Clinical trial NCT03618160: A Study to Assess the Safety, Tolerability and Pharmacokinetics of Subcutaneous (SC) Injections of JNJ-64565111 in Healthy Male Japanese Participants and to Assess Pharmacokinetics Following Subcutaneous Injections of JNJ-64565111 in Healthy Male Caucasian Participants
Official title: A Double-blind, Placebo-controlled, Randomized, Single Ascending Dose and Multiple Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics Following Subcutaneous Injections of JNJ-64565111 in Healthy Male Japanese Subjects and An Open-label, Single Dose Study to Assess Pharmacokinetics Following Subcutaneous Injections of JNJ-64565111 in Healthy Male Caucasian Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2018-08-07
Enrollment: 42
Sex: MALE
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: The purpose of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of JNJ-64565111 following single and multiple subcutaneous (SC) doses in healthy Japanese male participants.


Eligibility criteria: Inclusion Criteria:

* For Part 1 and Part 2, participant must be a Japanese male 20 to 65 years of age, inclusive, at the time of informed consent for screening. For Part 3, participant must be a Caucasian male (defined as white and all of his parents and grandparents are white as determined by participant's verbal report) 20 to 65 years of age, inclusive, at the time of informed consent for screening
* Participant must agree to use an adequate contraception method as deemed appropriate by the investigator; to always use a condom during sexual intercourse (even in case of prior vasectomy), or to remain abstinent, and not to donate sperm during the study and for 90 days after study drug administration. Participants should encourage their female partner to use an effective method of contraception (example, prescription oral contraceptives, contraceptive injections, intrauterine device, or contraceptive patch) in addition to the condom used by the male study participant
* Participant must have a body mass index (BMI) ranging from 25 to 40 kilogram per meter square (kg/m\^2), weighing 120 kilogram (kg) or less
* Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12 lead electrocardiogram (ECG) performed at screening
* Participant must be a non smoker for at least 1 month prior to screening. A positive urine smoking test (cotinine) at screening and/or admission (Day 2) will lead to exclusion

Exclusion Criteria:

* Participant having a history of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiovascular disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), significant pulmonary disease, including bronchospastic respiratory disease, hepatic or renal insufficiency, type 1 diabetes mellitus, type 2 diabetes mellitus (T2DM), diabetic ketoacidosis (DKA), pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study result
* Participant has taken any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen, from 14 days before the first dose of the study drug is scheduled until completion of the study
* Participant has received an experimental drug (including investigational vaccines) or used an experimental medical device within 3 months or within a period less than 5 times the drug's half life, whichever is longer, prior to screening
* Participant test positive for human immunodeficiency virus (HIV \[positive serology for HIV antigen/antibody\]), tests positive for hepatitis B virus surface antigen, or has antibodies to hepatitis C virus (HCV) at screening
* Participant has had major surgery (example, requiring general anesthesia) within 4 months before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study or within 6 months after study drug administration

Primary outcomes:
measure: Part 1 and Part 3: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to Day 35
measure: Part 1: Maximum Observed Serum Concentration (Cmax) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 1: Actual Sampling Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 1: Area Under Serum Concentration Curve From Time 0 to Time of the Last Measurable Concentration (AUC[0-Last]) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 1: Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC[0-Infinity]) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 1: Apparent Terminal Elimination Half-Life (t1/2) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 1: Apparent Volume of Distribution (V/F) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 1: Total Apparent Clearance (CL/F) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 2: Number of Participants With AEs as a Measure of Safety and Tolerability
timeFrame: Up to Day 72
measure: Part 2: Maximum Observed Serum Concentration (Cmax) of JNJ-64565111
timeFrame: Day 1: Predose, 8, 24, 48, 72, 120 hours postdose; Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose
measure: Part 2: Actual Sampling Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-64565111
timeFrame: Day 1: Predose, 8, 24, 48, 72, 120 hours postdose; Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose
measure: Part 2: Apparent Terminal Elimination Half-Life (t1/2) of JNJ-64565111
timeFrame: Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose
measure: Part 2: Apparent Volume of Distribution (V/F) of JNJ-64565111
timeFrame: Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose
measure: Part 2: Total Apparent Clearance (CL/F) of JNJ-64565111
timeFrame: Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose
measure: Part 2: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-64565111
timeFrame: Day 1: Predose, 8, 24, 48, 72, 120, 168 hours postdose; Day 22: 72, 96, 144, 168 hours postdose
measure: Part 2: Observed Serum Concentration Just Prior to the Beginning or the End of a Dosing Interval (Ctrough) of JNJ-64565111
timeFrame: Day 8: Predose ; Day 15: Predose; Day 22: Predose, 168 hours postdose
measure: Part 2: Average Concentration Over the Dosing Interval Tau (T) at Steady State (Caverage,ss) of JNJ-64565111
timeFrame: Day 22: Predose, 72, 96, 144, 168 hours postdose
measure: Part 2: Observed Accumulation Index (AR-AUC) of JNJ-64565111
timeFrame: Day 1: Predose, 8, 24, 48, 72, 120, 168 hours postdose; Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose
Secondary outcomes:
measure: Part 1 and 3: Number of Participants With Anti-Drug Antibodies (ADAs) to JNJ-64565111
timeFrame: Predose, 144 and 816 hours postdose
measure: Part 1 and Part 3: Change From Baseline in Body Weight
timeFrame: Baseline to Day 35
measure: Part 1 and Part 3: Change from Baseline in Fasting Plasma Glucose (FPG) Levels
timeFrame: Baseline to Day 35
measure: Part 1 and Part 3: Change From Baseline in Total Cholesterol
timeFrame: Baseline to Day 35
measure: Part 1 and Part 3: Change From Baseline in Low Density Lipoprotein- Cholesterol (LDL-C)
timeFrame: Baseline to Day 35
measure: Part 1 and Part 3: Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C)
timeFrame: Baseline to Day 35
measure: Part 1 and Part 3: Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C)
timeFrame: Baseline to Day 35
measure: Part 1 and Part 3: Change From Baseline in Triglycerides
timeFrame: Baseline to Day 35
measure: Part 1 and Part 3: Change From Baseline in Free Fatty Acids
timeFrame: Baseline to Day 35
measure: Part 2: Number of Participants With Anti-Drug Antibodies (ADAs) to JNJ-64565111
timeFrame: Predose on Day 1, 8, 15, 22 and then at 144, 480, 720, 1200 hours postdose
measure: Part 2: Change From Baseline in Body Weight
timeFrame: Baseline to Day 72
measure: Part 2: Change From Baseline in Fasting Plasma Glucose (FPG) Levels
timeFrame: Baseline to Day 72
measure: Part 2: Change From Baseline in Total Cholesterol
timeFrame: Baseline to Day 72
measure: Part 2: Change From Baseline in Low Density Lipoprotein- Cholesterol (LDL-C)
timeFrame: Baseline to Day 72
measure: Part 2: Change From Baseline in High-Density Lipoprotein-Choelsterol (HDL-C)
timeFrame: Baseline to Day 72
measure: Part 2: Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C)
timeFrame: Baseline to Day 72
measure: Part 2: Change From Baseline in Triglycerides
timeFrame: Baseline to Day 72
measure: Part 2: Change From Baseline in Free Fatty Acids
timeFrame: Baseline to Day 72
measure: Part 3: Maximum Observed Serum Concentration (Cmax) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 3: Actual Sampling Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 3: Area Under Serum Concentration Curve From Time 0 to Time of the Last Measurable Concentration (AUC[0-Last]) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 3: Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC[0-Infinity]) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 3: Apparent Terminal Elimination Rate Constant (Lambda [z]) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 3:Apparent Terminal Elimination Half-Life (t1/2) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 3: Apparent Volume of Distribution (V/F) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
measure: Part 3: Total Apparent Clearance (CL/F) of JNJ-64565111
timeFrame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Souseikai Hakata Clinic
city: Tokyo
country: Japan
facility: Sumida Hospital
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K Clinical Trial
role: STUDY_DIRECTOR
References: