Clinical trial NCT01916863: Study to Evaluate the Effect of Single Doses of LX4211 and Canagliflozin on Intestinal Glucose Absorption in Healthy Adult Subjects
Official title: A Phase 1, Single-center, Partially Double-blind, Randomized, Single-dose, 3-Period Crossover Study to Assess the Pharmacodynamic Effects of LX4211 and INVOKANA™ (Canagliflozin) in Healthy Subjects Using Stable Isotope Tracer Methods
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-08-06
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effect of LX4211 and the comparator drug canagliflozin on intestinal glucose absorption and metabolism after a single dose in healthy subjects in comparison to placebo.


Eligibility criteria: Inclusion Criteria:

* Adult subjects ≥18 to ≤55 years of age
* Vital signs at Screening in the following ranges: systolic blood pressure, 90-140 mmHg; diastolic blood pressure, 50-90 mmHg; heart rate, 45-100 bpm
* Body mass index (BMI) ≥18 and ≤35 kg/sq m
* Willing and able to provide written informed consent

Exclusion Criteria:

* Use of any medication (prescription, over-the-counter, herbal tea, or supplements) within 7 days of dosing
* Use of any investigational agent or study treatment within 30 days of Day -1
* Use of any protein or antibody-based therapeutic agents within 3 months of Screening
* Prior exposure to LX4211 or canagliflozin
* Daily use of \>5 cigarettes or any tobacco products within 6 weeks prior to Screening and while participating in the study
* History of bariatric surgery or any other gastrointestinal surgery that may induce malabsorption
* History of bowel resection, any malabsorptive disorder, severe gastroparesis, any GI procedure for the purpose of weight loss which would slow gastric emptying
* History of any major surgery within 6 months prior to Screening
* History of any hypersensitivity to the inactive components of LX4211, inactive components of canagliflozin, acetaminophen oral solution or any inactive component of acetaminophen liquid preparation
* History of renal disease or significantly abnormal kidney function tests
* History of hepatic disease or significantly abnormal liver function tests
* History of any active infection within 30 days prior to Day -1
* History of alcohol or substance abuse within 2 years prior to Day 1
* History of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), HIV-1 or HIV-2
* Donation or loss of \>500 mL of blood or blood product within 56 days of Day -1
* positive pregnancy test at Screening or Day -1
* Positive urine screen for drugs of abuse at Screening or Day -1
* Positive breath test for alcohol at Screening or Day -1
* Inability or difficulty swallowing whole tablets
* Unable or unwilling to communicate or cooperate with the Investigator

Primary outcomes:
measure: Change from baseline in rate of glucose appearance after meal (RaO)
timeFrame: Days 1, 8, 15
Secondary outcomes:
measure: Rate of total glucose appearance (RaT)
timeFrame: Days 1, 8, 15
measure: Change from baseline in fasting plasma glucose
timeFrame: Days 1, 8, 15
measure: Change from baseline in postprandial glucose
timeFrame: Days 1, 8, 15
measure: Change from baseline in insulin
timeFrame: Days 1, 8, 15
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Lexicon Investigational Site
state: California
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Paul Strumph, M.D.
role: STUDY_DIRECTOR
References:
citation: Powell DR, Zambrowicz B, Morrow L, Beysen C, Hompesch M, Turner S, Hellerstein M, Banks P, Strumph P, Lapuerta P. Sotagliflozin Decreases Postprandial Glucose and Insulin Concentrations by Delaying Intestinal Glucose Absorption. J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1235-49. doi: 10.1210/clinem/dgz258.