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A Study to Assess the Relative Oral Bioavailability of a Single Dose of JNJ-63623872/Oseltamivir Fixed-dose Combination Tablet and Single Agent Concept Formulations of JNJ-63623872 Compared to Their Respective Reference Formulation in Healthy Adult Participants

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT03023852
Lead Sponsor
Janssen-Cilag International NV
Brief Summary

The purpose of this study is to assess the rate and extent of absorption of JNJ63623872 following administration of a single oral dose of 2\*300 milligram (mg) given as 2 concept single agent tablet formulations compared to the administration of 2\*300 mg JNJ63623872 reference tablets, under fasted conditions in healthy adult participants and to assess the rate and extent of absorption of JNJ63623872 and oseltamivir following administration of a single oral dose of 2\*300 mg/37.5 mg JNJ63623872/ oseltamivir given as a concept fixed dose combination (FDC) tablet formulation compared to the coadministration of 2\*300 mg JNJ63623872 tablets (reference formulation) and 1\*75 mg oseltamivir capsule, under fasted conditions in healthy adult participants.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
45
Inclusion Criteria
  • A female participant must have a negative serum beta-human chorionic gonadotropin pregnancy test at screening and on Day -1 in each treatment period
  • Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies
  • A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 90 days after receiving the last dose of study drug
  • Participant must have a body mass index (BMI), weight kilogram per height square meter square [kg]/height^2 [m]^2) between 18.0 and 30.0 kilogram per meter square (kg/m^2) (extremes included) at screening. The minimum weight will be 50.0 kilogram (kg)
  • Participant must have a blood pressure (supine after at least 5 minutes rest) between 90 and 140 millimeters of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic at screening
  • Participant must be non-smoker for at least 3 months prior to screening
Exclusion Criteria
  • Participant has history or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders, lipid abnormalities, significant pulmonary disease, diabetes mellitus, hepatic or renal insufficiency, gastrointestinal disease, 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
  • Participant with a past history of heart arrhythmias (extrasystoli, tachycardia at rest), or history of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome)
  • Participant with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
  • Participant has known allergy to heparin or history of heparin induced thrombocytopenia
  • Participant has donated blood or blood products or had substantial loss of blood (more than 500 milliliter (mL) within 3 months before the first administration of study drug or intention to donate blood or blood products during the study
  • A woman who is pregnant, or breast-feeding, or planning to become pregnant during this study, or a woman of childbearing potential who is unwilling to use acceptable methods of contraception
  • Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening
  • Participant has a history of human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection, or tests positive for HIV-1 or -2 at screening

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Panel 1: Group 1JNJ-63623872Participants will receive Treatment A (JNJ-63623872 600 milligram (mg) (2\*300 mg) oral tablets \[reference\]) followed by Treatment B (JNJ- 63623872 600 mg (2\*300 mg) concept oral tablet formulation 1 (test 1) and then Treatment C (JNJ-63623872 600 mg (2\*300 mg) concept oral tablet formulation 2 (test 2). Each treatment period will be separated 7 days washout period.
Panel 1: Group 4JNJ-63623872Participants in Group 4 will receive Treatment B followed by Treatment C and then Treatment A with a washout period of minimum 7 days.
Panel 2: Group 7OseltamivirParticipants in Group 7 will receive Treatment D \[JNJ-63623872/37.5 mg Oseltamivir oral fixed dose combination (FDC) tablet concept formulation (test 3)\] followed by Treatment E (JNJ-63623872 600 mg, administered as 2\*300 mg and Oseltamivir 75 mg, administered as 1\*75 mg). Both treatment periods will be separated with a minimum of 7 days washout period.
Panel 2: Group 7JNJ-63623872Participants in Group 7 will receive Treatment D \[JNJ-63623872/37.5 mg Oseltamivir oral fixed dose combination (FDC) tablet concept formulation (test 3)\] followed by Treatment E (JNJ-63623872 600 mg, administered as 2\*300 mg and Oseltamivir 75 mg, administered as 1\*75 mg). Both treatment periods will be separated with a minimum of 7 days washout period.
Panel 1: Group 3JNJ-63623872Participants in Group 3 will receive Treatment B followed by Treatment A and then Treatment C with a washout period of minimum 7 days.
Panel 1: Group 6JNJ-63623872Participants in Group 6 will receive Treatment C followed by Treatment B and then Treatment A with a washout period of minimum 7 days.
Panel 2: Group 8OseltamivirParticipants in Group 8 will receive Treatment E followed by Treatment D with a washout period of minimum 7 days.
Panel 2: Group 8JNJ-63623872Participants in Group 8 will receive Treatment E followed by Treatment D with a washout period of minimum 7 days.
Panel 1: Group 2JNJ-63623872Participants in Group 2 will receive Treatment A followed by Treatment C and then Treatment B with a washout period of minimum 7 days.
Panel 1: Group 5JNJ-63623872Participants in Group 5 will receive Treatment C followed by Treatment A and then Treatment B with a washout period of minimum 7 days.
Primary Outcome Measures
NameTimeMethod
Apparent Terminal Elimination Rate Constant (Lambda [z])Predose, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, 72 h and 96 hours postdose on Day 5

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

Maximum Observed Plasma Concentration (Cmax)Predose, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, 72 h and 96 hours postdose on Day 5

The Plasma Concentration (Cmax) is defined as maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax)Predose, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, 72 h and 96 hours postdose on Day 5

The Tmax is defined as actual sampling time to reach maximum observed plasma concentration.

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])Predose, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, 72 h and 96 hours postdose on Day 5

The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration Time (AUC [0-Last])Predose, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, 72 h and 96 hours postdose on Day 5

AUC last is area under the plasma concentration-time curve from time zero to last quantifiable concentration time.

Apparent Terminal Elimination Half-life (t1/2)Predose, 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 12 h, 16 h, 24 h, 48 h, 72 h and 96 hours postdose on Day 5

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Adverse Events (AEs)Up to follow-up (within 10 to 14 days after last dose)

Safety and Tolerability

Taste Questionnaire AssessmentDay 1

A taste questionnaire will be completed by the participants of Panel 2, group 7 within 5 to 15 minutes after intake of the FDC tablet (Treatment E) to evaluate the taste of the oral FDC tablet formulation under fasted conditions. The Taste questionnaire consists of 4 parts (sweetness, bitterness, flavour and overall); each parts is scored on 4 points , i.e. none, weak, moderate and strong.

Swallowability AssessmentDay 1

Swallowability will be assessed in participants of Panel 2 group 7 on a scale of 1-7; how difficult/easy was it to swallow this tablet. In the scale 0=very difficult and 7=very easy.

Trial Locations

Locations (1)

SGS Life Science Services

🇧🇪

Antwerp, Belgium

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