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

— inTandem2  

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: NCT02421510
• Other study ID #: LX4211.1-310-T1DM
• Secondary ID: LX4211.3102014-0
• Status: Completed
• Phase: Phase 3
• Start date: May 2015
• Est. completion date: June 23, 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: 782
• Est. completion date: June 23, 2017
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant who gave 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 treated with insulin or insulin analog delivered via continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).

• Willing and were able to perform Self-monitoring of blood glucose (SMBG) and completed the study diary as required per protocol.

• At the Screening Visit, A1C was 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 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
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Sotagliflozin
High dose Sotagliflozin, once daily, before the first meal of the day
• Sotagliflozin
Low dose 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
Austria	Lexicon Investigational Site	Linz
Austria	Lexicon Investigational Site	Vienna
Austria	Lexicon Investigational Site	Vienna
Austria	Lexicon Investigational Site	Vienna
Austria	Lexicon Investigational Site	Vienna
Belgium	Lexicon Investigational Site	Antwerp
Belgium	Lexicon Investigational Site	Brussels
Belgium	Lexicon Investigational Site	Edegem
Belgium	Lexicon Investigational Site	Leuven
Belgium	Lexicon Investigational Site	Sint Niklaas
Bulgaria	Lexicon Investigational Site	Lovech
Bulgaria	Lexicon Investigational Site	Plovdiv
Bulgaria	Lexicon Investigational Site	Ruse
Bulgaria	Lexicon Investigational Site	Smolyan
Bulgaria	Lexicon Investigational Site	Sofia
Bulgaria	Lexicon Investigational Site	Varna
France	Lexicon Investigational Site	Beziers
France	Lexicon Investigational Site	Dijon cedex
France	Lexicon Investigational Site	Nantes
France	Lexicon Investigational Site	Nantes
France	Lexicon Investigational Site	Nîmes
Germany	Lexicon Investigational Site	Duesseldorf
Germany	Lexicon Investigational Site	Hamburg
Germany	Lexicon Investigational Site	Hamburg
Germany	Lexicon Investigational Site	Hannover
Germany	Lexicon Investigational Site	Mainz
Germany	Lexicon Investigational Site	Muenster
Germany	Lexicon Investigational Site	Neuwied
Hungary	Lexicon Investigational Site	Budapest
Hungary	Lexicon Investigational Site	Budapest
Hungary	Lexicon Investigational Site	Budapest
Hungary	Lexicon Investigational Site	Budapest
Hungary	Lexicon Investigational Site	Budapest
Hungary	Lexicon Investigational Site	Gyula
Hungary	Lexicon Investigational Site	Hodmezovasarhely
Hungary	Lexicon Investigational Site	Zalaegerszeg
Israel	Lexicon Investigational Site	Haifa
Israel	Lexicon Investigational Site	Holon
Israel	Lexicon Investigational Site	Jerusalem
Israel	Lexicon Investigational Site	Petah Tikva
Israel	Lexicon Investigational Site	Tel Aviv
Israel	Lexicon Investigational Site	Tel Hashomer
Israel	Lexicon Investigational Site	Zerifin
Italy	Lexicon Investigational Site	Catania
Italy	Lexicon Investigational Site	Milano
Italy	Lexicon Investigational Site	Palermo
Italy	Lexicon Investigational Site	Perugia
Italy	Lexicon Investigational Site	Pisa
Italy	Lexicon Investigational Site	Roma
Lithuania	Lexicon Investigational Site	Jonava
Lithuania	Lexicon Investigational Site	Kaunas
Lithuania	Lexicon Investigational Site	Kaunas
Netherlands	Lexicon Investigational Site	Dordrecht
Poland	Lexicon Investigational Site	Katowice
Poland	Lexicon Investigational Site	Kraków
Poland	Lexicon Investigational Site	Lodz
Poland	Lexicon Investigational Site	Lublin
Poland	Lexicon Investigational Site	Poznan
Poland	Lexicon Investigational Site	Szczecin
Poland	Lexicon Investigational Site	Warsaw
Poland	Lexicon Investigational Site	Warszawa
Poland	Lexicon Investigational Site	Warszawa
Romania	Lexicon Investigational Site	Bacau
Romania	Lexicon Investigational Site	Bucuresti
Romania	Lexicon Investigational Site	Bucuresti
Romania	Lexicon Investigational Site	Buzau
Romania	Lexicon Investigational Site	Galati
Romania	Lexicon Investigational Site	Oradea
Romania	Lexicon Investigational Site	Sibiu
Romania	Lexicon Investigational Site	Targu-Mures
Slovakia	Lexicon Investigational Site	Bratislava
Slovakia	Lexicon Investigational Site	Bratislava
Slovakia	Lexicon Investigational Site	Kosice
Slovakia	Lexicon Investigational Site	Nove Zamky
Slovakia	Lexicon Investigational Site	Sturovo
Slovakia	Lexicon Investigational Site	Vrutky
Spain	Lexicon Investigational Site	Barcelona
Spain	Lexicon Investigational Site	Barcelona
Spain	Lexicon Investigational Site	Granada
Spain	Lexicon Investigational Site	Malaga
Spain	Lexicon Investigational Site	Sevilla
Spain	Lexicon Investigational Site	Sevilla
Spain	Lexicon Investigational Site	Sevilla
Spain	Lexicon Investigational Site	Sevilla
Spain	Lexicon Investigational Site	Valencia
Sweden	Lexicon Investigational Site	Härnösand
Sweden	Lexicon Investigational Site	Kristianstad
Sweden	Lexicon Investigational Site	Stockholm
Switzerland	Lexicon Investigational Site	St. Gallen
United Kingdom	Lexicon Investigational Site	Birmingham
United Kingdom	Lexicon Investigational Site	Blackburn
United Kingdom	Lexicon Investigational Site	Bristol
United Kingdom	Lexicon Investigational Site	Glasgow
United Kingdom	Lexicon Investigational Site	Leeds
United Kingdom	Lexicon Investigational Site	Leicester
United Kingdom	Lexicon Investigational Site	Sheffield

Sponsors (2)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

Austria,  Belgium,  Bulgaria,  France,  Germany,  Hungary,  Israel,  Italy,  Lithuania,  Netherlands,  Poland,  Romania,  Slovakia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

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 reduction of 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) From Baseline to Week 24	The composite endpoint included blood samples for the assessment of Hemoglobin A1C to determine the participants with a value <7.0% and a central blinded adjudication process to determine 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	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/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 and a positive change from baseline indicated an increase 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 level at Week 24 compared to baseline and a positive change from baseline indicates an increase in glucose level at Week 24 compared to baseline.	Baseline to Week 24
Secondary	Change From Baseline in Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score at Week 24	The DTSQ instrument contains 8 items assessing overall treatment satisfaction, treatment convenience and flexibility, satisfaction with understanding of diabetes, willingness to continue present treatment and to recommend it to others, and frequency of unacceptably high and unacceptably low blood glucose levels. 6 items (1, 4, 5, 6, 7 and 8) (excluding perceived hyperglycemia and hypoglycemia items) were scored using a 7- point scale where 0=very dissatisfied to 6= very satisfied for a total possible score of 0 (very dissatisfied) to 36 (very satisfied), where higher scores indicate higher satisfaction from treatment. Two items (Q2 and 3), which were not included, measured perceived hyperglycemia and hypoglycemia, respectively. 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 positive change from baseline indicates improvement.	Baseline to Week 24
Secondary	Change From Baseline in 2-Item Diabetes Distress Screen 2 (DDS2) Score at Week 24	DDS2 is a 2-item diabetes distress screening instrument where participants rated 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 to 12. 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