A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of JNJ-28431754 in Patients With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Placebo; JNJ 28431754 300 mg/placebo; JNJ 28431754 100 mg/placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): one placebo capsule once daily for 3 days immediately prior to randomization to double-blind treatment with JNJ 28431754 or placebo; one 300-mg capsule of JNJ-28431754 or placebo twice-daily for 4 weeks; one 100-mg capsule of JNJ-28431754 or placebo once-daily for 4 weeks
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Type 2 diabetes mellitus; Canagliflozin; JNJ-28431754; Insulin; Pharmacokinetic; Pharmacodynamic; SGLT-1