CompletedNCT03242018SOTA-CKD4Updated Jun 25, 2021Results posted

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

A Phase 3 interventional study of Placebo and Sotagliflozin in Type 2 Diabetes Mellitus and Chronic Kidney Disease Stage 4, sponsored by Lexicon Pharmaceuticals. Completed at 106 sites in 15 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-25.

Sponsored by Lexicon Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 277
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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

Read the detailed 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.

Conditions studied

Type 2 Diabetes Mellitus
Chronic Kidney Disease Stage 4

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In context

Kidney Diseases

3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.

This study's enrollment of 277 is above the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.

Browse Kidney Diseases studies →

Lead sponsor

Lexicon Pharmaceuticals is the lead sponsor of 60 studies on the registry; none are open to participants now.

Of its 18 completed or terminated interventional studies of FDA-regulated products, 15 (83%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 277 participants (actual)

Study arms

Placebo comparator
Placebo
Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 milligrams \[mg\] in appearance) orally once daily for up to 56 weeks.
Drug: Placebo
Experimental
Sotagliflozin 200 mg
Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 56 weeks.
Drug: Placebo · Drug: Sotagliflozin
Experimental
Sotagliflozin 400 mg
Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56 weeks.
Drug: Sotagliflozin

Interventions

DrugPlacebo
Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.
DrugSotagliflozin
Sotagliflozin 200 mg, tablet, orally, once daily.
Also known as: SAR439954

What researchers measure

Primary outcomes

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.
Time frame: Baseline to Week 26

Secondary outcomes

Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Change From Baseline in Body Weight at Week 26
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 26
Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 12
Change From Baseline in SBP at Week 12 for All Participants
An ANCOVA model was used for the analysis.
Time frame: Baseline to Week 12
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.
Time frame: Baseline to Week 26
Percentage of Participants With HbA1c <6.5% at Week 26
Time frame: Week 26
Percentage of Participants With HbA1c <7.0% at Week 26
Time frame: Week 26
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).
Time frame: First dose of study drug to last dose of study drug (up to 56.3 weeks) + 4 weeks

Other outcomes

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 \[typical symptoms of hypoglycemia and plasma glucose ≤ 70 mg/dL\].
Time frame: up to 56.3 weeks

Results

Posted Jun 25, 2021

Participant flow

Participants took part in the study at 106 investigative sites in United States, Argentina, Brazil, Colombia, Germany, Hungary, Israel, Italy, Mexico, Poland, Romania, Russian Federation, South Africa, Spain, Ukraine from 16 August 2017 to 11 December 2019.

Participant flow — Overall Study
Milestone	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Started	93	92	92
Completed	75	78	78
Not completed	18	14	14
Withdrew: Adverse event	7	7	6
Withdrew: Lost to follow-up	2	2	2
Withdrew: At the participant's own request	5	1	4
Withdrew: Reason not specified	3	4	1
Withdrew: Study terminated by sponsor	1	0	1

Outcome measures

PrimaryChange From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo

An analysis of covariance (ANCOVA) model was used for the analysis.

Time frame:: Baseline to Week 26
Reported as:: Least squares mean · percentage of HbA1c

Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo
percentage of HbA1c	Placebo	Sotagliflozin 400 mg
Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo	-0.11 ± 0.151	-0.40 ± 0.131

Statistical analysis

Placebo vs Sotagliflozin 400 mg · ANCOVA · p = 0.0962 · Difference in least square (ls) means: -0.29 · 95% CI -0.628 to 0.051

SecondaryChange From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo