Clinical trial NCT01441232: A Study to Evaluate the Pharmacodynamic Effects of Single-Dose Co-Administration of LX4211 With Januvia® in Type 2 Diabetics
Official title: A Phase 1, Open-label, 3-period, 3-treatment, Single Dose Crossover Study to Evaluate the Pharmacodynamic Effects of LX4211 When Administered Concurrently With JANUVIA® (Sitagliptin) 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: 2011-09-27
Enrollment: 18
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 study is intended to evaluate the pharmacodynamics, safety, and tolerability of LX4211 when administered concurrently with sitagliptin (Januvia®) in patients with Type 2 Diabetes Mellitus.


Eligibility criteria: Inclusion Criteria:

* Adults aged 18 to 65 years of age
* History of Type 2 Diabetes Mellitus for at least 3 months prior to Screening, with HgbA1c values of 6.5 to 10.5% and C-peptide ≥1.0 ng/mL
* Body mass index (BMI) ≤45 kg/sq m
* Willing and able to self-monitor blood glucose
* Able to provide written informed consent

Exclusion Criteria:

* History of Type 1 diabetes mellitus, diabetic ketoacidosis, hyperosmolar nonketotic syndrome, or diabetes resulting from pancreatic disorder or secondary diabetes
* Current use of any blood glucose lowering agent other than metformin
* History of renal disease or clinically significant abnormal kidney function tests at Screening or Day -2
* Presence of active hepatic disease or clinically significant abnormal liver function tests at Screening or Day -2
* History of myocardial infarction, severe/unstable angina, or coronary revascularization procedure within 6 months of Day -2
* History of clinically significant cardiac arrhythmias within 1 year of Day -2
* Congestive heart failure and/or New York Heart Association (NYHA) class III or IV symptoms of heart failure
* Subjects with uncontrolled Stage 3 hypertension
* History of 2 or more emergency room visits, doctor's visits, or hospitalizations due to hypoglycemia within 6 months of Day -2
* History of alcohol or drug abuse within 12 months of Screening
* History of bowel resection \> 20 cm, any malabsorptive disorder, severe gastroparesis, and GI procedure for the purpose of weight loss that would slow gastric emptying
* History of HIV or hepatitis C
* Major surgery within 3 months of Day -2 or any planned surgery during the study
* History of any active infection within 2 weeks of Day -2
* History of pancreatitis
* History of any malignancy within the last 5 years which would affect the diagnosis or assessment of LX4211 or sitagliptin
* History of any serious adverse reaction or hypersensitivity to LX4211 or sitagliptin
* Presence of any clinically significant physical, laboratory, or ECG findings or any concurrent condition at Screening that may interfere with the study in the opinion of the investigator
* Triglycerides \> 1000 mg/dL at Screening or Day -2
* Donation or loss of \>400 mL of blood or blood product within 8 weeks prior to Day -2
* Use of any tobacco product for the duration of study participation
* Use of corticosteroids within 2 weeks of Day 1
* Use of digoxin or warfarin within 2 weeks prior to Screening

Primary outcomes:
measure: Change from baseline in gut hormones
timeFrame: Days 1, 8, and 15
Secondary outcomes:
measure: Change from baseline in fasting plasma glucose
timeFrame: Days 1, 8, and 15
measure: Change from baseline in postprandial glucose
timeFrame: Days 1, 8, and 15
measure: Change from baseline in insulin
timeFrame: Days 1, 8, and 15
measure: Change from baseline in peptide YY
timeFrame: Days 1, 8, and 15
measure: Change from baseline in urinary glucose excretion
timeFrame: Days 1, 8, and 15
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Lexicon Investigational Site
state: Texas
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Ikenna Ogbaa, MD
role: STUDY_DIRECTOR
References:
citation: Zambrowicz B, Ding ZM, Ogbaa I, Frazier K, Banks P, Turnage A, Freiman J, Smith M, Ruff D, Sands A, Powell D. Effects of LX4211, a dual SGLT1/SGLT2 inhibitor, plus sitagliptin on postprandial active GLP-1 and glycemic control in type 2 diabetes. Clin Ther. 2013 Mar;35(3):273-285.e7. doi: 10.1016/j.clinthera.2013.01.010. Epub 2013 Feb 21.