A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of JNJ-28431754 in Patients With Type 2 Diabetes Mellitus
A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of JNJ-28431754 in Patients With Type 2 Diabetes Mellitus
The purpose of this study is to evaluate the safety, tolerability, pharmacodynamic effects
 and pharmacokinetic characteristics of JNJ-28431754 after multiple dosing in patients with
 Type 2 Diabetes Mellitus who are on a stable dose of insulin.
This is a randomized (study drug assigned by chance), double-blind (neither the patient or
 the study doctor will know the name of the assigned treatment), parallel-group (each group of
 patients will be treated at the same time) to determine the safety, tolerability,
 pharmacokinetics (PK) (how drugs are absorbed in the body, how they are distributed within
 the body and how they are removed from the body over time) and the pharmacodynamics (PD) (the
 action or effects a drug has on the body) of oral (taken by mouth) doses of JNJ 28431754
 taken once or twice daily compared to placebo (treatment identical in appearance to
 JNJ-2843174 but contains no active drug) in patients with Type 2 Diabetes Mellitus (T2DM) who
 are receiving therapy with a fixed-dose regimen of insulin. Two groups of 14 patients will be
 studied; one group will receive JNJ-2843174 (100 mg) or placebo once daily for 4 weeks and
 the other group will receive JNJ-2843174 (300 mg) or placebo twice daily for 4 weeks. In the
 3 days immediately prior to the beginning of the 4-week treatment period, all patients will
 take a single oral dose of placebo once daily and have blood and urine samples collected for
 laboratory testing. During the study, all patients will be allowed to continue on their
 normal medication regimen of insulin and other allowed anti-diabetic medications. On selected
 days during the study, patients will be required to stay overnight at the study center to
 have study drug administered and/or to have blood and urine samples collected for laboratory
 testing. During the study, if patients experience worsened glycemia (blood sugar), rescue
 therapy with additional insulin of the same type but at a higher dose may be initiated by the
 Investigator if medically appropriate. During the study, patients will be monitored for
 safety by review of adverse events and results from laboratory tests, 12-lead
 electrocardiograms (ECGs), vital signs measurements, body weight, physical examinations, and
 self-monitored blood glucose (SMGB) measurements. Unless otherwise specified, study drug will
 be taken orally (by mouth) after an overnight fast for at least 8 hours followed by a meal
 within 10 minutes; for twice daily dosing, the evening dose will be taken just prior to the
 evening meal (dinner). All patients will take one placebo capsule once daily for 3 days
 immediately prior to randomization. After randomization, patients will take JNJ-28431754 (100
 mg) or placebo once daily or JNJ-28431754 (300 mg) or placebo twice daily for 4 weeks.
Inclusion Criteria:

 -  Have been diagnosed with T2DM for at least 6 months prior to study screening

 -  Be on stable insulin regimens at the time of screening

 -  Have a stable weight (ie, no change more than 5% in the 3 months prior to screening)

 -  Have a glycosylated hemoglobin (A1C) of >=7% and <=10.5% at study screening

 Exclusion Criteria:

 -  Have history of Type 1 diabetes mellitus, secondary forms of diabetes, diabetic
 ketoacidosis, pancreas or beta cell transplantation

 -  Have a known history of more than 2 severe hypoglycemic episodes as defined by the
 protocol within the past year

 -  Have history of, or currently active, significant illness as determined by the
 Investigator