Clinical trial NCT01555008: Study to Evaluate the Pharmacodynamic and Pharmacokinetic Effects of LX4211 in Subjects With Type 2 Diabetes and Renal Impairment
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Pharmacodynamic and Pharmacokinetic Effects of LX4211 in Subjects With Type 2 Diabetes Mellitus and Moderate to Severe Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Renal Impairment
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-03-15
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in postprandial glucose
timeFrame: baseline to 7 days
Secondary outcomes:
measure: Number of subjects experiencing an adverse event
timeFrame: 7 days
measure: Change from baseline in fasting plasma glucose
timeFrame: baseline to 7 days
measure: Change from baseline in glucagon-like peptide 1 (Glp-1)
timeFrame: baseline to 7 days
measure: Area Under Curve (AUC)
timeFrame: Days 1 and 7; predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Lexicon Investigational Site
state: Alabama
city: Chula Vista
country: United States
facility: Lexicon Investigational Site
state: California
city: Edgewater
country: United States
facility: Lexicon Investigational Site
state: Florida
city: Minneapolis
country: United States
facility: Lexicon Investigational Site
state: Minnesota
city: San Antonio
country: United States
facility: Lexicon Investigational Site
state: Texas
city: Renton
country: United States
facility: Lexicon Investigational Site
state: Washington
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Ike Ogbaa, M.D.
role: STUDY_DIRECTOR
References:
citation: Zambrowicz B, Lapuerta P, Strumph P, Banks P, Wilson A, Ogbaa I, Sands A, Powell D. LX4211 therapy reduces postprandial glucose levels in patients with type 2 diabetes mellitus and renal impairment despite low urinary glucose excretion. Clin Ther. 2015 Jan 1;37(1):71-82.e12. doi: 10.1016/j.clinthera.2014.10.026. Epub 2014 Dec 17.