Clinical trial NCT00871507: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (Explores What the Body Does to the Drug), and Pharmacodynamics (Explores What a Drug Does to the Body) of JNJ-38431055 in Volunteers With Type 2 Diabetes Mellitus
Official title: SD in Subjects With T2DM
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes Mellitus, Type 2
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2009-03-30
Enrollment: 25
Sex: ALL
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 JNJ-38431055 in volunteers with type 2 diabetes mellitus.

Detailed description: This is a double-blind (neither physician or participant knows name of the assigned study drug), placebo-controlled (substance containing no medication), crossover 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 hypoglycemic drugs (28 days), a treatment phase during which volunteers will continue to be off their oral hypoglycemic drugs (28 days) and will receive 4 single dose study treatments in a randomized (study sequence assigned by chance) sequence, and a follow-up phase (10 days). After the follow-up phase volunteers will restart their oral hypoglycemic drugs. During the treatment phase there will be at least 7 days between each of the 4 treatments. The four treatments will be Dose 1 of JNJ-38431055, Dose 2 of JNJ-38431055, sitagliptin (Januvia), and placebo. 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 outcome will be incremental glucose after an oral glucose tolerance test. Study drug will be administered as single oral doses separated by at least 7 days. The four treatments will be Dose 1 of JNJ-38431055, Dose 2 of JNJ-38431055, sitagliptin (Januvia), and placebo.

Eligibility criteria: 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 the Screening Visit, including volunteers who are:(a) Not currently on antihyperglycemic therapy and have an HbA1c =7.0% and =10.0%, or (b) On a single oral antihyperglycemic agent \[metformin, a sulfonylurea, a meglitinide (e.g., repaglininide or nateglinide), a DPP-4 inhibitor (sitagliptin or vildagliptin), or an alpha-glucosidase inhibitor (e.g., acarbose)\] 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 -1, 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 Day -1
* 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.

Primary outcomes:
measure: Incremental glucose AUC after an oral glucose tolerance test (OGTT)
timeFrame: 0-4 hours after OGTT
Secondary outcomes:
measure: Incremental glucose AUC after a meal tolerance test (MTT)
timeFrame: 0-4 hours after MTT
measure: Measurements of beta-cell function
timeFrame: 0-4 hours after OGTT/MTT
measure: Effect on incretin levels
timeFrame: 0-4 hours after OGTT
measure: Pharmacokinetics
timeFrame: 48 hours after dosing
measure: Safety and Tolerability
timeFrame: Throughout study
Other outcomes:
Locations:
city: Fort Myers
country: United States
state: Florida
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References: