Clinical trial NCT01173549: A Study of 28431754 (Canagliflozin) on Gastrointestinal Glucose Absorption and Metabolism in Healthy Volunteers
Official title: A Double-Blind, Randomized, Placebo Controlled, 2-Period Crossover Study to Evaluate the Effect of a Single Dose of JNJ-28431754 (Canagliflozin) on Gastrointestinal Glucose Absorption and Metabolism in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Canagliflozin
Pharmacodynamic
Glucose absorption
Glucose metabolism
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2010-08-02
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: The purpose of this study is to evaluate the effect of canagliflozin on gastrointestinal glucose absorption in healthy volunteers.

Detailed description: This is a single center study that will be conducted in two Parts (Part 1 and Part 2) to evaluate the effect of a single-dose of canagliflozin on the absorption of glucose in healthy volunteers. Part 1 is a pilot (small) study where responses to key pharmocodynamic (PD) parameters (ie, specific tests on blood samples to evaluate effects of no treatment on the body) will be measured to confirm the study design and number of volunteers planned for Part 2. Part 2 is the main study where volunteers will be randomized (assigned to study drug or placebo by chance) to receive double-blind (neither the volunteer or study physician will know the identity of the treatment assigned) treatment with canagliflozin or placebo (treatment identical in appearance to canagliflozin but contains no active drug) to evaluate the effect of canagliflozin compared to placebo on gastrointestinal glucose absorption using a radiolabeled glucose tracer approach (ie, where a radioactive substance is combined with glucose allowing the movement of glucose in the body to be traced or detected). Blood and urine samples will be collected from volunteers at pre-defined times during the study for PD analysis. Safety will be monitored during the study by evaluating adverse events and results from clinical laboratory tests, vital signs measurements, electrocardiograms (ECGs), and physical examinations performed. Volunteers in Part 1 will receive 240 ml of water 10 minutes before starting of the MMTT in each period (Periods 1 and 2). Volunteers in Part 2 will receive study drug 20 minutes prior to starting of the MMTT in treatment sequence 1 (a single 300-mg dose of canagliflozin in Period 1 followed by matching placebo in Period 2) or in treatment Sequence 2 (matching placebo in Period 1 followed by a single 300-mg dose of canagliflozin in Period 2). Periods 1 and 2 will be separated by 7 to 21 days.

Eligibility criteria: Inclusion Criteria:

* Have a Body Mass Index (BMI) between 20 and 27 kg/m2 (inclusive) and a body weight not less than 50 kg
* Be healthy on the basis of physical examination including medical history, vital signs, 12-lead ECG, and all other screening lab tests performed at Screening and Admission
* Agree (if men) to use a double barrier method of birth control (e.g., condom for them and use of spermacide with diaphragm, hormonal contraceptives or intrauterine devices by female partner) during the study and for three months following the last dose of study medication, and to not donate sperm during the study and for 3 months after receiving the last dose of study medication
* Willing/able to adhere to the prohibitions and restrictions specified in this protocol
* Must have signed an informed consent form.

Exclusion Criteria:

* Have a history of, or currently active, illness or medical condition or disorder that the Investigator considers to be clinically significant
* Has been a smoker or tobacco user within the past 6 months
* Have a history of recent major surgery (within 6 months of study start)
* Tested positive for serology: hepatitis B surface antigen (HBsAg), hepatitis C antibodies (anti-HCV) or human immunodeficiency virus (HIV) antibodies
* Fasting plasma glucose \> 110 mg/dL
* Have a history of alcohol or drug abuse within 2 years prior to Screening or a positive test for alcohol and/or drugs of abuse (including but not limited to barbiturates, opiates, cocaine, cannabinoids, amphetamines,MDMA (Ecstasy) and benzodiazepines) at Screening

Primary outcomes:
measure: The amount of ingested glucose that is absorbed in systemic circulation
timeFrame: During the first 1 and 2 hours after a standard mixed meal
Secondary outcomes:
measure: The amount of ingested glucose that is absorbed in systemic circulation
timeFrame: 2-6 hr and 0-6 hr after a standard mixed meal
measure: Endogenous glucose production (EGP)
timeFrame: At protocol-specified time points after a standard mixed meal
measure: Total and incremental plasma glucose and insulin area under the curve (AUC)
timeFrame: 0-1, 0-2, 2-6, and 0-6 hours after a standard mixed meal
measure: Gastric emptying: peak level, time to peak level, and AUCs
timeFrame: 0-6 hours after a standard mixed meal
measure: Rate of Peripheral glucose disposal (Rd)
timeFrame: At protocol-specified time points after a standard mixed meal
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Polidori D, Sha S, Mudaliar S, Ciaraldi TP, Ghosh A, Vaccaro N, Farrell K, Rothenberg P, Henry RR. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care. 2013 Aug;36(8):2154-61. doi: 10.2337/dc12-2391. Epub 2013 Feb 14.