infarction within the last 12 months prior to screening.
• Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol (e.g., long-term systemic glucocorticoids) and refusing or unable to take alternative treatment.
• Type 1 diabetes mellitus.
• Secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
• Clinically significant pulmonary hypertension, in particular World Health Organisation (WHO) Classes IV (Pulmonary hypertension due to chronic thrombotic and/or embolic disease \[CTEPH\]) and V (miscellaneous).
• Diabetic retinopathy.
• History of diabetic ketoacidosis or non-ketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
• History of severe hypoglycemia resulting in hospitalization or unconsciousness/seizures within 6 months prior to the Screening visit.
• History of prior gastric or intestinal surgical procedure including gastric banding within 3 years before the Screening Visit. Any gastrointestinal surgery with removal of part of the bowels or the stomach
• History of unexplained pancreatitis, chronic pancreatitis, stomach/gastric surgery, inflammatory bowel disease.
• Known hypersensitivity to sotagliflozin, empagliflozin or any excipient of the drug products.
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Investigational Site Number 2760001

Berlin, 10117, Germany

Location

Related Publications (1)

• Posch MG, Walther N, Ferrannini E, Powell DR, Banks P, Wason S, Dahmen R. Metabolic, Intestinal, and Cardiovascular Effects of Sotagliflozin Compared With Empagliflozin in Patients With Type 2 Diabetes: A Randomized, Double-Blind Study. Diabetes Care. 2022 Sep 1;45(9):2118-2126. doi: 10.2337/dc21-2166.

  PMID: 35817022 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol; empagliflozin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2018
• First Posted: March 12, 2018
• Study Start: March 12, 2018
• Primary Completion: April 18, 2019
• Study Completion: April 18, 2019
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)