A Study to Evaluate Bioavailability, Food Effect, Safety and Tolerability of a Solid Dosage Formulation of JNJ-54861911 in Healthy Older Male Participants

NCT02260700 | Completed Phase 1

• 3 other identifiers: CR10238054861911ALZ10032013-002650-70
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) and the relative-bioavailability (the extent to which a drug or other substance becomes available to the body) of JNJ-54861911 solid dosage formulation compared with JNJ 54861911 oral suspension formulation in healthy older male participants.

Conditions

Healthy

Keywords

Healthy; Bioavailability; Alzheimer's Disease; JNJ-54861911

Outcome Measures

Primary Outcomes (9)

• Maximum Plasma Concentration (Cmax) of JNJ-54861911

  The Cmax is the maximum observed plasma concentration of JNJ-54861911.

  Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose on Day 1 of each period

• Time to Reach the Maximum Plasma Concentration (Tmax) of JNJ-54861911

  The Tmax is the time to reach the maximum observed plasma concentration of JNJ-54861911.

  Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose on Day 1 of each period

• Area Under the Plasma Concentration-Time Curve From 0 to t Hours (AUC[0-t]) Post Dose of JNJ-54861911

  The AUC (0-t) calculated by trapezoidal summation \[time t is the time of the last quantifiable concentration (C\[last\])\].

  Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose on Day 1 of each period

• Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of JNJ-54861911

  The AUC (0-infinity) is the area under the plasma JNJ-54861911concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma JNJ-54861911 concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.

  Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose on Day 1 of each period

• Elimination Rate Constant (Lambda [z]) of JNJ-54861911

  The Lambda (z) determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve.

  Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose on Day 1 of each period

• Terminal Half-life (t[1/2]) of JNJ-54861911

  The t(1/2) is defined as 0.693/Lambda (z).

  Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose on Day 1 of each period

• Relative Bioavailability (F[rel]) of JNJ-54861911

  Relative bioavailability, calculated as individual Cmax and AUC treatment ratios (for the comparison of food effect).

  Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose on Day 1 of each period

• Rate of Absorption of JNJ-54861911

  Rate of absorption will be measured using the peak concentration of JNJ-54861911 (following administration of solid dosage form and suspension dosage form) under fasted conditions and fed conditions.

  Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose on Day 1 of each period

• Extent of Absorption of JNJ-54861911

  Extent of absorption will be measured under fasted conditions and fed conditions, using the area under plasma concentrations of JNJ-54861911 versus time from time 0 to the last sample point (AUC\[0-t\]) and from time 0 to infinity (AUC\[0-inf\]).

  Pre-dose; 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose on Day 1 of each period

Secondary Outcomes (1)

• Number of Participants with Adverse Events (AEs) and Serious AEs

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

Study Arms (6)

Sequence 1 (ABC)

EXPERIMENTAL

Participants will receive Treatment A (single dose of JNJ-54861911 25 milligram (mg) oral suspension formulation under fasted conditions) in Period 1; followed by Treatment B (single oral dose of JNJ-54861911 25 mg solid formulation under fasted conditions) in Period 2; followed by Treatment C (single oral dose of JNJ-54861911 25 mg solid formulation under fed conditions) in Period 3. A washout period of at least 6 days will be maintained between each treatment period.

Drug: JNJ-54861911 (Treatment A); Drug: JNJ-54861911 (Treatment B); Drug: JNJ-54861911 (Treatment C)

Sequence 2 (ACB)

EXPERIMENTAL

Participants will receive Treatment A (single dose of JNJ-54861911 25 milligram (mg) oral suspension formulation under fasted conditions) in Period 1; followed by Treatment C (single oral dose of JNJ-54861911 25 mg solid formulation under fed conditions) in Period 2; followed by Treatment B (single oral dose of JNJ-54861911 25 mg solid formulation under fasted conditions) in Period 3. A washout period of at least 6 days will be maintained between each treatment period.

Drug: JNJ-54861911 (Treatment A); Drug: JNJ-54861911 (Treatment B); Drug: JNJ-54861911 (Treatment C)

Sequence 3 (BAC)

EXPERIMENTAL

Participants will receive Treatment B (single dose of JNJ-54861911 25 mg solid formulation under fasted conditions) in Period 1; followed by Treatment A (single oral dose of JNJ-54861911 25 milligram (mg) oral suspension formulation under fasted conditions) in Period 2; followed by Treatment C (single oral dose of JNJ-54861911 25 mg solid formulation under fed conditions) in Period 3. A washout period of at least 6 days will be maintained between each treatment period.

Drug: JNJ-54861911 (Treatment A); Drug: JNJ-54861911 (Treatment B); Drug: JNJ-54861911 (Treatment C)

Sequence 4 (BCA)

EXPERIMENTAL

Participants will receive Treatment B (single dose of JNJ-54861911 25 mg solid formulation under fasted conditions) in Period 1; followed byTreatment C (single dose of JNJ-54861911 25 mg solid formulation under fed conditions) in Period 2; followed by Treatment A (single dose of JNJ-54861911 25 milligram (mg) oral suspension formulation under fasted conditions) in Period 3. A washout period of at least 6 days will be maintained between each treatment period.

Drug: JNJ-54861911 (Treatment A); Drug: JNJ-54861911 (Treatment B); Drug: JNJ-54861911 (Treatment C)

Sequence 5 (CAB)

EXPERIMENTAL

Participants will receive Treatment C (single dose of JNJ-54861911 25 mg solid formulation under fed conditions) in Period 1; followed by Treatment A (single dose of JNJ-54861911 25 milligram (mg) oral suspension formulation under fasted conditions) in Period 2; followed by Treatment B (single dose of JNJ-54861911 25 mg solid formulation under fasted conditions) in Period 3. A washout period of at least 6 days will be maintained between each treatment period.

Drug: JNJ-54861911 (Treatment A); Drug: JNJ-54861911 (Treatment B); Drug: JNJ-54861911 (Treatment C)

Sequence 6 (CBA)

EXPERIMENTAL

Participants will receive Treatment C (single dose of JNJ-54861911 25 mg solid formulation under fed conditions) in Period 1; followed by Treatment B (single dose of JNJ-54861911 25 mg solid formulation under fasted conditions) in Period 2; followed by Treatment A (single dose of JNJ-54861911 25 milligram (mg) oral suspension formulation under fasted conditions) in Period 3. A washout period of at least 6 days will be maintained between each treatment period.

Drug: JNJ-54861911 (Treatment A); Drug: JNJ-54861911 (Treatment B); Drug: JNJ-54861911 (Treatment C)

Interventions

JNJ-54861911 (Treatment A) DRUG

Participants will receive a single oral 25 mg dose of JNJ-54861911 as Treatment A (oral suspension formulation) under fasted conditions in one of the treatment periods.

Sequence 1 (ABC); Sequence 2 (ACB); Sequence 3 (BAC); Sequence 4 (BCA); Sequence 5 (CAB); Sequence 6 (CBA)

JNJ-54861911 (Treatment B) DRUG

Participants will receive a single oral 25 mg dose of JNJ-54861911 as Treatment B (solid formulation) under fasted conditions in one of the treatment periods.

Sequence 1 (ABC); Sequence 2 (ACB); Sequence 3 (BAC); Sequence 4 (BCA); Sequence 5 (CAB); Sequence 6 (CBA)

JNJ-54861911 (Treatment C) DRUG

Participants will receive a single oral 25 mg dose of JNJ-54861911 as Treatment C (solid formulation) under fed conditions in one of the treatment periods.

Sequence 1 (ABC); Sequence 2 (ACB); Sequence 3 (BAC); Sequence 4 (BCA); Sequence 5 (CAB); Sequence 6 (CBA)

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body mass index (BMI; weight \[kilogram(kg)\]/height\^2 \[meter square (m\^2)\]) between 18 and 30 kg/m\^2, (inclusive)
• Be healthy for their age group with or without medication on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening or admission. Minor deviations in ECG, which are not considered to be of clinical significance to the investigator, are acceptable
• Be healthy on the basis of clinical laboratory tests performed at Screening. If the results of the serum chemistry panel \[including liver enzymes\], hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participants' source documents and initialed by the investigator
• Men who are sexually active with a woman of childbearing potential and have not had a vasectomy must agree to use a barrier method of birth control for example, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, their female partners should also use an appropriate method of birth control for at least the same duration
• Participants' must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

You may not qualify if:

• Participant has a clinically significant abnormal physical examination, vital signs or 12 lead ECG (including QTc greater than (\>) 450msec, Left Bundle Branch Block, permanent pacemaker or implantable cardioverter defibrillator) at Screening or admission
• Participant has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
• Use of any prescription or over-the-counter medication, herbal medication, vitamins, or mineral supplements within 14 days prior to study drug administration (not including paracetamol). Medication for chronic use in age related disease will be allowed after approval by both the investigator and to the sponsor. No change in dose or regimen will be permitted during the study that is, from the Screening visit until the follow-up visit
• Participant has a history of spontaneous, prolonged or severe bleeding of unclear origin
• Participant has a history of epilepsy or fits or unexplained black-outs other than vasovagal collapse

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Merksem, Belgium

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

atabecestat

Condition Hierarchy (Ancestors)

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

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: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2014
• First Posted: October 9, 2014
• Study Start: September 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: October 9, 2014

Record last verified: 2014-10

Locations

BE (1)