- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03235219
A Phase 1b Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of JNJ-64565111 in Participants With Type 2 Diabetes Mellitus
April 13, 2023 updated by: Janssen Research & Development, LLC
A Double-Blind, Randomized, Placebo-Controlled, Multiple 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 Phase 1b 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
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
39
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Chula Vista, California, United States, 91911
- ProSciento, Inc.
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Florida
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Miami, Florida, United States, 33147
- Advanced Pharma CR, LLC
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 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
- Hemoglobin A1c (HbA1c) greater than or equal to (>=) 7.0 percent (%) and lesser than or equal to (<=)9.5% at Screening
- On a stable treatment regimen for at least 3 months prior to Screening of (1) diet and exercise, and/or (2) metformin monotherapy (at a dose of at least 1,000 milligram (mg) per day)
- Body mass index (BMI) ranging from 25 to 40 kilogram per square meter (kg/m^2) (inclusive), weighing between 75 and 130 kg (inclusive)
- A woman must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta- hCG) at Screening and Day -2
- Blood pressure (measured after the participant is sitting/ resting quietly for 5 minutes) 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 the average of the first triplicate blood pressure assessment is out of range, up to 2 repeated triplicate assessments are permitted
Exclusion Criteria:
- History or current diagnosis of acute or chronic pancreatitis
- Familial or personal history of multiple endocrine neoplasia type 2,familial/non-familial medullary thyroid carcinoma
- Donated blood or blood products or lost a significant amount of blood (>500 milliliter [mL]) within 3 months before the first administration of study drug
- History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening
- History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1 to 4: JNJ-64565111 or Placebo
Participants in cohort 1 to 4 in a ratio of 4:1 will receive a dose of JNJ-64565111 or placebo subcutaneously on Days 1, 8, 15 and 22. Cohort 1, 2 and 3 will be dosed in parallel.
Dosing for subsequent cohort 4 will be escalated based on review by the Sponsor and Principal Investigator of blinded safety, tolerability, pharmacokinetic, and (all available) pharmacodynamic data collected up to Day 29, but will not exceed from well-tolerated dose.
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Participants will receive JNJ-64565111 subcutaneously in the abdomen on Days 1, 8, 15 and 22.
Other Names:
Participants will receive placebo subcutaneously in the abdomen on Days 1, 8, 15 and 22.
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Experimental: Cohort 5: JNJ-64565111 (Repeat or Lower Dose) or Placebo
Participants in ratio of 4:1 will receive a dose of JNJ-64565111 or placebo subcutaneously on Days 1, 8, 15 and 22, and may be modified.
The dose can be repeated or lower than a dose previously assessed as well tolerated.
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Participants will receive JNJ-64565111 subcutaneously in the abdomen on Days 1, 8, 15 and 22.
Other Names:
Participants will receive placebo subcutaneously in the abdomen on Days 1, 8, 15 and 22.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time Frame: Up to Day 72
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An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
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Up to Day 72
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Serum Concentration (Cmax)
Time Frame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD.
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Maximum observed serum concentration (Cmax) of JNJ-64565111 will be assessed.
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First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD.
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Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Actual sampling time to reach maximum observed serum concentration (Tmax) of JNJ-64565111 will be assessed.
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First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Area Under Concentration-Time Curve From Time Zero to the Last Quantifiable Time (AUC [0-last])
Time Frame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD)
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The AUC (0-last) of JNJ-64565111 is the area under the serum concentration-time curve from time zero to last quantifiable time.
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First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD)
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Average Concentration Over the Dosing Interval Tau (T) at Steady State (Caverage,ss)
Time Frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Average concentration over the dosing interval tau at steady state of JNJ-64565111 (defined as area under the serum concentration time curve observed during a dosing interval (tau) at steady state) will be calculated as AUC(0- T)/T.
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Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Minimum Observed Serum Concentration (Cmin)
Time Frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Minimum observed serum concentration (Cmin) of JNJ-64565111 will be assessed.
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Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Accumulation Ratio
Time Frame: First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168 hours PD
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Accumulation ratio of JNJ-64565111, calculated as AUC(0-T), Day 22 / AUC(0-T), Day 1 will be assessed after last dose.
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First Dose: Predose (Day 1), and at 8, 24, 48, 72 and 120 hours post-dose (PD); Fourth Dose: predose (Day 22), and at 72, 96, 144, 168 hours PD
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Area Under Curve over the dosing interval AUC (0-T)
Time Frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168 hours PD
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The AUC (0-T) of JNJ-64565111 is the measure of the serum drug concentration from time zero to end of dosing interval.
It is used to characterize drug absorption.
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Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168 hours PD
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Apparent Terminal Elimination Half-life (t1/2term)
Time Frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Apparent terminal elimination half-life of JNJ-64565111, calculated as 0.693/apparent terminal elimination rate constant (Lambda[z]).
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Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Apparent Clearance (CL/F)
Time Frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Clearance obtained after subcutaneous (SC) dose (apparent SC clearance) is influenced by the fraction of the dose absorbed.
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
CL/F will be calculated as CL/F = Dose/AUC [0-infinity].
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Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Apparent Volume of Distribution (V/F)
Time Frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Apparent volume of distribution of JNJ-64565111 is based on the terminal phase following subcutaneous administration calculated as Vd/F = Dose/ apparent terminal elimination rate constant (Lambda[z])*AUC [0-infinity].
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Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Terminal Rate Constant (Kel)
Time Frame: Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Terminal rate constant of JNJ-64565111 is defined as the fraction of drug that is eliminated per unit of time (fraction/hour).
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Fourth Dose: Predose (Day 22), and at 72, 96, 144, 168, 312, 480, 720, and 1200 hours PD
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Number of Participants With Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity
Time Frame: First Dose: Predose (Day 1); Second Dose: predose (Day 8) Third Dose: predose (Day 15); Fourth Dose: predose (Day 22), 144, 480, 720, and 1200 hours post-dose.
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Immunogenicity will be measured by evaluating serum samples collected from participants.
Serum samples will be screened for antibodies binding to JNJ-64565111.
The titer of confirmed positive samples will be reported.
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First Dose: Predose (Day 1); Second Dose: predose (Day 8) Third Dose: predose (Day 15); Fourth Dose: predose (Day 22), 144, 480, 720, and 1200 hours post-dose.
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Change From Baseline in Body Weight
Time Frame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
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Body weight will be measured using a calibrated scale at each time a participant is weighed.
Calibration must be documented in a calibration log.
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Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
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Change From Baseline in Fasting Plasma Glucose (FPG)
Time Frame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
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Change from baseline in fasting plasma glucose (FPG) will be assessed.
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Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
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Change From Baseline in Hemoglobin A1c (HbA1c)
Time Frame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
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Change from baseline in HbA1c will be assessed.
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Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
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Change From Baseline in Fasting Lipids
Time Frame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
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Fasting plasma lipids were measured to determine the total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, very low-density lipoprotein cholesterol (VLDL-C), triglycerides and free fatty acids to understand the potential impact of study drug on cardiovascular disease risk.
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Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
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Change From Baseline for 24-hour Mean Plasma Glucose
Time Frame: Baseline, Day 26
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Mean plasma glucose defined as the total and/or incremental (that is, baseline-subtracted) area under the concentration (AUC) time curve over 0 to 24 hours, divided by 24.
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Baseline, Day 26
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Change From Baseline in C-peptide Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
Time Frame: Baseline, Day 26
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MMTT-Stimulated 6-Hour C-peptide AUC is the mean area under the C-peptide level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.
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Baseline, Day 26
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Change From Baseline in Total and/or Incremental Plasma Glucose Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
Time Frame: Baseline, Day 26
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MMTT-Stimulated 6-Hour total and/or incremental plasma glucose AUC is the mean area under the total and/or incremental plasma glucose level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.
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Baseline, Day 26
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Change From Baseline in Insulin Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
Time Frame: Baseline, Day 26
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MMTT-Stimulated 6-Hour Insulin AUC is the mean area under the insulin level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.
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Baseline, Day 26
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Change From Baseline in Glucagon Area Under the Curve (AUC) Calculated From a 6-Hour Mixed Meal Tolerance Test (MMTT)
Time Frame: Baseline, Day 26
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MMTT-Stimulated 6-Hour Glucagon AUC is the mean area under the glucagon level-time curve over the 6-hour period divided by the duration after a mixed-meal tolerance test.
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Baseline, Day 26
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Change From Baseline in 24-hour Blood Pressure
Time Frame: Baseline and Day 28
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Blood Pressure will be assessed by 24-hour ambulatory blood pressure and heart rate monitoring (ABPM) device by periodic measurements performed at 1 hour intervals for the first 14 hours, then at 2-hour intervals for the remaining 10 hours (that is, 19 measurements in total).
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Baseline and Day 28
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Change From Baseline in 24-hour Heart Rate
Time Frame: Baseline and Day 28
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Heart rate measurements will be assessed with a completely automated (ambulatory blood pressure and heart rate monitoring) device.
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Baseline and Day 28
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Change From Baseline in Body Mass Index (BMI)
Time Frame: Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
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Body Mass Index (BMI) is calculated by dividing the body weight (in kilogram) by the square of height (in meters).
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Baseline, Days 8, 15, 22, 28, 29, 35, 42, 52, and 72
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Change From Baseline Insulin Secretion as Assessed by the Insulinogenic Index
Time Frame: Baseline, Day 26
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Insulin secretion will be assessed by the insulinogenic index (Insulin 30-Insulin 0)/(Glucose 30-Glucose 0), by measuring the ratio of insulin to glucose.
The insulinogenic index is frequently used as a measure of beta cell function.
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Baseline, Day 26
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Change from Baseline in Insulin Secretion as Assessed by Homeostasis Model Assessment of Beta Cell Function (HOMA-%B)
Time Frame: Baseline, Day 26
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HOMA is used to quantify insulin resistance and beta-cell function from basal (fasting) glucose and insulin (or C-peptide) concentrations.
HOMA-B will be calculated by 20*I/(G-3.5)
where I is fasting plasma insulin (micro units/per milliliter [uU/mL]) and G is fasting plasma glucose (millimoles per liter [mmol/L]).
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Baseline, Day 26
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Change From Baseline in Insulin Sensitivity as Assessed by Matsuda Index
Time Frame: Baseline, Day 26
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The Matsuda index represents a composite of both hepatic and peripheral tissue sensitivity to insulin.
Insulin sensitivity by Matsuda Index will be calculated by (10,000/square root of [fasting glucose * fasting insulin] * [mean glucose * mean insulin during oral glucose tolerance test [OGTT]).
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Baseline, Day 26
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Change From Baseline in Insulin Sensitivity as Assessed by Homeostasis Model Assessment for Insulin Sensitivity (HOMA-%S)
Time Frame: Baseline, Day 26
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Insulin sensitivity will be assessed by Homeostasis Model Assessment (HOMA-%S) where HOMA-%S is 100/HOMA-Insulin Resistance [IR].
The HOMA-IR is the product of the blood Glucose and Insulin levels, divided by a constant.
HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (uU/mL) * fasting plasma glucose (mmol/L) / 22.5.
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Baseline, Day 26
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 1, 2017
Primary Completion (Actual)
February 19, 2018
Study Completion (Actual)
February 19, 2018
Study Registration Dates
First Submitted
July 28, 2017
First Submitted That Met QC Criteria
July 28, 2017
First Posted (Actual)
August 1, 2017
Study Record Updates
Last Update Posted (Actual)
April 18, 2023
Last Update Submitted That Met QC Criteria
April 13, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CR108339
- 64565111EDI1002 (Other Identifier: Janssen Research & Development, LLC)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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