A Study to Assess Effects of Clarithromycin on Pharmacokinetics of JNJ-54861911 in Healthy Male Participants

NCT02197884 | Completed Phase 1

• 3 other identifiers: CR1047632014-001793-3354861911ALZ1009
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effects of strong cytochrome P450 (CYP) 3A4 inhibitors (Itraconazole and Clarithromycin), on pharmacokinetics (PK) (study of the way a drug enters and leaves the blood and tissues over time) of single dose of JNJ-54861911 in healthy male participants.

Conditions

Healthy

Keywords

Healthy; JNJ-54861911; Cytochrome P450 3A4 inhibitor; Itraconazole; Clarithromycin; Alzheimer's disease

Outcome Measures

Primary Outcomes (8)

• Maximum Observed Plasma Concentration (Cmax) of JNJ-54861911 and diaminothiazine (DIAT)

  The Cmax is the maximum observed plasma concentration.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9

• Time to Reach Maximum Concentration (Tmax) of JNJ-54861911 and DIAT

  The Tmax is time to reach the maximum observed plasma concentration.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9

• Time to Last Quantifiable Plasma Concentration (Tlast) of JNJ-54861911 and DIAT

  The Tlast is time to last observed quantifiable plasma concentration (Clast).

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9

• Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of JNJ-54861911 and DIAT

  The AUC (0-last) is area under the plasma concentration-time curve from time zero to time of last quantifiable concentration.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9

• Area Under the Plasma Concentration-time Curve From Time Zero to Extrapolated Infinite Time (AUC [0-infinity]) of JNJ-54861911 and DIAT

  The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to extrapolated infinite time, calculated as the sum of AUC (0-last) and Clast/lambda(z), where AUC (0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time; Clast is the last observed quantifiable concentration; and lambda(z) is first-order rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9

• Area Under the Plasma Concentration-time Curve From Time Zero to Time 24 Hours (AUC [0-24]) of JNJ-54861911 and DIAT

  Area under the plasma concentration-time curve from time zero to time 24 hours.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9

• Elimination Half-Life (t1/2) of JNJ-54861911 and DIAT

  Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve, is calculated as 0.693 divided by lambda(z), where lambda(z) is first-order rate constant associated with the terminal portion of the curve. The t1/2 is the measure of time, for plasma concentration to decrease by one half.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9

• Elimination Rate Constant (lambda[z]) of JNJ-54861911 and DIAT

  Lambda(z) is first-order elimination rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 18, 24, 36, 48, 72, 96 hours post-dose on Day 1 and 9

Secondary Outcomes (1)

• Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

  Screening up to follow-up (7 to 14 days after last dose administration)

Study Arms (2)

Itraconazole + JNJ-54861911 (Part 1)

EXPERIMENTAL

Single dose of JNJ-54861911, 25 milligram (mg) tablet orally on Day 1 and Day 9 along with itraconazole 200 mg (2\*100 mg capsule) orally once daily from Day 5 to Day 12.

Drug: JNJ-54861911, 25 mg; Drug: Itraconazole 200 mg

Clarithromycin + JNJ-54861911 (Part 2)

EXPERIMENTAL

Single dose of JNJ-54861911, 25 mg tablet orally on Day 1 and Day 9 along with clarithromycin 500 mg immediate release tablet orally twice daily from Day 5 to Day 12.

Drug: JNJ-54861911, 25 mg; Drug: Clarithromycin 500 mg

Interventions

JNJ-54861911, 25 mg DRUG

JNJ-54861911, 25 mg tablet orally on Day 1 and Day 9.

Clarithromycin + JNJ-54861911 (Part 2); Itraconazole + JNJ-54861911 (Part 1)

Itraconazole 200 mg DRUG

Itraconazole 200 mg (2\*100 mg capsule) orally once daily from Day 5 to Day 12.

Itraconazole + JNJ-54861911 (Part 1)

Clarithromycin 500 mg DRUG

Clarithromycin 500 mg immediate release tablet orally twice daily from Day 5 to Day 12.

Clarithromycin + JNJ-54861911 (Part 2)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed an informed consent document indicating they understand the purpose of and procedures required for the study, and are willing to participate in the study
• Body mass index between 18 and 30 kilogram per square meter
• Must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening or admission (up to Day 1 predose)
• Man, who is sexually active with a woman of child-bearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the investigator, and must also agree to not donate sperm during the study and for 90 days after receiving the study drug
• Participant must be healthy on the basis of clinical laboratory tests performed at Screening and/or admission and as per investigator's judgment

You may not qualify if:

• History of or current liver or renal impairment, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, dermatological or metabolic disturbances
• Known allergies, hypersensitivity, or intolerance to JNJ-54861911 or its excipients, itraconazole (Part 1 only) or clarithromycin (Part 2 only)
• History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
• History of drug or alcohol abuse within 6 months before Screening or positive test result(s) for alcohol and/or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines, benzodiazepines and cotinine) at Screening or admission
• Smoking of cigarettes (or equivalent) and/or used nicotine based products within 3 months prior to study drug administration

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Merksem, Belgium

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

atabecestat; Itraconazole; Clarithromycin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: July 23, 2014
• Study Start: July 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 15, 2014

Record last verified: 2014-10

Locations

BE (1)