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

Primary Purpose

Diabetes Mellitus, Type 2

Status

Terminated

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

JNJ-64565111

Placebo

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Cohort 1 (JNJ-64565111 2.5 nmol/kg or Placebo)

Cohort 2 (JNJ-64565111 3 nmol/kg or Placebo)

Cohort 3 (JNJ-64565111 3.5 nmol/kg or Placebo)

Cohort 4 (JNJ-64565111 Repeat or Lower Dose or Placebo)

Arm Description

Participants in ratio of 3:1 will receive 2.5 Nanomole Per Kilogram (nmol/kg) JNJ-64565111 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.

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.

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.

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events as a Measure of Safety and Tolerability

Secondary Outcome Measures

Number of Participants With Incidence of Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity

Change From Baseline in Body Weight

Maximum Observed Plasma Concentration (Cmax)

Maximum observed plasma concentration (Cmax) will be assessed after first dose and last dose.

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.

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.

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.

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.

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.

Apparent Volume of Distribution (V/F)

Apparent volume of distribution will be assessed after first dose and last dose.

Terminal Rate Constant (K)

Terminal rate constant will be assessed after first dose and last dose.

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.

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.

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.

Accumulation Ratio

Accumulation ratio calculated as AUC(0-tau), Day 22 / AUC(0-tau), Day 1 will be assessed after last dose.

Change From Baseline in Blood Pressure

Change From Baseline in Heart Rate

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.

Change From Baseline in Fasting Plasma Glucose (FPG)

Change From Baseline in Hemoglobin A1c (HbA1c)

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.

Change From Baseline in Insulin Secretion

Change From Baseline in Insulin Sensitivity

Change From Baseline for C-peptide

Change From Baseline for Glucagon

Full Information

NCT ID

NCT02862431

First Posted

June 24, 2016

Last Updated

June 30, 2023

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT02862431

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Terminated

Why Stopped

manufacturing-related issues

Study Start Date

July 12, 2016 (Actual)

Primary Completion Date

November 29, 2016 (Actual)

Study Completion Date

December 5, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1 (JNJ-64565111 2.5 nmol/kg or Placebo)

Arm Type

Experimental

Arm Description

Participants in ratio of 3:1 will receive 2.5 Nanomole Per Kilogram (nmol/kg) JNJ-64565111 or placebo.

Arm Title

Cohort 2 (JNJ-64565111 3 nmol/kg or Placebo)

Arm Type

Experimental

Arm Description

Arm Title

Cohort 3 (JNJ-64565111 3.5 nmol/kg or Placebo)

Arm Type

Experimental

Arm Description

Arm Title

Cohort 4 (JNJ-64565111 Repeat or Lower Dose or Placebo)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

JNJ-64565111

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Participants will receive Placebo subcutaneously in the abdomen on Days 1, 8, 15 and 22.

Primary Outcome Measure Information:

Title

Number of Participants With Adverse Events as a Measure of Safety and Tolerability

Time Frame

Up to Day 72

Secondary Outcome Measure Information:

Title

Number of Participants With Incidence of Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity

Time Frame

Up to Day 72

Title

Change From Baseline in Body Weight

Time Frame

Baseline, up to Day 72

Title

Maximum Observed Plasma Concentration (Cmax)

Description

Maximum observed plasma concentration (Cmax) will be assessed after first dose and last dose.

Time Frame

Up to Day 72

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Description

Tmax defined as actual sampling time to reach maximum observed analyte concentration will be assessed after first dose and last dose.

Time Frame

Up to Day 72

Title

Area Under Concentration from time zero to the last quantifiable concentration AUC(0-last)

Description

AUC from time zero to the last quantifiable concentration will be assessed after first dose and after last dose.

Time Frame

Up to Day 72

Title

Area Under Curve over the dosing interval AUC(0-tau)

Description

Time Frame

Up to Day 72

Title

Elimination Half-Life (t1/2)

Description

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.

Time Frame

Up to Day 72

Title

Apparent Clearance (CL/F)

Description

The Oral Clearance (CL/F) is the clearance based on oral bioavailability. CL/F will be assessed after first dose and last dose.

Time Frame

Up to Day 72

Title

Apparent Volume of Distribution (V/F)

Description

Apparent volume of distribution will be assessed after first dose and last dose.

Time Frame

Up to Day 72

Title

Terminal Rate Constant (K)

Description

Terminal rate constant will be assessed after first dose and last dose.

Time Frame

Up to Day 72

Title

Average concentration over the dosing interval at steady state (Caverage,ss)

Description

The average concentration over the dosing interval at steady state, calculated as AUC(0-tau)/tau and will be assessed after last dose.

Time Frame

Up to Day 72

Title

Minimum Observed Plasma Concentration (Cmin)

Description

The Cmin is the minimum observed plasma concentration over the dosing interval at steady state. Cmin will be assessed after last dose.

Time Frame

Up to Day 72

Title

Area Under Curve from time zero extrapolated to infinity AUC(0-inf)

Description

AUC from time zero extrapolated to infinity will be assessed after last dose.

Time Frame

Up to Day 72

Title

Accumulation Ratio

Description

Accumulation ratio calculated as AUC(0-tau), Day 22 / AUC(0-tau), Day 1 will be assessed after last dose.

Time Frame

Up to Day 72

Title

Change From Baseline in Blood Pressure

Time Frame

Baseline, up to Day 72

Title

Change From Baseline in Heart Rate

Time Frame

Baseline, up to Day 72

Title

Change From Baseline for 24-hour Mean Plasma Glucose

Description

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.

Time Frame

Baseline, Day 26

Title

Change From Baseline in Fasting Plasma Glucose (FPG)

Time Frame

Baseline, up to Day 72

Title

Change From Baseline in Hemoglobin A1c (HbA1c)

Time Frame

Baseline, up to Day 72

Title

Change From Baseline on Fasting Lipids

Description

Time Frame

Baseline, up to Day 72

Title

Change From Baseline in Insulin Secretion

Time Frame

Baseline, Day 26

Title

Change From Baseline in Insulin Sensitivity

Time Frame

Baseline, Day 26

Title

Change From Baseline for C-peptide

Time Frame

Baseline, Day 26

Title

Change From Baseline for Glucagon

Time Frame

Baseline, Day 26

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

City

Neuss

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

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

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