A Study to Evaluate Safety and Effects of Sotagliflozin 400 and 200 mg on Glucose Control in Participants With Type 2 Diabetes, Severe Impairment of Kidney Function and Inadequate Blood Sugar Control

Type 2 Diabetes Mellitus Clinical Trial

— SOTA-CKD4  

Official title:

A Randomized, Double-blind, Placebo-controlled, 3-arm, Parallel-group 52-week Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin in Patients With Type 2 Diabetes Mellitus and Severe Renal Impairment Who Have Inadequate Glycemic Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03242018
• Other study ID #: EFC15166
• Secondary ID: 2016-004906-32U1
• Status: Completed
• Phase: Phase 3
• Start date: August 16, 2017
• Est. completion date: December 11, 2019

Study information

• Verified date: June 2021
• Source: Lexicon Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To demonstrate the superiority of sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1c (HbA1c) reduction at Week 26 in participants with Type 2 diabetes who have inadequate glycemic control and severe renal impairment

Secondary Objectives:

• To assess the effects of sotagliflozin 200 mg versus placebo based on change from baseline in HbA1c

• To assess the effects of sotagloflozin 400 mg and 200 mg versus placebo

• To evaluate the safety of sotagliflozin 400 mg and 200 mg versus placebo

Description:

The study duration is up to 60 weeks including 4 weeks prior to randomization, 52 weeks of randomized treatment and a visit 4 weeks after completion of the randomized treatment period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 277
• Est. completion date: December 11, 2019
• Est. primary completion date: May 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Participants with Type 2 Diabetes (drug-naïve or on antidiabetic therapy) and documented severe renal insufficiency - CKD4 - defined by an estimated glomerular filtration rate (eGFR) equation (based on the 4 variable modification of diet in renal disease (MDRD) equation) of =15 and <30 milliliter per minute (mL/min)/1.73 per meter square (m^2).

• Signed written informed consent to participate in the study in accordance with local regulations.

Exclusion criteria:

• At the time of screening, age <18 years.

• Hemoglobin A1c (HbA1c) <7% or >11%.

• Type 1 diabetes.

• Women of childbearing potential (WOCBP) 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.

• Treatment with an sodium-glucose cotransporter type 2 (SGLT2) inhibitor (canagliflozin, dapagliflozin, empagliflozin) during the last 12 months.

• Uncontrolled high blood pressure, severe anemia, severe cardiovascular problems, such as heart failure, active cancer, or other conditions that the Investigator believes with result in a short life expectancy, 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.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Chronic Kidney Disease Stage 4
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Kidney Diseases
• Renal Insufficiency, Chronic
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Placebo
Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.
• Sotagliflozin
Sotagliflozin 200 mg, tablet, orally, once daily.

Locations

Country	Name	City	State
Argentina	Investigational Site Number 0325001	Buenos Aires
Argentina	Investigational Site Number 0325003	Launs Este
Argentina	Investigational Site Number 0325004	Mar Del Plata
Brazil	Investigational Site Number 0765003	Belém
Brazil	Investigational Site Number 0765001	Fortaleza
Brazil	Investigational Site Number 0765004	Rio De Janeiro
Brazil	Investigational Site Number 0765002	Sao Paulo
Colombia	Investigational Site Number 1705004	Barranquilla
Colombia	Investigational Site Number 1705005	Bogota
Colombia	Investigational Site Number 1705002	Manizales
Colombia	Investigational Site Number 1705001	Zipaquira
Germany	Investigational Site Number 2765001	Frankfurt Am Main
Germany	Investigational Site Number 2765003	Hannover
Germany	Investigational Site Number 2765004	Münster
Hungary	Investigational Site Number 3485005	Baja
Hungary	Investigational Site Number 3485007	Debrecen
Hungary	Investigational Site Number 3485004	Pécs
Israel	Investigational Site Number 3765002	Ashkelon
Israel	Investigational Site Number 3765001	Haifa
Israel	Investigational Site Number 3765007	Kfar-Saba
Israel	Investigational Site Number 3765005	Ramat Gan
Israel	Investigational Site Number 3765004	Rehovot
Israel	Investigational Site Number 3765003	Tel Aviv
Israel	Investigational Site Number 3765006	Zefat
Italy	Investigational Site Number 3805003	Catania
Italy	Investigational Site Number 3805005	Milano
Italy	Investigational Site Number 3805002	Napoli
Italy	Investigational Site Number 3805006	Napoli
Italy	Investigational Site Number 3805001	Pavia
Italy	Investigational Site Number 3805004	Roma
Mexico	Investigational Site Number 4845001	Guadalajara
Mexico	Investigational Site Number 4845004	Guadalajara
Mexico	Investigational Site Number 4845007	Guadalajara Jalisco
Mexico	Investigational Site Number 4845008	Merida, Yucatan
Mexico	Investigational Site Number 4845006	Monterrey, N.L
Mexico	Investigational Site Number 4845003	Morelia
Mexico	Investigational Site Number 4845002	Queretaro
Mexico	Investigational Site Number 4845005	Xalapa
Poland	Investigational Site Number 6165003	Krakow
Poland	Investigational Site Number 6165002	Lodz
Poland	Investigational Site Number 6165004	Oswiecim
Poland	Investigational Site Number 6165005	Pulawy
Poland	Investigational Site Number 6165001	Rzeszow
Romania	Investigational Site Number 6425005	Bacau
Romania	Investigational Site Number 6425002	Bucuresti
Romania	Investigational Site Number 6425003	Bucuresti
Romania	Investigational Site Number 6425007	Hunedoara
Romania	Investigational Site Number 6425004	Lasi
Romania	Investigational Site Number 6425001	Targu-Mures
Russian Federation	Investigational Site Number 6435004	Chelyabinsk
Russian Federation	Investigational Site Number 6435005	Kemerovo
Russian Federation	Investigational Site Number 6435003	Krasnodar
Russian Federation	Investigational Site Number 6435006	Novosibirsk
Russian Federation	Investigational Site Number 6435001	Saint-Petersburg
South Africa	Investigational Site Number 7105003	Cape Town
South Africa	Investigational Site Number 7105004	Cape Town
South Africa	Investigational Site Number 7105001	Johannesburg
South Africa	Investigational Site Number 7105002	Pretoria
Spain	Investigational Site Number 7245005	Barcelona
Spain	Investigational Site Number 7245007	Barcelona
Spain	Investigational Site Number 7245003	Ferrol
Spain	Investigational Site Number 7245009	Granada
Spain	Investigational Site Number 7245006	Madrid
Spain	Investigational Site Number 7245004	Málaga
Spain	Investigational Site Number 7245001	Sevilla
Spain	Investigational Site Number 7245002	Zaragoza
Ukraine	Investigational Site Number 8045004	Chernivtsi
Ukraine	Investigational Site Number 8045006	Kiev
Ukraine	Investigational Site Number 8045001	Kyiv
Ukraine	Investigational Site Number 8045003	Kyiv
Ukraine	Investigational Site Number 8045007	Kyiv
Ukraine	Investigational Site Number 8045002	Zaporizhzhia
United States	Investigational Site Number 8405035	Albany	New York
United States	Investigational Site Number 8405041	Arlington Heights	Illinois
United States	Investigational Site Number 8405004	Beaumont	Texas
United States	Investigational Site Number 8405014	Bronx	New York
United States	Investigational Site Number 8405015	Chula Vista	California
United States	Investigational Site Number 8405021	Clearwater	Florida
United States	Investigational Site Number 8405036	Dallas	Texas
United States	Investigational Site Number 8405009	Dayton	Ohio
United States	Investigational Site Number 8405001	DeLand	Florida
United States	Investigational Site Number 8405034	Flint	Michigan
United States	Investigational Site Number 8405033	Guntersville	Alabama
United States	Investigational Site Number 8405020	Houston	Texas
United States	Investigational Site Number 8405026	Houston	Texas
United States	Investigational Site Number 8405047	Hurst	Texas
United States	Investigational Site Number 8405032	La Jolla	California
United States	Investigational Site Number 8405019	Lake Charles	Louisiana
United States	Investigational Site Number 8405027	Laurelton	New York
United States	Investigational Site Number 8405039	Lawrenceville	Georgia
United States	Investigational Site Number 8405008	Layton	Utah
United States	Investigational Site Number 8405007	Little Rock	Arkansas
United States	Investigational Site Number 8405043	Miami	Florida
United States	Investigational Site Number 8405037	New Bern	North Carolina
United States	Investigational Site Number 8405003	Norco	California
United States	Investigational Site Number 8405012	Norfolk	Nebraska
United States	Investigational Site Number 8405013	Northridge	California
United States	Investigational Site Number 8405006	Ocoee	Florida
United States	Investigational Site Number 8405025	Ormond Beach	Florida
United States	Investigational Site Number 8405005	Phoenix	Arizona
United States	Investigational Site Number 8405016	San Antonio	Texas
United States	Investigational Site Number 8405031	San Antonio	Texas
United States	Investigational Site Number 8405018	San Dimas	California
United States	Investigational Site Number 8405030	Sellersburg	Indiana
United States	Investigational Site Number 8405040	Winchester	Virginia
United States	Investigational Site Number 8405038	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Colombia,  Germany,  Hungary,  Israel,  Italy,  Mexico,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Hypoglycemic Events	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].	up to 56.3 weeks
Primary	Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo	An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline to Week 26
Secondary	Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo	An ANCOVA model was used for the analysis.	Baseline to Week 26
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	An ANCOVA model was used for the analysis.	Baseline to Week 26
Secondary	Change From Baseline in Body Weight at Week 26	An ANCOVA model was used for the analysis.	Baseline to Week 26
Secondary	Change From Baseline in SBP at Week 12 in Participants With Baseline SBP =130 mmHg	An ANCOVA model was used for the analysis.	Baseline to Week 12
Secondary	Change From Baseline in SBP at Week 12 for All Participants	An ANCOVA model was used for the analysis.	Baseline to Week 12
Secondary	Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g)	An ANCOVA model was used for analysis. No Measure of Dispersion was pre-specified to be calculated.	Baseline to Week 26
Secondary	Percentage of Participants With HbA1c <6.5% at Week 26		Week 26
Secondary	Percentage of Participants With HbA1c <7.0% at Week 26		Week 26
Secondary	Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (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 the investigational medicinal product (IMP).	First dose of study drug to last dose of study drug (up to 56.3 weeks) + 4 weeks