Clinical trial NCT01188863: Study of Two Oral Formulations of LX4211 in Patients With Type 2 Diabetes Mellitus
Official title: A Phase 1, Randomized, Open-Label, Three-Way Crossover Study of Two Oral Formulations of LX4211 in Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2010-08-26
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This protocol is intended to compare the effects of both a solid (tablet) and liquid oral dosage form of LX4211 in subjects with type 2 diabetes mellitus.


Eligibility criteria: Inclusion Criteria:

* Adults aged 18 to 65 years of age
* Males and females of non-childbearing potential
* Diagnosis of type 2 diabetes mellitus for at least 6 months prior to screening
* Fasting plasma glucose ≤240 mg/dL
* Body mass index \<42 kg/sq m
* HbA1c of 7-11%
* C-peptide of ≥1.0 ng/mL
* Ability to provide written informed consent

Exclusion Criteria:

* History of type 1 diabetes mellitus, diabetic ketoacidosis, hyperosmolar nonketonic syndrome, incontinence, or nocturia
* Current use of any blood glucose-lowering agent other than metformin
* Exposure to insulin, thiazide, or loop diuretics within 4 weeks prior to screening
* History of HIV, Hepatitis B, or Hepatitis C
* Surgery within 6 months of screening
* Donation or loss of \>400 mL of blood or blood product within 8 weeks prior to start of study
* Use of proteins or antibodies within 12 weeks prior to screening. (Flu shots are allowed.)
* Exposure to any investigational agent or participation in an investigational trial within 30 days of the start of the study
* History of drug or alcohol abuse within 12 months prior to screening.

Primary outcomes:
measure: Maximum observed plasma concentration
timeFrame: Pharmacokinetics samples collected on day of dosing and 24 and 48 hours post-dose (Follow-up).
measure: Time at which maximum observed plasma concentration occurs
timeFrame: Pharmacokinetics samples collected on day of dosing and 24 and 48 hours post-dose (Follow-up).
measure: Half-life of the drug in plasma
timeFrame: Pharmacokinetics samples collected on day of dosing and 24 and 48 hours post-dose (Follow-up).
Secondary outcomes:
measure: Plasma glucose
timeFrame: Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge.
measure: Urinary glucose excretion
timeFrame: Samples collected on Day -1 (Washout), day of dosing, and 24 and 48 hours post-dose (Follow-up).
measure: Insulin
timeFrame: Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge.
measure: Peptide YY
timeFrame: Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge.
measure: Glucagon-like Peptide 1
timeFrame: Samples collected on initial visit; Day -15 and Day -5 (Washout); numerous timepoints on Day -1 (Washout) and day of dosing; 24 hours post-dose (Follow-up); and upon discharge.
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Lexicon Investigational Site
state: Texas
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Joel P. Freiman, MD, MPH
role: STUDY_DIRECTOR
References:
citation: Zambrowicz B, Freiman J, Brown PM, Frazier KS, Turnage A, Bronner J, Ruff D, Shadoan M, Banks P, Mseeh F, Rawlins DB, Goodwin NC, Mabon R, Harrison BA, Wilson A, Sands A, Powell DR. LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther. 2012 Aug;92(2):158-69. doi: 10.1038/clpt.2012.58. Epub 2012 Jul 4.