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

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ClinicalTrials.gov Identifier: NCT03462069
Recruitment Status : Recruiting
First Posted : March 12, 2018
Last Update Posted : October 24, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus Drug: Sotagliflozin (SAR439954) Drug: Placebo Drug: Empagliflozin Phase 2

Detailed Description:
The total study duration per patient is 70-105 days (for patients without drug washout/switch period), and up to 175 days (for patients with drug washout/switch period), including 2-30 days of screening, 5 days of run-in period, 56 days of treatment period, and a 7-14 days of follow-up period.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel-group, 2-treatment Multiple Dose Study to Assess the Intestinal, Metabolic and Cardiovascular Effects of an 8 Weeks Treatment With Sotagliflozin QD as Compared With Empagliflozin Once a Day (QD) in Type 2 Diabetes Mellitus (T2DM) Patients With Mild to Moderate Hypertension
Actual Study Start Date : March 12, 2018
Estimated Primary Completion Date : August 7, 2019
Estimated Study Completion Date : August 7, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment A (Test)
Sotagliflozin 2 tablets administered once daily with 1 empagliflozin placebo capsule prior to the first meal of the day
Drug: Sotagliflozin (SAR439954)

Pharmaceutical form: tablet

Route of administration: oral


Drug: Placebo

Pharmaceutical form: capsule

Route of administration: oral


Active Comparator: Treatment B (Reference)
Empagliflozin 1 capsule administered once daily with 2 sotagliflozin placebo tablets prior to the first meal of the day
Drug: Placebo

Pharmaceutical form: tablet

Route of administration: oral


Drug: Empagliflozin

Pharmaceutical form: capsule

Route of administration: oral

Other Name: Jardiance®




Primary Outcome Measures :
  1. Assessment of pharmacodynamic (PD) parameters in feces [ Time Frame: Baseline and on Day 55 and 56 (over 48 hours) ]
    Change from baseline in fecal sodium excretion

  2. Assessment of pharmacodynamic (PD) parameters in feces [ Time Frame: Baseline and on Day 55 and 56 (over 48 hours) ]
    Change from baseline in fecal short-chain fatty acids (SCFA)

  3. Assessment of pharmacodynamic (PD) parameters in feces [ Time Frame: Baseline and on Day 55 and 56 (over 48 hours) ]
    Change from baseline in fecal pH

  4. Assessment of PD parameters in urine [ Time Frame: Baseline and on Day 56 (over 24 hours) ]
    Change from baseline in 24-hour urinary glucose excretion

  5. Assessment of PD parameters in urine [ Time Frame: Baseline and on Day 56 (over 24 hours) ]
    Change from baseline in 24-hour sodium excretion

  6. Assessment of PD parameters in blood [ Time Frame: Baseline and on Day 56 ]
    14 hour plasma glucose profile after standardized meals

  7. Assessment of PD parameters in blood [ Time Frame: Baseline and on Day 56 ]
    14 hour plasma glucagon-like peptide 1 (GLP-1) profile after standardized meals


Secondary Outcome Measures :
  1. Fasting metabolic laboratory panel [ Time Frame: Baseline and on Day 56 ]
    Change from baseline in fasting plasma glucose

  2. Ambulatory Blood Pressure Measurement (ABPM) [ Time Frame: Baseline and on days 54 until Day 56 ]
    Change from baseline in average 24h systolic arterial pressure

  3. Cardiovascular parameters [ Time Frame: Baseline and on Day 56 ]
    Change from baseline in plasma aldosterone

  4. Pulse wave velocity [ Time Frame: Baseline and on Day 55 ]
    Change from baseline in carotid-femoral pulse wave velocity

  5. Continuous Glucose Monitoring (CGM) [ Time Frame: Baseline, last 3 days of treatment ]
    Change from baseline in average diurnal glucose

  6. Echocardiography [ Time Frame: Baseline and on Day 54 ]
    Change from baseline in left ventricular ejection fraction (LVEF)

  7. Echocardiography [ Time Frame: Baseline and on Day 54 ]
    Change from baseline in left ventricular end-diastolic diameter

  8. Plasma Volume Measurement [ Time Frame: Baseline and on Day 54 ]
    Change from baseline in plasma volume

  9. Adverse events [ Time Frame: Over 15 weeks ]
    Number of patients with reported adverse events

  10. Assessment of pharmacokinetic (PK) parameters: Cmax [ Time Frame: 24 hours after last investigational medicinal product (IMP) administration ]
    Sotagliflozin: maximum plasma concentration observed (Cmax)

  11. Assessment of pharmacokinetic (PK) parameters: Ctrough [ Time Frame: 24 hours after last IMP administration ]
    Sotagliflozin: plasma concentration observed before administration during repeated dosing (Ctrough)

  12. Assessment of pharmacokinetic (PK) parameters: AUCtau [ Time Frame: 24 hours after last IMP administration ]
    Sotagliflozin: Area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval (AUCtau)

  13. Assessment of pharmacokinetic (PK) parameters: tmax [ Time Frame: 24 hours after last IMP administration ]
    Sotagliflozin: First time to reach Cmax (tmax)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • 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:

    • Hypertension grades 1 or 2 as defined by the European Society of Hypertension (ESH)/European Society of Cardiology (ESC) at screening; systolic blood pressure (SBP) has to be in the range of 140-179 mmHg (after 10 minutes resting in supine position, measurement in triplicate with each measurement to be within this range at screening). If the blood pressure (BP) range is not met at screening, one repeat measurement at another occasion is allowed prior to inclusion into the study.
    • 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.

Exclusion criteria:

  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03462069


Contacts
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-Us@sanofi.com

Locations
Germany
Investigational Site Number 2760001 Recruiting
Berlin, Germany, 13353
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03462069     History of Changes
Other Study ID Numbers: PDY15010
2017‐002309‐36 ( EudraCT Number )
U1111-1186-2962 ( Other Identifier: UTN )
First Posted: March 12, 2018    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Diabetes Mellitus
Hypertension
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Diseases
Cardiovascular Diseases
Empagliflozin
Hypoglycemic Agents
Physiological Effects of Drugs