A Crossover Study to Assess the Drug-drug Interaction of Acid Reducing Agent(s) on the Pharmacokinetics of a Single Oral Dose of Lumicitabine (JNJ-64041575) in Healthy Adult Participants
- Registration Number
- NCT03468777
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The main purpose of study is to evaluate the effect of multiple-dose administration of lansoprazole (and optional: time-separated single dose administration of ranitidine) on the pharmacokinetics (PK) of JNJ-63549109 after a single dose of lumicitabine in healthy adult participants, under fasted (and optional: fed) conditions.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 18
Inclusion Criteria
- Participant must be healthy on the basis of medical history, physical examination, 12 lead electrocardiogram (ECG), vital signs, and laboratory tests performed at screening
- Participant must have a body mass index (BMI); weight in kg divided by the square of height in meters) between 18.0 and 30.0 kilogram per square meter (kg/m^2), extremes included, and a body weight not less than 50.0 kg, inclusive, at screening
- Participant must have a blood pressure between 90 and 140 millimeter of mercury (mmHg) systolic, extremes included, and no higher than 90 mmHg diastolic. If blood pressure is out of range, 1 repeated assessment is permitted after an additional 5 minutes of rest
- Participants must have normal values for alanine transaminase (ALT) and aspartate aminotransferase (AST) (less than or equal to (<=) 1.0*upper limit of laboratory normal range [ULN])
- Participant must have a normal renal function (estimated glomerular filtration rate [eGFR] greater than or equal to (>=) 90 milliliter per minute per 1.73 meter per square (mL/min/1.73m^2) determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)
Exclusion Criteria
- Participant has a history of current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease (example, glucose 6 phosphate dehydrogenase deficiency), 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, seizure disorders, or any other illness, that in the investigator's and/or sponsor's medical monitor opinion should exclude the participant or that could interfere with the interpretation of the study results
- Participant has a history of human immunodeficiency virus type 1 (HIV-1) or type 2 (HIV-2) antibody positive, or tests positive for HIV-1 or -2 at screening
- Participant with a history of clinically significant drug allergy such as, but not limited to, sulfonamides, or drug allergy diagnosed in previous studies with experimental drugs
- Participant has known allergies, hypersensitivity, or intolerance to lumicitabine, proton pump inhibitors (PPIs), H2 blockers or their excipients
- Participants with evidence of any active infection, or participants with presence of any febrile illness or symptoms of upper or lower respiratory tract infection in the 14 days before the (first) administration of study drugs
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Optional Part 3: Treatment Sequence (EFD) Ranitidine Participants will receive Treatment E on Days 1 to 5 of period 1 then Treatment F on Day 1 of period 2 followed by Treatment D on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (FDE) Lumicitabine Participants will receive Treatment F on Days 1 of period 1 then Treatment D on Day 1 of period 2 followed by Treatment E on Days 1 to 5 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Part 1: Treatment Sequence (ABC) Lansoprazole Participants will receive Treatment A as a single oral dose of 1000 milligram (mg) lumicitabine (4\*250 mg tablets) under fasted condition on Day 1 of period 1 then Treatment B as a single oral dose of 30 mg lansoprazole under fasted condition on Days 1 to 4 and on Day 5 (administered 2 hours before a single oral dose of 1,000 mg lumicitabine) in period 2 followed by Treatment C (optional Part 2) as a single dose of 150 mg ranitidine administered after 2 hours of single dose of 1000 mg lumicitabine (4\*250 mg tablets) under fasted condition on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Part 1: Treatment Sequence (ABC) Ranitidine Participants will receive Treatment A as a single oral dose of 1000 milligram (mg) lumicitabine (4\*250 mg tablets) under fasted condition on Day 1 of period 1 then Treatment B as a single oral dose of 30 mg lansoprazole under fasted condition on Days 1 to 4 and on Day 5 (administered 2 hours before a single oral dose of 1,000 mg lumicitabine) in period 2 followed by Treatment C (optional Part 2) as a single dose of 150 mg ranitidine administered after 2 hours of single dose of 1000 mg lumicitabine (4\*250 mg tablets) under fasted condition on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Part 1: Treatment Sequence (BAC) Lumicitabine Participants will receive Treatment B on Days 1 to 5 of period 1 then Treatment A on Day 1 of period 2 followed by Treatment C (optional Part 2) on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Part 1: Treatment Sequence (BAC) Lansoprazole Participants will receive Treatment B on Days 1 to 5 of period 1 then Treatment A on Day 1 of period 2 followed by Treatment C (optional Part 2) on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (DEF) Lansoprazole Participants will receive Treatment D as a single oral dose of 1000 mg lumicitabine (4\*250 mg tablets) after standardized breakfast on Day 1 of period 1 then Treatment E as a single oral dose of 30 mg lansoprazole under fasted condition on Days 1 to 4 and on Day 5 (administered 2 hours before a single oral dose of 1,000 mg lumicitabine) in period 2 followed by Treatment F as a single oral dose of 150 mg ranitidine administered after 2 hours after a single oral dose of 1000 mg lumicitabine (4\*250 mg tablets) after standardized breakfast on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Part 1: Treatment Sequence (BAC) Ranitidine Participants will receive Treatment B on Days 1 to 5 of period 1 then Treatment A on Day 1 of period 2 followed by Treatment C (optional Part 2) on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (DEF) Ranitidine Participants will receive Treatment D as a single oral dose of 1000 mg lumicitabine (4\*250 mg tablets) after standardized breakfast on Day 1 of period 1 then Treatment E as a single oral dose of 30 mg lansoprazole under fasted condition on Days 1 to 4 and on Day 5 (administered 2 hours before a single oral dose of 1,000 mg lumicitabine) in period 2 followed by Treatment F as a single oral dose of 150 mg ranitidine administered after 2 hours after a single oral dose of 1000 mg lumicitabine (4\*250 mg tablets) after standardized breakfast on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (EFD) Lansoprazole Participants will receive Treatment E on Days 1 to 5 of period 1 then Treatment F on Day 1 of period 2 followed by Treatment D on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (FED) Ranitidine Participants will receive Treatment F on Day 1 of period 1 then Treatment E on Days 1 to 5 of period 2 followed by Treatment D on Days 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (FDE) Lansoprazole Participants will receive Treatment F on Days 1 of period 1 then Treatment D on Day 1 of period 2 followed by Treatment E on Days 1 to 5 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (FDE) Ranitidine Participants will receive Treatment F on Days 1 of period 1 then Treatment D on Day 1 of period 2 followed by Treatment E on Days 1 to 5 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (FED) Lumicitabine Participants will receive Treatment F on Day 1 of period 1 then Treatment E on Days 1 to 5 of period 2 followed by Treatment D on Days 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (EDF) Lansoprazole Participants will receive Treatment E on Days 1 to 5 of period 1 then Treatment D on Day 1 of period 2 followed by Treatment F on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (EDF) Ranitidine Participants will receive Treatment E on Days 1 to 5 of period 1 then Treatment D on Day 1 of period 2 followed by Treatment F on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (DFE) Lansoprazole Participants will receive Treatment D on Day 1 period 1 then Treatment F on Day 1 of period 2 followed by Treatment E on Days 1 to 5 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (DFE) Ranitidine Participants will receive Treatment D on Day 1 period 1 then Treatment F on Day 1 of period 2 followed by Treatment E on Days 1 to 5 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Part 1: Treatment Sequence (ABC) Lumicitabine Participants will receive Treatment A as a single oral dose of 1000 milligram (mg) lumicitabine (4\*250 mg tablets) under fasted condition on Day 1 of period 1 then Treatment B as a single oral dose of 30 mg lansoprazole under fasted condition on Days 1 to 4 and on Day 5 (administered 2 hours before a single oral dose of 1,000 mg lumicitabine) in period 2 followed by Treatment C (optional Part 2) as a single dose of 150 mg ranitidine administered after 2 hours of single dose of 1000 mg lumicitabine (4\*250 mg tablets) under fasted condition on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (DEF) Lumicitabine Participants will receive Treatment D as a single oral dose of 1000 mg lumicitabine (4\*250 mg tablets) after standardized breakfast on Day 1 of period 1 then Treatment E as a single oral dose of 30 mg lansoprazole under fasted condition on Days 1 to 4 and on Day 5 (administered 2 hours before a single oral dose of 1,000 mg lumicitabine) in period 2 followed by Treatment F as a single oral dose of 150 mg ranitidine administered after 2 hours after a single oral dose of 1000 mg lumicitabine (4\*250 mg tablets) after standardized breakfast on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (EFD) Lumicitabine Participants will receive Treatment E on Days 1 to 5 of period 1 then Treatment F on Day 1 of period 2 followed by Treatment D on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (EDF) Lumicitabine Participants will receive Treatment E on Days 1 to 5 of period 1 then Treatment D on Day 1 of period 2 followed by Treatment F on Day 1 of period 3. A washout period of at least 21 days will be maintained between each treatment period. Optional Part 3: Treatment Sequence (DFE) Lumicitabine Participants will receive Treatment D on Day 1 period 1 then Treatment F on Day 1 of period 2 followed by Treatment E on Days 1 to 5 of period 3. A washout period of at least 21 days will be maintained between each treatment period.
- Primary Outcome Measures
Name Time Method Observed Plasma Concentration at 12 Hours Post dose (C12h) of JNJ-63549109 (Metabolite of JNJ- 64041575) 12 hours postdose (Day 1) C12h is observed plasma concentration at 12 hours post dose.
Observed Plasma Concentration at 24 Hours Post dose (C24h) of JNJ-63549109 (Metabolite of JNJ- 64041575) 24 hours postdose (Day 2) C24h is observed plasma concentration at 24 hours post dose.
Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of JNJ- 64041575) Predose, 15 minutes (min), 30 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) Cmax is the maximum observed plasma concentration.
Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-63549109 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) 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 (0-last) and C (0-last)/ lambda(z); wherein AUC (0- last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-63549109 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) Tmax is the actual sampling time to reach maximum observed plasma concentration.
Area Under Plasma Concentration Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of JNJ-63549109 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) Area under the plasma concentration time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
Elimination Half-Life (T1/2) of JNJ-63549109 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) T1/2 is the apparent terminal elimination half-life, calculated as 0.693/Lambda(z).
Elimination Rate Constant (Lambda[z]) of JNJ-63549109 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) Lambda\[z\] is the apparent terminal elimination rate constant, estimated by linear regression using the terminal logarithmic (log)-linear phase of the log-transformed concentration vs time data.
- Secondary Outcome Measures
Name Time Method Observed Plasma Concentration at 12 Hours Post dose (C12h) of JNJ-64167896 (Metabolite of JNJ- 64041575) 12 hours postdose (Day 1) C12h is observed plasma concentration at 12 hours post dose.
Observed Plasma Concentration at 24 Hours Post dose (C24h) of JNJ-64167896 (Metabolite of JNJ- 64041575) 24 hours postdose (Day 2) C24h is observed plasma concentration at 24 hours post dose.
Maximum Observed Plasma Concentration (Cmax) of JNJ-64167896 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) Cmax is the maximum observed plasma concentration.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-64167896 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) Tmax is the actual sampling time to reach maximum observed plasma concentration.
Area Under Plasma Concentration Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of JNJ-64167896 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) Area under the plasma concentration time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64167896 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) 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 (0-last) and C (0-last)/ lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
Elimination Half-Life (T1/2) of JNJ-64167896 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min,1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) T1/2 is the apparent terminal elimination half-life, calculated as 0.693/Lambda(z).
Elimination Rate Constant (Lambda[z]) of JNJ 64167896 (Metabolite of JNJ-64041575) Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 to 3 months) Lambda\[z\] is the apparent terminal elimination rate constant, estimated by linear regression using the terminal logarithmic (log)-linear phase of the log-transformed concentration vs time data.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Up to end of study (approximately 6 months) An adverse event (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.
Trial Locations
- Locations (1)
Clinical Pharmacology Unit
🇧🇪Merksem, Belgium