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

Johnson & Johnson (J&J)

Status and phase: Completed; Phase 1

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Placebo; Drug: JNJ 28431754

Study type: Interventional

Funder types: Industry

Identifiers

NCT00963768

28431754NAP1002 (Other Identifier)

CR012451

Details and patient eligibility

About

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.

Full 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.

Enrollment: 116 patients

Sex: All

Ages: 25 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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116 participants in 5 patient groups

Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: JNJ 28431754

Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: JNJ 28431754

Cohort 3

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: JNJ 28431754

Cohort 4

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: JNJ 28431754

Cohort 5

Experimental group

Description:

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).

Treatment:

Drug: Placebo

Drug: JNJ 28431754