Efficacy, Safety, and Tolerability Study of Sotagliflozin as Adjunct Therapy in Adult Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy

Type 1 Diabetes Mellitus Clinical Trial

— inTandem1  

Official title:

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of LX4211 as Adjunct Therapy in Adult Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02384941
• Other study ID #: LX4211.1-309-T1DM
• Status: Completed
• Phase: Phase 3
• Start date: March 2015
• Est. completion date: February 2017

Study information

• Verified date: February 2020
• Source: Lexicon Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 3 study was intended to demonstrate superiority of either sotagliflozin high dose or low dose versus placebo on glycosylated hemoglobin A1C (A1C) reduction at Week 24 when used as an adjunct in adult participants with type 1 diabetes mellitus (T1D) who have inadequate glycemic control with insulin therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 793
• Est. completion date: February 2017
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants had given written informed consent to participate in the study in accordance with local regulations.

• Adult participants 18 years and older with a diagnosis of T1D made at least 1 year prior to informed consent.

• Participants were being treated with insulin or insulin analog delivered. via continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).

• Willing and able to perform self-monitored blood glucose (SMBG) and complete the study diary as required per protocol.

• At the Screening Visit, A1C must be between 7.0% to 11.0%.

• Females of childbearing potential must use an adequate method of contraception and have a negative pregnancy test .

Exclusion Criteria:

• Use of antidiabetic agent other than insulin or insulin analog at the time of screening.

• Use of sodium-glucose cotransporter (SGLT) inhibitors within 8 weeks prior to randomization.

• Chronic systemic corticosteroid use.

• Type 2 diabetes mellitus (T2D), or severely uncontrolled T1D as determined by the Investigator.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Placebo
Placebo once daily, before first meal of the day.
• Sotagliflozin
Sotagliflozin once daily, before first meal of the day.

Locations

Country	Name	City	State
Canada	Lexicon Investigational Site	Barrie	Ontario
Canada	Lexicon Investigational Site	Calgary	Alberta
Canada	Lexicon Investigational Site	Halifax	Nova Scotia
Canada	Lexicon Investigational Site	Hamilton	Ontario
Canada	Lexicon Investigational Site	London	Ontario
Canada	Lexicon Investigational Site	Montreal	Quebec
Canada	Lexicon Investigational Site	Ottawa	Ontario
Canada	Lexicon Investigational Site	St. Laurent	Quebec
Canada	Lexicon Investigational Site	Thornhill	Ontario
Canada	Lexicon Investigational Site	Toronto	Ontario
Canada	Lexicon Investigational Site	Vancouver	British Columbia
Canada	Lexicon Investigational Site	Winnipeg	Manitoba
United States	Lexicon Investigational Site	Albany	New York
United States	Lexicon Investigational Site	Asheville	North Carolina
United States	Lexicon Investigational Site	Atlanta	Georgia
United States	Lexicon Investigational Site	Aurora	Colorado
United States	Lexicon Investigational Site	Austin	Texas
United States	Lexicon Investigational Site	Baltimore	Maryland
United States	Lexicon Investigational Site	Bangor	Maine
United States	Lexicon Investigational Site	Birmingham	Alabama
United States	Lexicon Investigational Site	Boston	Massachusetts
United States	Lexicon Investigational Site	Chapel Hill	North Carolina
United States	Lexicon Investigational Site	Chattanooga	Tennessee
United States	Lexicon Investigational Site	Chattanooga	Tennessee
United States	Lexicon Investigational Site	Chesapeake	Virginia
United States	Lexicon Investigational Site	Chesterfield	Missouri
United States	Lexicon Investigational Site	Columbus	Ohio
United States	Lexicon Investigational Site	Crystal Lake	Illinois
United States	Lexicon Investigational Site	Dallas	Texas
United States	Lexicon Investigational Site	Dallas	Texas
United States	Lexicon Investigational Site	Dallas	Texas
United States	Lexicon Investigational Site	Detroit	Michigan
United States	Lexicon Investigational Site	Elgin	Illinois
United States	Lexicon Investigational Site	Escondido	California
United States	Lexicon Investigational Site	Fleming Island	Florida
United States	Lexicon Investigational Site	Greenbrae	California
United States	Lexicon Investigational Site	Greer	South Carolina
United States	Lexicon Investigational Site	Henderson	Nevada
United States	Lexicon Investigational Site	Honolulu	Hawaii
United States	Lexicon Investigational Site	Houston	Texas
United States	Lexicon Investigational Site	Houston	Texas
United States	Lexicon Investigational Site	Huntington Beach	California
United States	Lexicon Investigational Site	Jacksonville	Florida
United States	Lexicon Investigational Site	Jacksonville	Florida
United States	Lexicon Investigational Site	La Jolla	California
United States	Lexicon Investigational Site	Las Vegas	Nevada
United States	Lexicon Investigational Site	Lawrenceville	Georgia
United States	Lexicon Investigational Site	Lexington	Kentucky
United States	Lexicon Investigational Site	Little Rock	Arkansas
United States	Lexicon Investigational Site	Longmont	Colorado
United States	Lexicon Investigational Site	Los Angeles	California
United States	Lexicon Investigational Site	Memphis	Tennessee
United States	Lexicon Investigational Site	Morehead City	North Carolina
United States	Lexicon Investigational Site	New Port Richey	Florida
United States	Lexicon Investigational Site	New York	New York
United States	Lexicon Investigational Site	Oklahoma City	Oklahoma
United States	Lexicon Investigational Site	Omaha	Nebraska
United States	Lexicon Investigational Site	Orange	California
United States	Lexicon Investigational Site	Ormond Beach	Florida
United States	Lexicon Investigational Site	Palm Springs	California
United States	Lexicon Investigational Site	Portland	Oregon
United States	Lexicon Investigational Site	Rapid City	South Dakota
United States	Lexicon Investigational Site	Renton	Washington
United States	Lexicon Investigational Site	Roswell	Georgia
United States	Lexicon Investigational Site	Saint Louis	Missouri
United States	Lexicon Investigational Site	San Antonio	Texas
United States	Lexicon Investigational Site	San Mateo	California
United States	Lexicon Investigational Site	Schertz	Texas
United States	Lexicon Investigational Site	Seattle	Washington
United States	Lexicon Investigational Site	Springfield	Illinois
United States	Lexicon Investigational Site	Tarzana	California
United States	Lexicon Investigational Site	Topeka	Kansas
United States	Lexicon Investigational Site	Tustin	California
United States	Lexicon Investigational Site	Walnut Creek	California
United States	Lexicon Investigational Site	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in A1C at Week 24	Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. Least square (LS) means were obtained from a mixed-effects model for repeated measures (MMRM) that included fixed, categorical effects of treatment, randomization strata of insulin delivery method (MDI, CSII), randomization strata of Week -2 A1C (<= 8.5%, >8.5%), time (study week), a treatment-by-time interaction, and baseline A1C-by-time interaction as a covariate. A negative change from Baseline (a lower A1C value at Week 24) indicates an improvement.	Baseline to Week 24
Secondary	Percentage of Participants With A1C <7.0% (at Week 24) and No Episode of Severe Hypoglycemia and No Episode of Diabetic Ketoacidosis (DKA) Upto Week 24	Blood samples were collected for the assessment of Hemoglobin A1C to determine the participants with A1C value <7.0%. A central blinded adjudication process determined whether participants experienced either DKA or Severe Hypoglycemia. Only positively adjudicated severe hypoglycemia and diabetic ketoacidosis were included in the analysis.	Baseline to Week 24
Secondary	Absolute Change From Baseline in Body Weight at Week 24	Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model. A negative change from Baseline indicates a loss in body weight from Baseline to Week 24.	Baseline to Week 24
Secondary	Change From Baseline in Mean Daily Bolus Insulin Dose at Week 24	The mean bolus insulin dose in international units per day (IU/day) for Week 24 was the average over the 3 to 5 days prior to the Week 24 visit. The Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model including all available post Baseline values. A negative change from Baseline indicated a reduction in the amount of bolus insulin used between Baseline and Week 24.	Baseline to Week 24
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	The Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model including all available post baseline values. A negative change from baseline indicates a lower glucose at Week 24 compared to baseline.	Baseline to Week 24
Secondary	Change From Baseline in Diabetes Total Treatment Satisfaction Scores as Measured by Total Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Scores at Week 24	DTSQs is a diabetes-specific measure used to evaluate overall treatment satisfaction and perception of hyperglycemia and hypoglycemia events. It consists of 8 items and the response categories for all items were on a 7-point likert scale.The DTSQs response options ranged from 0 (very dissatisfied) to 6 (very satisfied). Responses to item 1, 4, 5, 6, 7 and 8 were summarized to determine the total treatment satisfaction score which ranged from 0 (very dissatisfied) to 36 (very satisfied), with a higher score corresponding to higher satisfaction . LS means were obtained from MMRM model including all available post baseline values. A positive change from baseline indicates improvement.	Baseline to Week 24
Secondary	Change From Baseline in Diabetes Distress Scores as Measured by 2-item Diabetes Distress Screening Scale (DDS2) Scores at Week 24	The DDS2 is a 2-item diabetes distress screening instrument where respondents rated, on a 6-point scale, the degree to which the following items caused distress: (1) feeling overwhelmed by the demands of living with diabetes, and (2) feeling that I am often failing with my diabetes regimen using a 6-point scale: where 1=no distress to 6=severe distress for a total possible score of 2 (not a problem) to 12 (very serious problem), with higher score corresponding to higher distress. LS means were obtained from MMRM model including all available post baseline values. A negative change from baseline indicates improvement.	Baseline to Week 24
Secondary	Percent Change From Baseline in Body Weight at Week 24	Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model. A negative percent change from baseline indicates a loss in body weight from baseline to Week 24.	Baseline to Week 24