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

Phase 1TerminatedNCT03618160

Janssen Pharmaceutical K.K.42 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

JNJ-64565111DRUG

Participants in Cohorts 1 to 3 will receive a single SC low, medium, and high dose of JNJ-64565111 respectively on Day 1, participants in Cohorts 4 to 6 will receive weekly multiple SC low, high and medium dose of JNJ-64565111 respectively on Days 1, 8, 15, and 22, under fasted conditions. Participants in Cohort 7 will receive a single SC medium dose of JNJ-64565111 on Day 1, under fasted conditions.

PlaceboDRUG

Participants will receive SC injection of matching placebo on Day 1 in all cohorts of Part 1 and on Days 1, 8, 15, and 22 in Part 2 under fasted conditions.

Eligibility

Sex: MALEMin age: 20 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (2)

Souseikai Hakata Clinic

Fukuoka, Japan

Sumida Hospital

Tokyo, Japan

Outcomes

Primary Outcomes

Part 1 and Part 3: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability

An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.

Time frame: Up to Day 35

Part 1: Maximum Observed Serum Concentration (Cmax) of JNJ-64565111

Cmax is defined as the maximum observed serum concentration.

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 1: Actual Sampling Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-64565111

Tmax is defined as the actual sampling time to reach maximum observed serum concentration of JNJ-64565111.

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 1: Area Under Serum Concentration Curve From Time 0 to Time of the Last Measurable Concentration (AUC[0-Last]) of JNJ-64565111

AUC(0-Last) is defined as the AUC from time 0 to the time of the last measurable (non-below quantification limit \[non-BQL\]) serum concentration.

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 1: Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC[0-Infinity]) of JNJ-64565111

AUC (0-infinity) is defined as the area under the serum concentration-time curve from time zero to infinite time calculated as the sum of AUC(0-last) and Clast/ lambda (z); wherein AUC(0-last) is area under the serum concentration time curve from time zero to last measurable serum concentration, Clast is the last observed measurable (non-BQL) serum concentration, and lambda (z) is the apparent terminal elimination rate constant.

Data from ClinicalTrials.gov

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Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 1: Apparent Terminal Elimination Half-Life (t1/2) of JNJ-64565111

t1/2 is defined as the apparent terminal elimination half life, and is calculated as 0.693/lambda (z).

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 1: Apparent Volume of Distribution (V/F) of JNJ-64565111

V/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after subcutaneous dose (V/F) is influenced by the fraction absorbed and calculated as dose/(lambda (z)\*AUC\[0-infinity\]).

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 1: Total Apparent Clearance (CL/F) of JNJ-64565111

CL/F is defined as the total apparent clearance of drug after extravascular administration calculated as: dose divided by AUC\[0-infinity\].

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 2: Number of Participants With AEs as a Measure of Safety and Tolerability

Time frame: Up to Day 72

Part 2: Maximum Observed Serum Concentration (Cmax) of JNJ-64565111

Cmax is defined as the maximum observed serum concentration.

Time frame: Day 1: Predose, 8, 24, 48, 72, 120 hours postdose; Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose

Part 2: Actual Sampling Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-64565111

Tmax is defined as the actual sampling time to reach maximum observed serum concentration of JNJ-64565111.

Time frame: Day 1: Predose, 8, 24, 48, 72, 120 hours postdose; Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose

Part 2: Apparent Terminal Elimination Half-Life (t1/2) of JNJ-64565111

t1/2 is defined as the apparent terminal elimination half life, and is calculated as 0.693/lambda (z).

Time frame: Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose

Part 2: Apparent Volume of Distribution (V/F) of JNJ-64565111

Time frame: Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose

Part 2: Total Apparent Clearance (CL/F) of JNJ-64565111

CL/F is the total apparent clearance of drug after extravascular administration calculated as: dose divided by AUCtau.

Time frame: Day 22: Predose, 72, 96, 144, 168, 312, 480, 720, 1200 hours postdose

Part 2: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-64565111

AUCtau is defined as the measure of the serum drug concentration from time zero to end of dosing interval.

Time frame: Day 1: Predose, 8, 24, 48, 72, 120, 168 hours postdose; Day 22: 72, 96, 144, 168 hours postdose

Part 2: Observed Serum Concentration Just Prior to the Beginning or the End of a Dosing Interval (Ctrough) of JNJ-64565111

Ctrough is defined as the observed serum concentration just prior to the beginning or the end of a dosing interval.

Time frame: Day 8: Predose ; Day 15: Predose; Day 22: Predose, 168 hours postdose

Part 2: Average Concentration Over the Dosing Interval Tau (T) at Steady State (Caverage,ss) of JNJ-64565111

Caverage,ss is defined as area under the serum concentration time curve observed during a dosing interval (tau) at steady state) will be calculated as AUCtau/Tau.

Time frame: Day 22: Predose, 72, 96, 144, 168 hours postdose

Part 2: Observed Accumulation Index (AR-AUC) of JNJ-64565111

AR-AUC is determined after multiple dose administration of JNJ-64565111 and calculated by using the equation: AUCtau, Day 22 divided by AUCtau, Day 1.

Time frame: 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

Part 1 and 3: Number of Participants With Anti-Drug Antibodies (ADAs) to JNJ-64565111

Number of participants with anti-drug antibodies (ADAs) to JNJ-64565111 will be reported.

Time frame: Predose, 144 and 816 hours postdose

Part 1 and Part 3: Change From Baseline in Body Weight

Change from baseline in body weight will be reported.

Time frame: Baseline to Day 35

Part 1 and Part 3: Change from Baseline in Fasting Plasma Glucose (FPG) Levels

Change from baseline in FPG levels will be reported.

Time frame: Baseline to Day 35

Part 1 and Part 3: Change From Baseline in Total Cholesterol

Change from baseline in total cholesterol will be reported.

Time frame: Baseline to Day 35

Part 1 and Part 3: Change From Baseline in Low Density Lipoprotein- Cholesterol (LDL-C)

Change from baseline in LDL-C will be reported.

Time frame: Baseline to Day 35

Part 1 and Part 3: Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C)

Change from baseline in HDL-C will be reported.

Time frame: Baseline to Day 35

Part 1 and Part 3: Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C)

Change from baseline in VLDL-C will be reported.

Time frame: Baseline to Day 35

Part 1 and Part 3: Change From Baseline in Triglycerides

Change from baseline in Triglycerides will be reported.

Time frame: Baseline to Day 35

Part 1 and Part 3: Change From Baseline in Free Fatty Acids

Change from baseline in free fatty acids will be reported.

Time frame: Baseline to Day 35

Part 2: Number of Participants With Anti-Drug Antibodies (ADAs) to JNJ-64565111

Number of participants with ADAs to JNJ-64565111 will be reported.

Time frame: Predose on Day 1, 8, 15, 22 and then at 144, 480, 720, 1200 hours postdose

Part 2: Change From Baseline in Body Weight

Change from baseline in body weight will be reported.

Time frame: Baseline to Day 72

Part 2: Change From Baseline in Fasting Plasma Glucose (FPG) Levels

Change from baseline in FPG levels will be reported.

Time frame: Baseline to Day 72

Part 2: Change From Baseline in Total Cholesterol

Change from baseline in total cholesterol will be reported.

Time frame: Baseline to Day 72

Part 2: Change From Baseline in Low Density Lipoprotein- Cholesterol (LDL-C)

Change from baseline in LDL-C will be reported.

Time frame: Baseline to Day 72

Part 2: Change From Baseline in High-Density Lipoprotein-Choelsterol (HDL-C)

Change from baseline in HDL-C will be reported.

Time frame: Baseline to Day 72

Part 2: Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C)

Change from baseline in VLDL-C will be reported.

Time frame: Baseline to Day 72

Part 2: Change From Baseline in Triglycerides

Change from baseline in triglycerides will be reported.

Time frame: Baseline to Day 72

Part 2: Change From Baseline in Free Fatty Acids

Change from baseline in free fatty acids will be reported.

Time frame: Baseline to Day 72

Part 3: Maximum Observed Serum Concentration (Cmax) of JNJ-64565111

Cmax is defined as the maximum observed serum concentration.

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 3: Actual Sampling Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-64565111

Tmax is defined as the actual sampling time to reach maximum observed serum concentration of JNJ-64565111.

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 3: Area Under Serum Concentration Curve From Time 0 to Time of the Last Measurable Concentration (AUC[0-Last]) of JNJ-64565111

AUC(0-Last) is defined as the AUC from time 0 to the time of the last measurable non-below quantification limit serum concentration.

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 3: Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC[0-Infinity]) of JNJ-64565111

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 3: Apparent Terminal Elimination Rate Constant (Lambda [z]) of JNJ-64565111

Lambda (z) is the apparent terminal elimination rate-constant, estimated by linear regression using the terminal log linear phase of the log transformed concentration vs time curve.

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 3:Apparent Terminal Elimination Half-Life (t1/2) of JNJ-64565111

t1/2 is defined the apparent terminal elimination half life, and is calculated as 0.693/lambda (z).

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 3: Apparent Volume of Distribution (V/F) of JNJ-64565111

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose

Part 3: Total Apparent Clearance (CL/F) of JNJ-64565111

CL/F is defined as the total apparent clearance of drug after extravascular administration calculated as: dose divided by AUC\[0-infinity\].

Time frame: Predose, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 144, 216, 384, 672, and 816 hours postdose