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
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: JNJ 28431754
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 116
Study Start Date: June 2007
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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.
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 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.
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 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.
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 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).
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

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

Ages Eligible for Study:   25 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00963768

Locations
United States, California
Chula Vista, California, United States
Germany
Neuss, Germany
Korea, Republic of
Seoul, Korea, Republic of
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00963768     History of Changes
Other Study ID Numbers: CR012451, 28431754NAP1002
Study First Received: August 20, 2009
Last Updated: April 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Diabetes Mellitus, Type 2
JNJ-28431754
Canagliflozin
Sodium Glucose Co-transporter (SGLT2 inhibitor)
Pharmacokinetics
Pharmacodynamics

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 16, 2014