A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of JNJ-28431754 in Patients With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00963768
First received: August 20, 2009
Last updated: April 22, 2014
Last verified: April 2014

August 20, 2009
April 22, 2014
June 2007
December 2007   (final data collection date for primary outcome measure)
The number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Up to 34 days (baseline [Day -1] through follow up [10 days following Day 22 visit]) ] [ Designated as safety issue: No ]
Safety and tolerability (adverse events including hypoglycemia, vital signs, 12 lead ECG, physical examination and laboratory tests [hematology, clinical chemistry, serum and urine electrolytes, renal function, urinary analysis, bone biomarkers]) [ Time Frame: From baseline (Day -1) through follow up (10 days following Day 22 visit) ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00963768 on ClinicalTrials.gov Archive Site
  • Change from baseline (Day -1) for mean 24-hour plasma glucose concentration [ Time Frame: Day -1 through Day 16 ] [ Designated as safety issue: No ]
  • Change from baseline 24-hour urinary glucose excretion (UGE) [ Time Frame: Day -1 through 16 ] [ Designated as safety issue: No ]
  • Change from baseline mean fasting plasma glucose [ Time Frame: Day -1 through Day 16 ] [ Designated as safety issue: No ]
  • Change from baseline mean morning fasting body weight [ Time Frame: Day -1 through 20 ] [ Designated as safety issue: No ]
  • Renal glucose threshold [ Time Frame: Day -1 through Day 16 ] [ Designated as safety issue: No ]
  • Change from baseline (Day -1) for mean 24-hour plasma glucose concentration [ Time Frame: Day 1 and 16 ] [ Designated as safety issue: No ]
  • Change from baseline 24-hour urinary glucose excretion (UGE) [ Time Frame: Day 1 through 16 ] [ Designated as safety issue: No ]
  • Change from baseline mean fasting plasma glucose [ Time Frame: Day 1 and 16 ] [ Designated as safety issue: No ]
  • Change from baseline mean morning fasting body weight [ Time Frame: Day 1 through 20 ] [ Designated as safety issue: No ]
  • Renal glucose threshold [ Time Frame: Day -1, 1 and 16 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of JNJ-28431754 in Patients With Type 2 Diabetes Mellitus
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

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Diabetes Mellitus, Type 2
  • Drug: JNJ 28431754
    A liquid suspension of 30 mg, 100 mg, 300 mg of JNJ-28431754 taken once (or twice) daily or 600 mg taken once daily will be administered by study personnel directly into the patient's mouth using an oral liquid dispenser for 14 days (Day 1 and Days 3 through 16).
    Other Name: Canagliflozin
  • Drug: Placebo
    A liquid suspension of placebo will be administered by study personnel directly into the patient's mouth using an oral liquid dispenser once or twice daily for 14 days (Day 1 and Days 3 through 16).
    Other Name: Placebo
  • Experimental: Cohort 1
    JNJ-28431754 30 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts.
    Interventions:
    • Drug: JNJ 28431754
    • Drug: Placebo
  • Experimental: Cohort 2
    JNJ-28431754 100 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts.
    Interventions:
    • Drug: JNJ 28431754
    • Drug: Placebo
  • Experimental: Cohort 3
    JNJ-28431754 300 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts.
    Interventions:
    • Drug: JNJ 28431754
    • Drug: Placebo
  • Experimental: Cohort 4
    JNJ-28431754 600 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts.
    Interventions:
    • Drug: JNJ 28431754
    • Drug: Placebo
  • Experimental: Cohort 5
    JNJ-28431754 at 30 mg/day, 100 mg/day, or 300 mg/day or placebo (the dose level to be determined from the prior cohort of patients tested and considered to be well tolerated).
    Interventions:
    • Drug: JNJ 28431754
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
116
December 2007
December 2007   (final data collection date for primary outcome measure)

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
Both
25 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany,   Korea, Republic of
 
NCT00963768
CR012451, 28431754NAP1002
No
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Not Provided
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP