Study to Evaluate the Pharmacodynamic and Pharmacokinetic Effects of LX4211 in Subjects With Type 2 Diabetes and Renal Impairment

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01555008
• Other study ID #: LX4211.1-107-DM
• Secondary ID: LX4211.107
• Status: Completed
• Phase: Phase 1
• First received: March 7, 2012
• Last updated: September 6, 2013
• Start date: March 2012

Study information

• Verified date: September 2013
• Source: Lexicon Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Renal Impairment
• Renal Insufficiency
• Type 2 Diabetes Mellitus

Intervention

Drug:
• LX4211
Subjects will receive LX4211 once daily for 7 days
• LX4211 Placebo
Subjects will receive LX4211 placebo once daily for 7 days

Locations

Country	Name	City	State
United States	Lexicon Investigational Site	Anniston	Alabama
United States	Lexicon Investigational Site	Chula Vista	California
United States	Lexicon Investigational Site	Edgewater	Florida
United States	Lexicon Investigational Site	Minneapolis	Minnesota
United States	Lexicon Investigational Site	Renton	Washington
United States	Lexicon Investigational Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in postprandial glucose		baseline to 7 days	No
Secondary	Number of subjects experiencing an adverse event		7 days	Yes
Secondary	Change from baseline in fasting plasma glucose		baseline to 7 days	No
Secondary	Change from baseline in glucagon-like peptide 1 (Glp-1)		baseline to 7 days	No
Secondary	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	No