Clinical trial NCT03386344: Efficacy and Bone Safety of Sotagliflozin 400 and 200 mg Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control
Official title: A 26-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Study With a 78-week Extension Period to Evaluate the Efficacy and Bone Safety of Sotagliflozin in Patients 55 Years or Older With Type 2 Diabetes Mellitus and Inadequate Glycemic Control
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-12-29
Enrollment: 376
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1c (Hb1Ac) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control on diet and exercise only or with a stable antidiabetes regimen.

Detailed description: Study duration per participant is approximately 110 weeks (Screening period of up to 2 weeks, 2 week single-blind run-in period), a 26-week double-blind core treatment period, a 78-week double-blind extension period, and a 2- week post treatment follow up period.

Dual-energy X-ray absorptiometry (DXA) scans will be performed to assess Bone Mineral Density and Fat vs. Lean body mass at baseline and Weeks 26, 52, and 104.

Eligibility criteria: Inclusion criteria :

* Participants with T2D managed with diet and exercise only or with a stable antidiabetes regimen (in monotherapy or combination therapy that can include oral antidiabetes medications, insulin, or glucagon-like peptide-1 agonists) for more than 12 weeks.
* Participants has given written informed consent to participate in the study in accordance with local regulations.

Exclusion criteria:

* Age \<55 years.
* Women who have been postmenopausal (or undergone bilateral oophorectomy) for less than 5 years.
* Type 1 diabetes mellitus.
* Body mass index (BMI) ≤20 or \>45 kilogram per meter square kg/m\^2 or bodyweight that exceeds the weight limits of the DXA scanner.
* Hemoglobin A1C (HbA1c) \<7.0% or HbA1c \>11.0%.
* Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor or thiazolidinedione within 24 months.
* Bone mineral density (BMD) T- score \<-2.0 at any site (ie, lumbar spine, total hip, or femoral neck).
* History of fracture within 12 months (except for fractures of the hand/fingers, foot/toes, facial bones, and skull).
* Treatment with medications known to affect bone mass or modify the risk of fractures within 36 months (eg, bisphosphonates, selective estrogen receptor modulators, calcitonin, teriparatide, denosumab, strontium ranelate, growth hormone, aromatase inhibitors, androgen deprivation therapy, carbamazepine, phenytoin, and phenobarbital). Use of hormonal replacement that includes systemic or transdermal estrogen or testosterone is excluded unless is stable for at least 24 months prior to Screening.
* Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at randomization.
* 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.
* Renal disease as defined by an estimated glomerular filtration rate (eGFR) \<30 milliliter per minute (mL/min)/1.73 meter square (m\^2) at the Screening Visit by the 4 variable Modification of Diet in Renal Disease equation.

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

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26
timeFrame: Baseline to Week 26
Secondary outcomes:
measure: Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Week 26
timeFrame: Baseline to Week 26
measure: Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Week 26
timeFrame: Baseline to Week 26
measure: Percent Change From Baseline in Bone Mineral Density (BMD) of Femoral Neck at Week 26
timeFrame: Baseline to Week 26
measure: Change From Baseline in Body Weight at Week 26
timeFrame: Baseline to Week 26
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
timeFrame: Baseline to Week 26
measure: Change From Baseline in Systolic Blood Pressure (SBP) at Week 12
timeFrame: Baseline to Week 12
measure: Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% at Week 26
timeFrame: Week 26
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: up to 106 weeks
Other outcomes:
Locations:
city: Escondido
country: United States
facility: Investigational Site Number 8409009
state: California
city: Greenbrae
country: United States
facility: Investigational Site Number 8409010
state: California
city: Walnut Creek
country: United States
facility: Investigational Site Number 8409005
state: California
city: Columbus
country: United States
facility: Investigational Site Number 8409012
state: Georgia
city: Evansville
country: United States
facility: Investigational Site Number 8409011
state: Indiana
city: Wichita
country: United States
facility: Investigational Site Number 8409014
state: Kansas
city: Albuquerque
country: United States
facility: Investigational Site Number 8409015
state: New Mexico
city: Chapel Hill
country: United States
facility: Investigational Site Number 8409002
state: North Carolina
city: Wilmington
country: United States
facility: Investigational Site Number 8409001
state: North Carolina
city: Dayton
country: United States
facility: Investigational Site Number 8409008
state: Ohio
city: Chattanooga
country: United States
facility: Investigational Site Number 8409004
state: Tennessee
city: Austin
country: United States
facility: Investigational Site Number 8409013
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8409003
state: Texas
city: Katy
country: United States
facility: Investigational Site Number 8409007
state: Texas
city: Fremantle
country: Australia
facility: Investigational Site Number 0369003
city: Merewether
country: Australia
facility: Investigational Site Number 0369002
city: Parkville
country: Australia
facility: Investigational Site Number 0369004
city: Brampton
country: Canada
facility: Investigational Site Number 1249003
city: Etobicoke
country: Canada
facility: Investigational Site Number 1249008
city: Pointe-Claire
country: Canada
facility: Investigational Site Number 1249005
city: Thornhill
country: Canada
facility: Investigational Site Number 1249006
city: Thornhill
country: Canada
facility: Investigational Site Number 1249004
city: Vancouver
country: Canada
facility: Investigational Site Number 1249007
city: Victoriaville
country: Canada
facility: Investigational Site Number 1249002
city: Daejeon
country: Korea, Republic of
facility: Investigational Site Number 4109006
city: Guri-Si, Gyeonggi-Do
country: Korea, Republic of
facility: Investigational Site Number 4109005
city: Gyeonggi-Do
country: Korea, Republic of
facility: Investigational Site Number 4109003
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 4109004
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 4109001
city: Aguascalientes, Aguascalientes
country: Mexico
facility: Investigational Site Number 4849006
city: Aguascalientes
country: Mexico
facility: Investigational Site Number 4849001
city: Cuernavaca
country: Mexico
facility: Investigational Site Number 4849003
city: Guadalajara Jalisco
country: Mexico
facility: Investigational Site Number 4849002
city: Monterrey
country: Mexico
facility: Investigational Site Number 4849004
city: Xalapa
country: Mexico
facility: Investigational Site Number 4849005
city: Auckland
country: New Zealand
facility: Investigational Site Number 5549004
city: Christchurch
country: New Zealand
facility: Investigational Site Number 5549003
city: Rotorua
country: New Zealand
facility: Investigational Site Number 5549001
city: Wellington
country: New Zealand
facility: Investigational Site Number 5549002
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number 6439007
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number 6439005
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6439002
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6439003
city: St. Petersburg
country: Russian Federation
facility: Investigational Site Number 6439001
city: Yaroslavl
country: Russian Federation
facility: Investigational Site Number 6439006
city: Changhua
country: Taiwan
facility: Investigational Site Number 1589005
city: New Taipei City
country: Taiwan
facility: Investigational Site Number 1589008
city: Taichung
country: Taiwan
facility: Investigational Site Number 1589006
city: Taichung
country: Taiwan
facility: Investigational Site Number 1589007
city: Tainan
country: Taiwan
facility: Investigational Site Number 1589001
city: Tainan
country: Taiwan
facility: Investigational Site Number 1589002
city: Taipei
country: Taiwan
facility: Investigational Site Number 1589004
city: Taipei
country: Taiwan
facility: Investigational Site Number 1589003
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Suman Wason, MD
role: STUDY_DIRECTOR
References: