Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-64565111 in Type 2 Diabetes Mellitus (T2DM)

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Double-Blind, Randomized, Placebo-Controlled, Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-64565111 in Men and Women With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02862431
• Other study ID #: CR108166
• Secondary ID: 64565111EDI10012
• Status: Terminated
• Phase: Phase 1
• Start date: July 12, 2016
• Est. completion date: December 5, 2016

Study information

• Verified date: June 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and tolerability of JNJ-64565111 in adult Men and Women (of non-child bearing potential) with Type 2 Diabetes Mellitus.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: December 5, 2016
• Est. primary completion date: November 29, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Diagnosis of Type 2 Diabetes Mellitus (T2DM) at least 3 months prior to Screening

• On a stable treatment regimen at least 3 months prior to Screening of (1) diet and exercise, or (2) metformin monotherapy (at a dose of at least 1,000 milligram (mg) per day)

• Blood pressure between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and between 60 and 100 mmHg diastolic, inclusive at Screening (sitting) and Day -2 (supine). If blood pressure is out of range, up to 2 repeated assessments are permitted

• HbA1c greater than or equal to 6.5% and less than 8.5% at Screening

• Females of non-childbearing potential

Exclusion Criteria:

• History of, or currently active, significant illness or medical disorders, including cardiovascular disease (including cardiac arrhythmias, myocardial infarction, stroke, peripheral vascular disease), hematological disease (example, von Willebrand's disease or other bleeding disorders), respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmologic disorders, neoplastic disease, skin disorder, renal disorder, or any other illness that the Principal Investigator (PI) considers should exclude the participant or that could interfere with the interpretation of the study results

• Previous surgical treatment for obesity (example, gastric bypass, gastric banding)

• History of diabetic neuropathy with signs of gastroparesis and/or known proliferative retinopathy or maculopathy

• History or current diagnosis of acute or chronic pancreatitis

• History of an invasive cardiovascular surgical procedure including, but not limited to, coronary artery bypass graft (CABG), or percutaneous coronary intervention (PCI)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• JNJ-64565111
Participants will receive JNJ-64565111 subcutaneously in the abdomen on Days 1, 8, 15 and 22.
• Placebo
Participants will receive Placebo subcutaneously in the abdomen on Days 1, 8, 15 and 22.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events as a Measure of Safety and Tolerability		Up to Day 72
Secondary	Number of Participants With Incidence of Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity		Up to Day 72
Secondary	Change From Baseline in Body Weight		Baseline, up to Day 72
Secondary	Maximum Observed Plasma Concentration (Cmax)	Maximum observed plasma concentration (Cmax) will be assessed after first dose and last dose.	Up to Day 72
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)	Tmax defined as actual sampling time to reach maximum observed analyte concentration will be assessed after first dose and last dose.	Up to Day 72
Secondary	Area Under Concentration from time zero to the last quantifiable concentration AUC(0-last)	AUC from time zero to the last quantifiable concentration will be assessed after first dose and after last dose.	Up to Day 72
Secondary	Area Under Curve over the dosing interval AUC(0-tau)	The AUC [0-tau] is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption. AUC [0-tau] will be assessed after first dose and last dose.	Up to Day 72
Secondary	Elimination Half-Life (t1/2)	The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. t1/2 will be assessed after first dose and last dose.	Up to Day 72
Secondary	Apparent Clearance (CL/F)	The Oral Clearance (CL/F) is the clearance based on oral bioavailability. CL/F will be assessed after first dose and last dose.	Up to Day 72
Secondary	Apparent Volume of Distribution (V/F)	Apparent volume of distribution will be assessed after first dose and last dose.	Up to Day 72
Secondary	Terminal Rate Constant (K)	Terminal rate constant will be assessed after first dose and last dose.	Up to Day 72
Secondary	Average concentration over the dosing interval at steady state (Caverage,ss)	The average concentration over the dosing interval at steady state, calculated as AUC(0-tau)/tau and will be assessed after last dose.	Up to Day 72
Secondary	Minimum Observed Plasma Concentration (Cmin)	The Cmin is the minimum observed plasma concentration over the dosing interval at steady state. Cmin will be assessed after last dose.	Up to Day 72
Secondary	Area Under Curve from time zero extrapolated to infinity AUC(0-inf)	AUC from time zero extrapolated to infinity will be assessed after last dose.	Up to Day 72
Secondary	Accumulation Ratio	Accumulation ratio calculated as AUC(0-tau), Day 22 / AUC(0-tau), Day 1 will be assessed after last dose.	Up to Day 72
Secondary	Change From Baseline in Blood Pressure		Baseline, up to Day 72
Secondary	Change From Baseline in Heart Rate		Baseline, up to Day 72
Secondary	Change From Baseline for 24-hour Mean Plasma Glucose	Mean plasma glucose defined as the total and/or incremental area under the concentration (AUC) time curve over 0 to 24 hours, divided by 24.	Baseline, Day 26
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG)		Baseline, up to Day 72
Secondary	Change From Baseline in Hemoglobin A1c (HbA1c)		Baseline, up to Day 72
Secondary	Change From Baseline on Fasting Lipids	Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides and free fatty acids will be reported.	Baseline, up to Day 72
Secondary	Change From Baseline in Insulin Secretion		Baseline, Day 26
Secondary	Change From Baseline in Insulin Sensitivity		Baseline, Day 26
Secondary	Change From Baseline for C-peptide		Baseline, Day 26
Secondary	Change From Baseline for Glucagon		Baseline, Day 26