Safety, Tolerability, Pharmacokinetic and Absolute Bioavailability Study of JNJ-63623872 Administered as an Intravenous Infusion and a 600-Milligram (mg) Oral Dose in Healthy Adults

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: JNJ-63623872

Study type: Interventional

Funder types: Industry

Identifiers

NCT02860806

2016-000921-37 (EudraCT Number)

63623872FLZ1002 (Other Identifier)

CR108196

Details and patient eligibility

About

The purpose of this study is to characterize the single-dose pharmacokinetic (PK) of single escalating intravenous (IV) doses of JNJ-63623872 administered as a continuous infusion; to evaluate the safety and tolerability of single escalating IV doses of JNJ-63623872 administered as a continuous infusion; to characterize the single-dose PK of JNJ-63623872 of one selected dose administered as a continuous IV infusion at various durations and to characterize the single- and repeat-dose PK of JNJ-63623872 administered as a continuous infusion.

Enrollment: 66 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• A female participant (except if postmenopausal) must have a negative serum beta- human chorionic gonadotropin (beta-hCG) pregnancy test at screening and on Day -1 of each treatment period
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 90 days after discontinuation of study drug
• During the study and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study drug, in addition to the highly effective method of contraception in the female partner, a man regardless of having been vasectomized: 1) who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (example, condom with spermicidal foam/gel/film/cream/suppository), 2) must agree not to donate sperm and 3) who is sexually active with a pregnant women must use a condom
• Must have a Body Mass Index (BMI); weight kilogram [kg]/height^2 [m]^2) between 18.0 and 30.0 kilogram per meter square (kg/m^2) (extremes included) at Screening
• Must have a blood pressure (supine after at least 5 minutes rest and standing after at least 1 minute standing) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic at Screening

Exclusion criteria

• Has a history of current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, 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 results
• With a past history of heart arrhythmias (extrasystoli, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (example, hypokalemia, family history of long QT Syndrome)
• Has known allergies, hypersensitivity, or intolerance to JNJ-63623872 or its excipients
• With any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
• With a history of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy diagnosed in previous studies with experimental drugs
• Has a 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
• Has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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66 participants in 10 patient groups

Part 1: Period 1 (JNJ-63623872 100 mg or Placebo)

Experimental group

Description:

Participants will receive a single intravenous (IV) infusion of JNJ-63623872 100 milligram (mg) \[3 milligram per milliliters (mg/mL) solution\] (Treatment A) or matching placebo (Treatment D) over 120 minutes.

Treatment:

Drug: Placebo

Drug: JNJ-63623872

Part 1: Period 2 (JNJ-63623872 200 mg or Placebo)

Experimental group

Description:

Participants will receive a single IV infusion of JNJ-63623872 200 mg (3 mg/mL solution) (Treatment B) or matching placebo (Treatment D) over 120 minutes.

Treatment:

Drug: Placebo

Drug: JNJ-63623872

Part 1: Period 3 (JNJ-63623872 300 mg or Placebo)

Experimental group

Description:

Participants will receive a single IV infusion of JNJ-63623872 300 mg (3 mg/mL solution) (Treatment C) or matching placebo (Treatment D) over 120 minutes.

Treatment:

Drug: Placebo

Drug: JNJ-63623872

Part 2: Group 1 (EFG)

Experimental group

Description:

Participants will receive a single IV 300-mg infusion of JNJ-63623872 (3 mg/mL solution) over x minutes (Treatment E) followed by a single IV 300-mg infusion of JNJ-63623872 (3 mg/mL solution) over y minutes (Treatment F), then a single oral 600-mg dose (2\* 300 mg tablets) of JNJ-63623872 under fasted conditions (Treatment G). Study drug administration in subsequent treatment periods will be separated by a washout period of at least 7 days.

Treatment:

Drug: JNJ-63623872

Part 2: Group 2 (FGE)

Experimental group

Description:

Participants will receive Treatment F, then Treatment G followed by Treatment E. Study drug administration in subsequent treatment periods will be separated by a washout period of at least 7 days.

Treatment:

Drug: JNJ-63623872

Part 2: Group 3 (GEF)

Experimental group

Description:

Participants will receive Treatment G, then Treatment E followed by Treatment F. Study drug administration in subsequent treatment periods will be separated by a washout period of at least 7 days.

Treatment:

Drug: JNJ-63623872

Part 2: Group 4 (GFE)

Experimental group

Description:

Participants will receive Treatment G, then Treatment F, followed by Treatment E. Study drug administration in subsequent treatment periods will be separated by a washout period of at least 7 days.

Treatment:

Drug: JNJ-63623872

Part 2: Group 5 (FEG)

Experimental group

Description:

Participants will receive Treatment F, then Treatment E followed by Treatment G. Study drug administration in subsequent treatment periods will be separated by a washout period of at least 7 days.

Treatment:

Drug: JNJ-63623872

Part 2: Group 6 (EGF)

Experimental group

Description:

Participants will receive Treatment E, then Treatment G followed by Treatment F. Study drug administration in subsequent treatment periods will be separated by a washout period of at least 7 days.

Treatment:

Drug: JNJ-63623872

Part 3: JNJ-63623872 300 mg

Experimental group

Description:

Participants will receive multiple IV infusions of JNJ-63623872 300 mg (3 mg/mL) solution every 12 hours on Days 1 to 10, with only a morning dose on Day 10. Duration of infusion and dose will be selected after Part 2 of this study is completed.

Treatment:

Drug: JNJ-63623872