Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT01177163
First received: August 5, 2010
Last updated: May 27, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Placebo
Drug: JNJ 28431754 300 mg/placebo
Drug: JNJ 28431754 100 mg/placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-28431754 in Type-2 Diabetes Mellitus Subjects Not Optimally Controlled (A1C >=7.0%) on Fixed Doses of Insulin Therapy

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • The proportion of patients who need to decrease insulin dosage from prestudy dosage levels because of hypoglycemia [ Time Frame: From time of signed informed consent (Days -52 to -32) through to the end of the study (Days 34 to 39) or at the time of early withdrawal ] [ Designated as safety issue: No ]
  • The number of patients with specific treatment-emergent adverse events [ Time Frame: From time of signed informed consent (Days -52 to -32) through to the end of the study (Days 34 to 39) or at the time of early withdrawal ] [ Designated as safety issue: No ]
  • The number of patients with symptomatic hypoglycemia and severe hypoglycemia [ Time Frame: From time of signed informed consent (Days -52 to -32) through to the end of the study (Days 34 to 39) or at the time of early withdrawal ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma concentrations and pharmacokinetics parameters for JNJ 28431754 [ Time Frame: At protocol-specified timepoints from Day 1 (pre-dose) to Day 29 ] [ Designated as safety issue: No ]
  • Plasma glucose concentration-time profiles (pharmacodynamics parameter) [ Time Frame: At protocol specified timepoints on Day -1, Day 1, and Day 27 ] [ Designated as safety issue: No ]
  • Change in urine glucose excretion (pharmacodynamics parameter) [ Time Frame: At protocol specified timepoints on Day -1, Day 1, and Day 27 ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: May 2008
Study Completion Date: March 2009
Arms Assigned Interventions
001
Placebo one placebo capsule once daily for 3 days immediately prior to randomization to double-blind treatment with JNJ 28431754 or placebo
Drug: Placebo
one placebo capsule once daily for 3 days immediately prior to randomization to double-blind treatment with JNJ 28431754 or placebo
Experimental: 002
JNJ 28431754 100 mg/placebo one 100-mg capsule of JNJ-28431754 or placebo once-daily for 4 weeks
Drug: JNJ 28431754 100 mg/placebo
one 100-mg capsule of JNJ-28431754 or placebo once-daily for 4 weeks
Experimental: 003
JNJ 28431754 300 mg/placebo one 300-mg capsule of JNJ-28431754 or placebo twice-daily for 4 weeks
Drug: JNJ 28431754 300 mg/placebo
one 300-mg capsule of JNJ-28431754 or placebo twice-daily for 4 weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01177163

Locations
United States, California
Chula Vista, California, United States
United States, Texas
San Antonio, Texas, United States
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT01177163     History of Changes
Other Study ID Numbers: CR014881
Study First Received: August 5, 2010
Last Updated: May 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Type 2 diabetes mellitus
Canagliflozin
JNJ-28431754
Insulin
Pharmacokinetic
Pharmacodynamic
SGLT-1

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on November 20, 2014