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

• ClinicalTrials.gov Identifier: NCT02862431
• Recruitment Status: Terminated
• First Posted: August 11, 2016
• Last Update Posted: March 29, 2018
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

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.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Drug: JNJ-64565111; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 2016
• Actual Primary Completion Date: November 2016
• Actual Study Completion Date: December 2016

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to Day 72 ]

Secondary Outcome Measures :

1. Number of Participants With Incidence of Anti-JNJ-64565111 Antibodies as Measure of Immunogenicity [ Time Frame: Up to Day 72 ]
2. Change From Baseline in Body Weight [ Time Frame: Baseline, up to Day 72 ]
3. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to Day 72 ]
   Maximum observed plasma concentration (Cmax) will be assessed after first dose and last dose.
4. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Up to Day 72 ]
   Tmax defined as actual sampling time to reach maximum observed analyte concentration will be assessed after first dose and last dose.
5. Area Under Concentration from time zero to the last quantifiable concentration AUC(0-last) [ Time Frame: Up to Day 72 ]
   AUC from time zero to the last quantifiable concentration will be assessed after first dose and after last dose.
6. Area Under Curve over the dosing interval AUC(0-tau) [ Time Frame: Up to Day 72 ]
   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.
7. Elimination Half-Life (t1/2) [ Time Frame: Up to Day 72 ]
   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.
8. Apparent Clearance (CL/F) [ Time Frame: Up to Day 72 ]
   The Oral Clearance (CL/F) is the clearance based on oral bioavailability. CL/F will be assessed after first dose and last dose.
9. Apparent Volume of Distribution (V/F) [ Time Frame: Up to Day 72 ]
   Apparent volume of distribution will be assessed after first dose and last dose.
10. Terminal Rate Constant (K) [ Time Frame: Up to Day 72 ]
    Terminal rate constant will be assessed after first dose and last dose.
11. Average concentration over the dosing interval at steady state (Caverage,ss) [ Time Frame: Up to Day 72 ]
    The average concentration over the dosing interval at steady state, calculated as AUC(0-tau)/tau and will be assessed after last dose.
12. Minimum Observed Plasma Concentration (Cmin) [ Time Frame: Up to Day 72 ]
    The Cmin is the minimum observed plasma concentration over the dosing interval at steady state. Cmin will be assessed after last dose.
13. Area Under Curve from time zero extrapolated to infinity AUC(0-inf) [ Time Frame: Up to Day 72 ]
    AUC from time zero extrapolated to infinity will be assessed after last dose.
14. Accumulation Ratio [ Time Frame: Up to Day 72 ]
    Accumulation ratio calculated as AUC(0-tau), Day 22 / AUC(0-tau), Day 1 will be assessed after last dose.
15. Change From Baseline in Blood Pressure [ Time Frame: Baseline, up to Day 72 ]
16. Change From Baseline in Heart Rate [ Time Frame: Baseline, up to Day 72 ]
17. Change From Baseline for 24-hour Mean Plasma Glucose [ Time Frame: Baseline, Day 26 ]
    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.
18. Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline, up to Day 72 ]
19. Change From Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, up to Day 72 ]
20. Change From Baseline on Fasting Lipids [ Time Frame: Baseline, up to Day 72 ]
    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.
21. Change From Baseline in Insulin Secretion [ Time Frame: Baseline, Day 26 ]
22. Change From Baseline in Insulin Sensitivity [ Time Frame: Baseline, Day 26 ]
23. Change From Baseline for C-peptide [ Time Frame: Baseline, Day 26 ]
24. Change From Baseline for Glucagon [ Time Frame: Baseline, Day 26 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

Germany

Neuss, Germany

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

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

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02862431
• Other Study ID Numbers: CR108166; 64565111EDI1001 ( Other Identifier: Janssen Research & Development, LLC ); 2016-001084-37 ( EudraCT Number )
• First Posted: August 11, 2016
• Last Update Posted: March 29, 2018
• Last Verified: March 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases