Type 2 Diabetes Mellitus, Renal Impairment
Conditions
Brief summary
This Phase 1 study is intended to assess the pharmacodynamics (PD), pharmacokinetics (PK), safety and tolerability of LX4211 following once daily oral administration in subjects with type 2 diabetes mellitus (T2DM) and moderate to severe renal impairment.
Interventions
DRUGLX4211
Subjects will receive LX4211 once daily for 7 days
DRUGLX4211 Placebo
Subjects will receive LX4211 placebo once daily for 7 days
Sponsors
Lexicon Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adults ≥18 to ≤80 years of age * History of T2DM for at least 6 months prior to screening * Moderate to severe renal impairment and not actively on dialysis * Willing and able to perform self-monitoring of blood glucose * Willing and able to provide written informed consent
Exclusion criteria
* History of type 1 diabetes mellitus, diabetic ketoacidosis (within the previous 6 months), or diabetes resulting from pancreatic disorder or secondary diabetes (from acromegaly and/or Cushing's disease) * Subjects who have received a renal allograft * Subjects expecting to require dialysis or to undergo kidney transplantation within 3 months of study dosing * Presence of active hepatic disease or clinically significant abnormal liver function tests at Screening or planned study Day -1 * Subjects with a history of heart attack, severe/unstable angina, or coronary revascularization procedure within 6 months prior to study Day -2 * History of clinically significant cardiac arrhythmias within 1 year prior to study Day -2 * Subjects with congestive heart failure * Subjects with uncontrolled Stage III hypertension * History of 2 or more emergency room visits, doctors' visits, or hospitalizations due to hypoglycemia within the 6 months prior to planned study Day -2 * History of alcohol or illicit drug abuse within 1 year prior to Screening * History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C * Major surgery within 6 months prior to planned study Day -2 * History of any malignancy within the last 5 years * Triglycerides \>1000 mg/dL at Screening or planned study Day -1 * History of any serious adverse reaction or hypersensitivity to an SGLT inhibitor * Use of corticosteroids within 2 weeks prior to study Day 1 * Use of any investigational drug within 30 days prior to study Day 1, or investigational protein or antibodies within 60 days of Day 1 * Positive urine pregnancy test at Screening * Positive urine screen for illicit drug abuse at Screening * Prior exposure to LX4211
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in postprandial glucose | baseline to 7 days |
Secondary
| Measure | Time frame |
|---|---|
| Area Under Curve (AUC) | Days 1 and 7; predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose |
| Change from baseline in fasting plasma glucose | baseline to 7 days |
| Change from baseline in glucagon-like peptide 1 (Glp-1) | baseline to 7 days |
| Number of subjects experiencing an adverse event | 7 days |
Countries
United States
Outcome results
None listed