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

Johnson & Johnson (J&J)

Status and phase: Completed; Phase 1

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: JNJ-38431055 Dose 2; Drug: Placebo; Drug: JNJ-38431055 Dose 1; Drug: Sitagliptin 100 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00871507

CR016048

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 25 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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25 participants in 4 patient groups, including a placebo group

001

Experimental group

Treatment:

Drug: JNJ-38431055 Dose 1

002

Experimental group

Treatment:

Drug: JNJ-38431055 Dose 2

003

Placebo Comparator group

Treatment:

Drug: Placebo

004

Active Comparator group

Treatment:

Drug: Sitagliptin 100 mg