Clinical trial NCT00963768: A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of JNJ-28431754 in Patients With Type 2 Diabetes Mellitus
Official title: A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Oral Doses of JNJ-28431754 in Type 2 Diabetes Mellitus Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes Mellitus, Type 2
JNJ-28431754
Canagliflozin
Sodium Glucose Co-transporter (SGLT2 inhibitor)
Pharmacokinetics
Pharmacodynamics
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2009-08-24
Enrollment: 116
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (ie, blood levels of JNJ-28431754) and pharmacodynamics (ie, urine and blood levels of glucose) of JNJ-28431754 compared to placebo in patients with Type 2 diabetes mellitus.

Detailed description: This is a randomized (study drug assigned by chance), double-blind (neither physician, patient nor the sponsor knows the assigned treatment), placebo-controlled, single and multiple (14 days) ascending dose, parallel group study in 3 study centers (United States, Germany and South Korea). Five cohorts (groups) of patients with Type 2 diabetes mellitus (T2DM) will be studied. One dose level will be evaluated in each cohort. Sixteen (16) patients will be randomly assigned to receive JNJ-28431754 and four (4) patients to receive matching placebo within each cohort. The planned doses are 30, 100, 300 and 600 mg per day. Twice-daily dosing may also be evaluated in one or more of the cohorts. An additional cohort of Asian patients will also be evaluated at a dose level, which was previously tested in a prior cohort and considered to be well tolerated. Blood and urine samples will be collected from patients during the study for pharmacokinetic and pharmacodynamic assessments. The safety and tolerability of JNJ-28431754 will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Patients must have been diagnosed with Type 2 Diabetes for at least one year before screening
* Patients must be taking a stable dose of oral (by mouth) anti-diabetic monotherapy or a combination of two anti-diabetic medications
* Males or postmenopausal or surgically sterile women (post-menopausal is defined as no menses for at least 18 months prior to study start or no menses for 6 to 18 months)
* Body mass index (weight in kg/height in m2) should be between 20 to 39.9 kg/m2

Exclusion Criteria:

* History of Type 1, brittle diabetes or secondary forms of diabetes
* History of repeated severe hypoglycemic episodes
* History of diabetic complications including retinopathy, nephropathy, neuropathy, gastroparesis, or ketoacidosis
* History of, or currently active illness including but not limited to cardiovascular disease, hematological disease, respiratory disease, hepatic or gastrointestinal disease, endocrine/metabolic disorders, neurologic or psychiatric disease, or malignant neoplasms considered by the Investigator to be clinically significant

Primary outcomes:
measure: The number of patients with adverse events as a measure of safety and tolerability
timeFrame: Up to 34 days (baseline [Day -1] through follow up [10 days following Day 22 visit])
Secondary outcomes:
measure: Change from baseline (Day -1) for mean 24-hour plasma glucose concentration
timeFrame: Day -1 through Day 16
measure: Change from baseline 24-hour urinary glucose excretion (UGE)
timeFrame: Day -1 through 16
measure: Change from baseline mean fasting plasma glucose
timeFrame: Day -1 through Day 16
measure: Change from baseline mean morning fasting body weight
timeFrame: Day -1 through 20
measure: Renal glucose threshold
timeFrame: Day -1 through Day 16
Other outcomes:
Locations:
city: Chula Vista
country: United States
state: California
city: Neuss
country: Germany
city: Seoul
country: Korea, Republic of
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: Sha S, Devineni D, Ghosh A, Polidori D, Hompesch M, Arnolds S, Morrow L, Spitzer H, Demarest K, Rothenberg P. Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with type 2 diabetes. PLoS One. 2014 Sep 30;9(9):e110069. doi: 10.1371/journal.pone.0110069. eCollection 2014.
citation: Sha S, Devineni D, Ghosh A, Polidori D, Hompesch M, Arnolds S, Morrow L, Spitzer H, Demarest K, Rothenberg P. Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with type 2 diabetes. PLoS One. 2014 Aug 28;9(8):e105638. doi: 10.1371/journal.pone.0105638. eCollection 2014.