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

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

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.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: JNJ-64565111; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (JNJ-64565111 2.5 nmol/kg or Placebo); Participants in ratio of 3:1 will receive 2.5 Nanomole Per Kilogram (nmol/kg) JNJ-64565111 or placebo.	Drug: JNJ-64565111; Participants will receive JNJ-64565111 subcutaneously in the abdomen on Days 1, 8, 15 and 22.; Drug: Placebo; Participants will receive Placebo subcutaneously in the abdomen on Days 1, 8, 15 and 22.
Experimental: Cohort 2 (JNJ-64565111 3 nmol/kg or Placebo); Participants in ratio of 3:1 will receive 3.0 nmol/kg JNJ-64565111 or placebo. Dose may be escalated based on review by Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29 but dose will not exceed 3.5 nmol/kg.	Drug: JNJ-64565111; Participants will receive JNJ-64565111 subcutaneously in the abdomen on Days 1, 8, 15 and 22.; Drug: Placebo; Participants will receive Placebo subcutaneously in the abdomen on Days 1, 8, 15 and 22.
Experimental: Cohort 3 (JNJ-64565111 3.5 nmol/kg or Placebo); Participants in ratio of 3:1 will receive 3.5 nmol/kg JNJ-64565111 or placebo. Dose may be escalated based on review by Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29 but dose will not exceed 3.5 nmol/kg.	Drug: JNJ-64565111; Participants will receive JNJ-64565111 subcutaneously in the abdomen on Days 1, 8, 15 and 22.; Drug: Placebo; Participants will receive Placebo subcutaneously in the abdomen on Days 1, 8, 15 and 22.
Experimental: Cohort 4 (JNJ-64565111 Repeat or Lower Dose or Placebo); Participants in ratio of 3:1 will receive a dose of JNJ-64565111 or placebo that would be a repeat or lower dose level previously assessed as well-tolerated.	Drug: JNJ-64565111; Participants will receive JNJ-64565111 subcutaneously in the abdomen on Days 1, 8, 15 and 22.; Drug: Placebo; Participants will receive Placebo subcutaneously in the abdomen on Days 1, 8, 15 and 22.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Up to Day 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Incidence of Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity		Up to Day 72
Change From Baseline in Body Weight		Baseline, up to Day 72
Maximum Observed Plasma Concentration (Cmax)	Maximum observed plasma concentration (Cmax) will be assessed after first dose and last dose.	Up to Day 72
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
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
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
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
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
Apparent Volume of Distribution (V/F)	Apparent volume of distribution will be assessed after first dose and last dose.	Up to Day 72
Terminal Rate Constant (K)	Terminal rate constant will be assessed after first dose and last dose.	Up to Day 72
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
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
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
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
Change From Baseline in Blood Pressure		Baseline, up to Day 72
Change From Baseline in Heart Rate		Baseline, up to Day 72
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
Change From Baseline in Fasting Plasma Glucose (FPG)		Baseline, up to Day 72
Change From Baseline in Hemoglobin A1c (HbA1c)		Baseline, up to Day 72
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
Change From Baseline in Insulin Secretion		Baseline, Day 26
Change From Baseline in Insulin Sensitivity		Baseline, Day 26
Change From Baseline for C-peptide		Baseline, Day 26
Change From Baseline for Glucagon		Baseline, Day 26

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2016
• Primary Completion (Actual): November 29, 2016
• Study Completion (Actual): December 5, 2016

Study Registration Dates

• First Submitted: June 24, 2016
• First Submitted That Met QC Criteria: August 9, 2016
• First Posted (Estimated): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: CR108166; 64565111EDI1001 (Other Identifier: Janssen Research & Development, LLC); 2016-001084-37 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No