The purpose of this study is to assess the effects of single and multiple once daily doses of 50 milligram (mg) of JNJ-54861911 on pharmacokinetics (PK) (study of the way a drug enters and leaves the blood and tissues over time) of caffeine, midazolam, and tolbutamide in healthy male participants.

This is a single-center, open-label (participants and researchers are aware about the treatment, participants are receiving), fixed-sequence study in healthy male participants. The study consists of 3 phases: Screening Phase (within 21 to 2 days prior to the first dose administration on Day 1), Open Label Treatment Phase (Day 1 up to Day 9), and Follow-up Phase (7 to 14 days after discharge from the study unit on Day 10 or at early withdrawal). The maximum duration of study will be 7 weeks per participant. During the Open-Label Treatment Phase, participants will receive JNJ-54861911, 50 mg (2*25 mg tablets) orally once daily from Day 2 to Day 9 along with caffeine 100 mg (2*50 mg tablets), midazolam 2 mg (1 milliliter [mL], 2 mg/mL solution), and tolbutamide 500 mg tablet, orally on Day 1, 2, and 9. Blood samples will be collected pre-dose (Day 1) up to Day 10 to understand the PK characteristics of midazolam, 1-hydroxy midazolam (midazolam metabolite), caffeine, paraxanthine (caffeine metabolite), tolbutamide, 4-hydroxytolbutamide and carboxytolbutamide (tolbutamide metabolites). In addition, a blood sample will be collected on Day -1 from all enrolled participants to study genetic factors that may influence the PK, safety, and/or tolerability of JNJ-54861911 and co-medications. Participants' safety will be monitored throughout the study.

Inclusion Criteria:

• 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 pre-dose)
• 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 last dose of study drug
• Participant must be healthy on the basis of clinical laboratory tests performed at Screening as per Investigator's judgment

Exclusion Criteria:

• History of or current liver or renal insufficiency, closed-angle glaucoma, 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, sulfonamides, midazolam, caffeine or tolbutamide.
• History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
• History of drug or alcohol abuse according to current Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria within 6 months before Screening or positive test result(s) for alcohol and/or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines, metamphetamines, 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