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

NCT ID: NCT00963768

Last Updated: 2014-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2007-12-31

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

JNJ 28431754

Intervention Type: DRUG

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).

Placebo

Intervention Type: DRUG

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).

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.

Group Type: EXPERIMENTAL

JNJ 28431754

Intervention Type: DRUG

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).

Placebo

Intervention Type: DRUG

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).

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.

Group Type: EXPERIMENTAL

JNJ 28431754

Intervention Type: DRUG

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).

Placebo

Intervention Type: DRUG

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).

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.

Group Type: EXPERIMENTAL

JNJ 28431754

Intervention Type: DRUG

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).

Placebo

Intervention Type: DRUG

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).

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).

Group Type: EXPERIMENTAL

JNJ 28431754

Intervention Type: DRUG

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).

Placebo

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Canagliflozin

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

Role: STUDY_DIRECTOR

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Locations

Chula Vista, California, United States

Neuss, , Germany

Seoul, , South Korea

Countries

United States; Germany; South Korea

References

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.

Reference Type: DERIVED

PMID: 25268802 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25166023 (View on PubMed)

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=747&filename=CR012451_CSR.pdf

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

Other Identifiers

28431754NAP1002

Identifier Type: OTHER

Identifier Source: secondary_id

CR012451

Identifier Type: -

Identifier Source: org_study_id