A Phase 3 Study to Evaluate the Safety of Sotagliflozin in Patients With Type 1 Diabetes Who Have Inadequate Glycemic Control With Insulin Therapy Alone

Type 1 Diabetes Mellitus (T1DM) Clinical Trial

— inTandem3  

Official title:

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Net Clinical Benefit of Sotagliflozin as Adjunct to Insulin Therapy in Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02531035
• Other study ID #: LX4211.1-312-T1DM
• Secondary ID: LX4211.312
• Status: Completed
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: April 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 designed to demonstrate the net benefit of sotagliflozin versus placebo in patients with Type 1 Diabetes (T1D).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1405
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• 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 T1DM made at least 1 year prior to informed consent

• Participants were being treated with insulin or insulin analog

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

• At the Screening Visit, A1C was between 7.0% to 11.0%

• Females of childbearing potential used an adequate method of contraception and had 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 screening

• Chronic systemic corticosteroid use

• Type 2 diabetes mellitus (T2DM), or severely uncontrolled T1D as determined by the Investigator

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• High Level of Sugar (Glucose) in the Blood
• Type 1 Diabetes Mellitus (T1DM)

Intervention

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

Locations

Country	Name	City	State
Argentina	Lexicon Investigational Site	Buenos Aires
Argentina	Lexicon Investigational Site	Buenos Aires
Argentina	Lexicon Investigational Site	Córdoba	Cordoba
Australia	Lexicon Investigational Site	Box Hill	Victoria
Australia	Lexicon Investigational Site	Coffs Harbour	New South Wales
Australia	Lexicon Investigational Site	Fitzroy	Victoria
Australia	Lexicon Investigational Site	Herston	Queensland
Australia	Lexicon Investigational Site	Keswick	South Australia
Australia	Lexicon Investigational Site	Merewether	New South Wales
Australia	Lexicon Investigational Site	Parkville	Victoria
Australia	Lexicon Investigational Site	St Leonards	New South Wales
Australia	Lexicon Investigational Site	Wollongong	New South Wales
Belgium	Lexicon Investigational Site	Aalst
Belgium	Lexicon Investigational Site	Gent
Belgium	Lexicon Investigational Site	Sint-Niklaas
Bulgaria	Lexicon Investigational Site	Plovdiv
Bulgaria	Lexicon Investigational Site	Ruse
Bulgaria	Lexicon Investigational Site	Smolyan
Bulgaria	Lexicon Investigational Site	Sofia
Bulgaria	Lexicon Investigational Site	Sofia
Bulgaria	Lexicon Investigational Site	Varna
Canada	Lexicon Investigational Site	Barrie	Ontario
Canada	Lexicon Investigational Site	Halifax	Nova Scotia
Canada	Lexicon Investigational Site	London	Ontario
Canada	Lexicon Investigational Site	Markham	Ontario
Canada	Lexicon Investigational Site	Oakville	Ontario
Canada	Lexicon Investigational Site	Sherbrooke	Quebec
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
Colombia	Lexicon Investigational Site	Atlantico
Colombia	Lexicon Investigational Site	Cundinamarca
Colombia	Lexicon Investigational Site	Cundinamarca
Colombia	Lexicon Investigational Site	Cundinamarca
Czechia	Lexicon Investigational Site	Krnov
Czechia	Lexicon Investigational Site	Olomouc
Czechia	Lexicon Investigational Site	Ostrava
Czechia	Lexicon Investigational Site	Praha 10
Czechia	Lexicon Investigational Site	Praha 4
Czechia	Lexicon Investigational Site	Praha 5
France	Lexicon Investigational Site	Corbeil-Essonnes
France	Lexicon Investigational Site	Pierre-Bénite
Germany	Lexicon Investigational Site	Aschaffenburg
Germany	Lexicon Investigational Site	Asslar
Germany	Lexicon Investigational Site	Mainz	Palatinate
Germany	Lexicon Investigational Site	Münster	Westphalia
Germany	Lexicon Investigational Site	Sulzbach	Rosenberg Bavaria
Hungary	Lexicon Investigational Site	Budapest
Hungary	Lexicon Investigational Site	Budapest
Hungary	Lexicon Investigational Site	Budapest
Hungary	Lexicon Investigational Site	Budapest
Hungary	Lexicon Investigational Site	Eger
Hungary	Lexicon Investigational Site	Esztergom
Hungary	Lexicon Investigational Site	Gyor
Hungary	Lexicon Investigational Site	Sátoraljaújhely
Israel	Lexicon Investigational Site	Holon
Israel	Lexicon Investigational Site	Petach-Tikvah
Israel	Lexicon Investigational Site	Petah Tikva
Israel	Lexicon Investigational Site	Rehovot
Israel	Lexicon Investigational Site	Tel Hashomer
Italy	Lexicon Investigational Site	Bologna
Italy	Lexicon Investigational Site	Catania
Italy	Lexicon Investigational Site	Catania
Italy	Lexicon Investigational Site	Latina
Italy	Lexicon Investigational Site	Milan
Italy	Lexicon Investigational Site	Rome
New Zealand	Lexicon Investigational Site	Christchurch
New Zealand	Lexicon Investigational Site	Christchurch	Canterbury
New Zealand	Lexicon Investigational Site	Dunedin	Otago
New Zealand	Lexicon Investigational Site	Epsom	Auckland
New Zealand	Lexicon Investigational Site	Newtown	Wellington
New Zealand	Lexicon Investigational Site	Otahuhu
New Zealand	Lexicon Investigational Site	Takapuna	Auckland
Poland	Lexicon Investigational Site	Gdynia
Poland	Lexicon Investigational Site	Katowice
Poland	Lexicon Investigational Site	Katowice
Poland	Lexicon Investigational Site	Lublin
Poland	Lexicon Investigational Site	Warsaw
Poland	Lexicon Investigational Site	Warsaw
Poland	Lexicon Investigational Site	Warszawa
Slovakia	Lexicon Investigational Site	Bardejov
Slovakia	Lexicon Investigational Site	Bratislava
Slovakia	Lexicon Investigational Site	Bratislava
Slovakia	Lexicon Investigational Site	Levice
South Africa	Lexicon Investigational Site	Bloemfontein
South Africa	Lexicon Investigational Site	Cape Town
South Africa	Lexicon Investigational Site	Cape Town
South Africa	Lexicon Investigational Site	Goodwood	Cape Town
South Africa	Lexicon Investigational Site	Johannesburg
South Africa	Lexicon Investigational Site	Middelburg	Mpumalanga
South Africa	Lexicon Investigational Site	Port Elizabeth
Spain	Lexicon Investigational Site	Barcelona
Spain	Lexicon Investigational Site	Barcelona
Spain	Lexicon Investigational Site	Malaga
Spain	Lexicon Investigational Site	Sevilla
Spain	Lexicon Investigational Site	Sevilla
United Kingdom	Lexicon Investigational Site	Blackburn
United Kingdom	Lexicon Investigational Site	Dundee	Scotland
United Kingdom	Lexicon Investigational Site	Guildford
United Kingdom	Lexicon Investigational Site	Leicester
United Kingdom	Lexicon Investigational Site	Northampton
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	Bend	Oregon
United States	Lexicon Investigational Site	Bloomfield Hills	Michigan
United States	Lexicon Investigational Site	Boston	Massachusetts
United States	Lexicon Investigational Site	Bronx	New York
United States	Lexicon Investigational Site	Chapel Hill	North Carolina
United States	Lexicon Investigational Site	Concord	California
United States	Lexicon Investigational Site	Escondido	California
United States	Lexicon Investigational Site	Grand Forks	North Dakota
United States	Lexicon Investigational Site	Greenville	North Carolina
United States	Lexicon Investigational Site	La Jolla	California
United States	Lexicon Investigational Site	Las Vegas	Nevada
United States	Lexicon Investigational Site	Macon	Georgia
United States	Lexicon Investigational Site	Morehead City	North Carolina
United States	Lexicon Investigational Site	New Haven	Connecticut
United States	Lexicon Investigational Site	New Orleans	Louisiana
United States	Lexicon Investigational Site	Omaha	Nebraska
United States	Lexicon Investigational Site	Orlando	Florida
United States	Lexicon Investigational Site	Rockville	Maryland
United States	Lexicon Investigational Site	Roswell	Georgia
United States	Lexicon Investigational Site	Salt Lake City	Utah
United States	Lexicon Investigational Site	San Antonio	Texas
United States	Lexicon Investigational Site	San Marcos	California
United States	Lexicon Investigational Site	Seattle	Washington
United States	Lexicon Investigational Site	Shavano Park	Texas
United States	Lexicon Investigational Site	Sioux Falls	South Dakota
United States	Lexicon Investigational Site	Ventura	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,  Argentina,  Australia,  Belgium,  Bulgaria,  Canada,  Colombia,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  New Zealand,  Poland,  Slovakia,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With A1C <7.0% at Week 24 and No Episode of Severe Hypoglycemia and No Episode of Diabetic Ketoacidosis (DKA) After Randomization	The primary composite endpoint included blood samples for the assessment of Hemoglobin A1C to determine the participants with a value <7.0%. A central blinded adjudication process determined whether participants experienced either DKA or Severe Hypoglycemia.	Week 24
Secondary	Change From Baseline in A1C	Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. Least Squares (LS) means were obtained from a mixed-effects model for repeated measures (MMRM) model including all available post baseline data. A negative change from Baseline (a lower AIC value at Week 24) indicates an improvement.	Baseline to Week 24
Secondary	Absolute Change From Baseline in Body Weight	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 Systolic Blood Pressure (SBP) in the Subset of Participants With Baseline SBP >=130 Millimeter of Mercury (mmHg)	An automatic sphygmomanometer was used with instructions on blood pressure measurements to allow for standardization. Week 16 was used because the protocol required Investigators to keep participant's hypertensive medications stable between Baseline and Week 16, unless a change was required for safety reasons. Baseline was defined as the last value collected prior to the first does of double-blind study medication. LS means were obtained from MMRM model including all available post baseline values. A negative change indicates a decrease in SBP between Baseline and Week 16.	Baseline to Week 16
Secondary	Percent Change From Baseline in Mean Daily Bolus Insulin Dose	The mean bolus insulin dose in international units/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 percent change from Baseline indicated a reduction in the amount of bolus insulin used and a positive percent change from Baseline indicated an increase in the amount of bolus insulin used between Baseline and Week 24.	Baseline to Week 24