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Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking Insulin Alone or With Other Oral Antidiabetic Agents (SOTA-INS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03285594
Recruitment Status : Completed
First Posted : September 18, 2017
Results First Posted : May 11, 2021
Last Update Posted : May 11, 2021
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Lexicon Pharmaceuticals

Brief Summary:

Primary Objective:

To demonstrate the superiority of sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1C (HbA1c) reduction in participants with type 2 diabetes mellitus (T2D) who have inadequate glycemic control on basal insulin alone or with oral antidiabetes drugs (OADs).

Secondary Objectives:

  • To assess the effects of sotagliflozin 400 mg versus placebo on fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), and HbA1c.
  • To assess the effects of sotagliflozin 200 mg versus placebo on HbA1c, body weight, FPG, and SBP.
  • To evaluate the safety of sotagliflozin 400 and 200 mg versus placebo.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Sotagliflozin Drug: Insulin glargine (HOE901) Drug: Placebo Drug: Oral Antidiabetes Drugs (OADs) Phase 3

Detailed Description:
Up to 60 weeks (Screening phase of up to 2 weeks, a 4-week Lantus titration/single-blind placebo Run-in phase), a 52-week double blind Treatment Period, and a 2-week post-treatment Follow-up Period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 571 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Basal Insulin Alone or in Addition to Oral Antidiabetes Drugs (OADs)
Actual Study Start Date : September 15, 2017
Actual Primary Completion Date : September 17, 2019
Actual Study Completion Date : September 27, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Following a 4-week run-in period, participants were randomized to matching placebo to sotagliflozin 200 milligrams (mg) administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Drug: Insulin glargine (HOE901)

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Other Name: Lantus

Drug: Placebo

Pharmaceutical form: Tablet

Route of administration: Oral


Drug: Oral Antidiabetes Drugs (OADs)
OADs (including metformin) as prescribed by the investigator as per local labeling.

Experimental: Sotagliflozin 200 mg
Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Drug: Sotagliflozin

Pharmaceutical form: Tablet

Route of administration: Oral

Other Name: SAR439954

Drug: Insulin glargine (HOE901)

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Other Name: Lantus

Drug: Placebo

Pharmaceutical form: Tablet

Route of administration: Oral


Drug: Oral Antidiabetes Drugs (OADs)
OADs (including metformin) as prescribed by the investigator as per local labeling.

Experimental: Sotagliflozin 400 mg
Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.
Drug: Sotagliflozin

Pharmaceutical form: Tablet

Route of administration: Oral

Other Name: SAR439954

Drug: Insulin glargine (HOE901)

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Other Name: Lantus

Drug: Oral Antidiabetes Drugs (OADs)
OADs (including metformin) as prescribed by the investigator as per local labeling.




Primary Outcome Measures :
  1. Change From Baseline in Hemoglobin A1c (HbA1c) at Week 18 [ Time Frame: Baseline and Week 18 ]
    An analysis of covariance (ANCOVA) model was used for the analysis.


Secondary Outcome Measures :
  1. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 [ Time Frame: Baseline and Week 18 ]
    FPG was performed in fasting state, that is, without any food intake (except for water) for at least 8 hours. An ANCOVA model was used for the analysis.

  2. Change From Baseline in Body Weight at Week 18 [ Time Frame: Baseline and Week 18 ]
    An ANCOVA model was used for the analysis.

  3. Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg at Week 12 [ Time Frame: Baseline and Week 12 ]
    An ANCOVA model was used for the analysis. Here, N is the number of participants with data available at a given time point.

  4. Change From Baseline in SBP at Week 12 for All Participants [ Time Frame: Baseline to Week 12 ]
    An ANCOVA model was used for the analysis.

  5. Change From Baseline in HbA1c at Week 52 [ Time Frame: Baseline and Week 52 ]
    An ANCOVA model was used for the analysis.

  6. Change From Baseline in Body Weight at Week 52 [ Time Frame: Baseline and Week 52 ]
    An ANCOVA model was used for the analysis.

  7. Percentage of Participants With Adverse Events (AEs) [ Time Frame: First dose of study drug to last dose of study drug (up to 55.7 weeks) + 2 weeks ]
    An AE is any untoward medical occurrence in a participants or clinical investigation participants administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.


Other Outcome Measures:
  1. Percentage of Participants With Hypoglycemic Events [ Time Frame: Up to 55.7 weeks ]
    Percentage of participants with hypoglycemic events are reported for the following 3 categories: Any hypoglycemia (as reported in the Electronic Case Report Form); Documented symptomatic hypoglycemia [typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤ 70 mg/dL (3.9 mmol/L)]; Severe [an event requiring assistance of another person to actively administer carbohydrate, glucagon, intravenous glucose or other resuscitative actions] or documented symptomatic hypoglycemia [typical symptoms of hypoglycemia and plasma glucose ≤ 70 mg/dL].



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.


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

Inclusion criteria :

  • Participants with Type 2 Diabetes Mellitus (T2DM) using any types of basal insulin alone or in combination with up to 2 OADs.
  • Participants have given written informed consent to participate in the study in accordance with local regulations.

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 (e.g., insulin glargine, Neutral Protamine Hagedorn (NPH), detemir, or degludec) for less than 6 months before Screening.
  • Dose of basal insulin (e.g., insulin glargine, NPH, detemir, or degludec) not stable for 8 weeks before Screening (i.e., 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 (e.g., insulin glargine, NPH, detemir, or degludec), i.e., prandial or rapid-acting insulins, short-acting insulins, glucagon-like peptide 1 (GLP-1) receptor agonists, or inhaled prandial insulin (Afrezza) within 8 weeks of Screening.
  • Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, or empagliflozin) within 3 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.
  • Participants 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 (e.g., genetic hemoglobin (Hb) variants) compromising the reliability of HbA1c assessment or medical conditions that affect interpretation of HbA1c results (e.g., blood transfusion or severe blood loss in the last 3 months prior to randomization, any condition that shortens erythrocyte survival).
  • Participants 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.
  • Participants unwilling to perform self-monitoring of blood glucose (SMBG), complete the patient diary, or comply with study visits and other study procedures as required per protocol.
  • 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 blood pressure measurements >180 mmHg (systolic blood pressure [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).

The above information is not intended to contain all considerations relevant to a participant'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): NCT03285594


Locations
Show Show 106 study locations
Sponsors and Collaborators
Lexicon Pharmaceuticals
Sanofi
Investigators
Layout table for investigator information
Study Director: Suman Wason, MD Lexicon Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Lexicon Pharmaceuticals:
Study Protocol  [PDF] March 12, 2018
Statistical Analysis Plan  [PDF] December 5, 2019

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Responsible Party: Lexicon Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03285594    
Other Study ID Numbers: EFC14868
2016-001804-43 ( EudraCT Number )
U1111-1190-7567 ( Other Identifier: UTN )
First Posted: September 18, 2017    Key Record Dates
Results First Posted: May 11, 2021
Last Update Posted: May 11, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin Glargine
(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action