A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of JNJ-38431055 in Volunteers With Type 2 Diabetes Mellitus

Phase 1

Terminated

• Conditions: Diabetes Mellitus, Type 2

• Registration Number: NCT00946972
• Lead Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Brief Summary

This study will assess the safety, tolerability, pharmacokinetics (explores what the body does to the drug), and pharmacodynamics (explores what a drug does to the body) of multiple doses of JNJ-38431055 in volunteers with type 2 diabetes mellitus.

Detailed Description

This is a double-blind (neither physician or participant knows the name of the assigned study drug), placebo-controlled (substance containing no medication), study in male and female volunteers with type 2 diabetes mellitus. For each volunteer, the study consists of a screening phase (up to 45 days), a run-in phase during which volunteers discontinue their oral anti-hyperglycemic drugs (21 to 35 days), a treatment phase during which volunteers will continue to be off their anti-hyperglycemic drugs and receive daily study drug (JNJ-38431055 or placebo) for 14 days, and a follow-up phase (10 days). After the follow-up phase, volunteers will restart their oral anti-hyperglycemic drugs. The following safety evaluations will be taken throughout the study: Electrocardiogram (an ECG is a painless procedure that gives a picture of the electrical activity of the heart), blood pressure, heart rate, and blood samples for laboratory tests. The primary outcomes will be safety and tolerability of JNJ-38431055 and 24-hour weighted mean glucose concentrations after 14 days of dosing with JNJ-38431055. Study drug will be administered as daily doses for 14 days. The two treatments will be JNJ-38431055 and placebo.

Study Timeline

• Study Start: 2009-07
• Study First Submitted: 2009-07-23
• Study First Submitted QC: 2009-07-23
• Study First Posted: 2009-07-27
• Study Completion: 2009-11
• Status Verified: 2010-03
• Last Update Submitted: 2010-03-04
• Last Update Posted: 2010-03-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

• Males or postmenopausal or surgically sterilized females, who have type 2 diabetes mellitus
• Medically stable on the basis of physical examination, medical history, laboratory safety test results, vital signs and ECG performed at screening
• Body Mass Index (BMI) between 22 and 39.9 kg/m2, inclusive
• On a generally stable antihyperglycemic agent regimen (i.e. with no change in medication, or only 1 dose step change in dose) for at least 2 months prior to Screening visit, including volunteers who are: (a) Not currently on antihyperglycemic therapy and have an HbA1c >=7.0 % and <=10%, or (b) On a single oral antihyperglycemic agent [metformin, a sunfonylurea, a meglitinide (e.g., repaglininide or nateglinide), a DPP-IV inhibitor (sitagliptin or vildagliptin), or an alpha-glucosidase inhibitor (e.g., acarbose)] and have an HbA1c >=6.5% and <=9.5%, or (c) On low-dose dual oral agent therapy (i.e., <50% maximum labeled doses of both agents) and have an HbA1c >=6.5% and <=9.5%
• On Day -2 (two days prior to study drug administration), FPG concentrations between 120 mg/dL and 260 mg/dL, inclusive

Exclusion Criteria

• Taking non-oral antihyperglycemic agent (e.g., insulin, exenatide or other GLP-1 analogues), or taking a thiazolidinedione (i.e., a PPARg agonist) within 3 months of the Screening visit
• History of a recent severe hypoglycemic episode, recurrent hypoglycemic episodes (i.e., within the past year), or a history of hypoglycemic unawareness
• History of clinically significant diabetic complications, including retinopathy, nephropathy, neuropathy or gastroparesis
• Positive test for alcohol and/or drugs of abuse
• Psychological and/or emotional problems, which would render the informed consent invalid, or limit the ability of the volunteer to comply with the study requirements
• Any condition that, in the opinion of the investigator, would compromise the well being of the volunteer or the study or prevent the volunteer from meeting or performing study requirements

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Adverse events, laboratory values, vital signs, ECGs	Throughout the study

Secondary Outcome Measures

Name	Time	Method
24 hour weighted mean glucose	24 hours
Fasting plasma glucose, glycosylated albumin	14 days
Dose response	14 days
Measures of beta-cell function	14 days
Incretin levels	14 days