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

NCT03468777 | Terminated Phase 1

• 3 other identifiers: CR1084372017-004832-1264041575RSV1010
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (8)

• Observed Plasma Concentration at 12 Hours Post dose (C12h) of JNJ-63549109 (Metabolite of JNJ- 64041575)

  C12h is observed plasma concentration at 12 hours post dose.

  12 hours postdose (Day 1)

• Observed Plasma Concentration at 24 Hours Post dose (C24h) of JNJ-63549109 (Metabolite of JNJ- 64041575)

  C24h is observed plasma concentration at 24 hours post dose.

  24 hours postdose (Day 2)

• Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of JNJ- 64041575)

  Cmax is the maximum observed plasma concentration.

  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)

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-63549109 (Metabolite of JNJ-64041575)

  Tmax is the actual sampling time to reach maximum observed plasma concentration.

  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)

• Area Under Plasma Concentration Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of JNJ-63549109 (Metabolite of JNJ-64041575)

  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.

  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 From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-63549109 (Metabolite of JNJ-64041575)

  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.

  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)

• Elimination Half-Life (T1/2) of JNJ-63549109 (Metabolite of JNJ-64041575)

  T1/2 is the apparent terminal elimination half-life, calculated as 0.693/Lambda(z).

  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)

• Elimination Rate Constant (Lambda[z]) of JNJ-63549109 (Metabolite of JNJ-64041575)

  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.

  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)

Secondary Outcomes (9)

• Observed Plasma Concentration at 12 Hours Post dose (C12h) of JNJ-64167896 (Metabolite of JNJ- 64041575)

  12 hours postdose (Day 1)

• Observed Plasma Concentration at 24 Hours Post dose (C24h) of JNJ-64167896 (Metabolite of JNJ- 64041575)

  24 hours postdose (Day 2)

• 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)

• 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)

• 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)

Study Arms (8)

Part 1: Treatment Sequence (ABC)

EXPERIMENTAL

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.

Drug: Lumicitabine; Drug: Lansoprazole; Drug: Ranitidine

Part 1: Treatment Sequence (BAC)

EXPERIMENTAL

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.

Drug: Lumicitabine; Drug: Lansoprazole; Drug: Ranitidine

Optional Part 3: Treatment Sequence (DEF)

EXPERIMENTAL

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.

Drug: Lumicitabine; Drug: Lansoprazole; Drug: Ranitidine

Optional Part 3: Treatment Sequence (EFD)

EXPERIMENTAL

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.

Drug: Lumicitabine; Drug: Lansoprazole; Drug: Ranitidine

Optional Part 3: Treatment Sequence (FDE)

EXPERIMENTAL

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.

Drug: Lumicitabine; Drug: Lansoprazole; Drug: Ranitidine

Optional Part 3: Treatment Sequence (FED)

EXPERIMENTAL

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.

Drug: Lumicitabine; Drug: Ranitidine

Optional Part 3: Treatment Sequence (EDF)

EXPERIMENTAL

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.

Drug: Lumicitabine; Drug: Lansoprazole; Drug: Ranitidine

Optional Part 3: Treatment Sequence (DFE)

EXPERIMENTAL

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.

Drug: Lumicitabine; Drug: Lansoprazole; Drug: Ranitidine

Interventions

Lumicitabine DRUG

Participants will receive single oral dose of 1000 mg lumicitabine as per assigned treatment sequence.

Also known as: JNJ-64041575, ALS-008176

Optional Part 3: Treatment Sequence (DEF); Optional Part 3: Treatment Sequence (DFE); Optional Part 3: Treatment Sequence (EDF); Optional Part 3: Treatment Sequence (EFD); Optional Part 3: Treatment Sequence (FDE); Optional Part 3: Treatment Sequence (FED); Part 1: Treatment Sequence (ABC); Part 1: Treatment Sequence (BAC)

Lansoprazole DRUG

Participants will receive single oral dose of 30 mg lansoprazole capsule as per assigned treatment sequence.

Optional Part 3: Treatment Sequence (DEF); Optional Part 3: Treatment Sequence (DFE); Optional Part 3: Treatment Sequence (EDF); Optional Part 3: Treatment Sequence (EFD); Optional Part 3: Treatment Sequence (FDE); Part 1: Treatment Sequence (ABC); Part 1: Treatment Sequence (BAC)

Ranitidine DRUG

Participants will receive single oral dose of 150 mg ranitidine as per assigned treatment sequence.

Optional Part 3: Treatment Sequence (DEF); Optional Part 3: Treatment Sequence (DFE); Optional Part 3: Treatment Sequence (EDF); Optional Part 3: Treatment Sequence (EFD); Optional Part 3: Treatment Sequence (FDE); Optional Part 3: Treatment Sequence (FED); Part 1: Treatment Sequence (ABC); Part 1: Treatment Sequence (BAC)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine; Lansoprazole; Ranitidine

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Furans

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: March 19, 2018
• Study Start: March 6, 2018
• Primary Completion: July 9, 2018
• Study Completion: July 9, 2018
• Last Updated: July 23, 2018

Record last verified: 2018-07

Locations

BE (1)