A Randomized, Placebo- and Comparator-controlled, Double-blind, Multiple (Ascending)
Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and
Pharmacodynamics of JNJ-54175446 in Healthy Male Subjects

1. Healthy male subjects between 18 and 55 years of age, inclusive.
2. A body mass index (BMI) between 18 and 32 kg/m2, inclusive
3. Healthy on the basis of physical examination, medical history, vital signs, and 12-lead ECG [incl. QTcF <= 450ms (triplicate ECG)] performed at screening and admission to the clinical unit. Minor abnormalities in ECG, which are not considered to be of clinical significance by the investigator, are acceptable.
4. Healthy on the basis of clinical laboratory tests performed at screening.
5. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control. Subjects must also not donate sperm during the study and for 3 months after receiving the last dose of study drug.
6. Agree to reside in the clinical unit for minimally 15 days during the double blind treatment period.
7. Subjects must be willing to adhere to the prohibitions and restrictions specified in the protocol.
8. Each included subject must have signed an informed consent form (ICF)

1. A history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the subject.
2. A clinically significant (history of) psychiatric illnesses or (history of) psychotic symptoms
3. A family history of relevant psychiatric disorders (first degree) and/or psychotic disorders (first and second degree)
4. A liver function test (including ALT, AST, GGT, ALP and bilirubin) at screening exceeding the ULN.
5. A history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening.
6. A history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening.
7. A PT and/or an aPTT exceeding the ULN.
8 An International Normalized Ratio (INR; [prothrombintest / prothrombincontrol]ISI) >2.
9. A history of malignancy within 5 years before screening (with certain exceptions)
10. A history of drug or alcohol use disorder (mild or greater) according to DSM criteria within 5 years before Screening. Or a positive test result(s) for alcohol and/or drugs of abuse (including: opiates (including methadone), cocaine, amphetamines (screening only) and methamphetamines (screening only), MDMA (screening only), cannabinoids, and benzodiazepines) at screening or admission to the clinical unit.
11. Drinks, on average, more than 8 cups of tea/coffee/cocoa/cola/caffeinated beverages (e.g., energy drink) per day.
12. A clinically significant acute illness within 7 days prior to study drug administration.
13. Smokes cigarettes (or equivalent) and/or has used nicotine based products within 3 months prior to study drug administration.
14. A man who plans to father a child while enrolled in this study or within 90 days after the last dose of study drug.
15. A history of clinically significant drug and/or food allergies.
16. Known allergies, hypersensitivity, or intolerance to JNJ-54175446, AMPH or minocycline or one of their excipients.
17. Contraindications to the use of minocycline or AMPH.
18. Taken any disallowed therapies (protocol Section 8)
19. Received an investigational drug (including vaccines) or used an IMD within 90 days before the planned start of study.
20. Had major surgery, (e.g., requiring general anesthesia) within 8 weeks before screening, or will have within 4 weeks after the last dose.
21. Donated one or more units (approximately 450 mL) of blood or acute loss of an equivalent amount of blood within 90 days prior to study drug administration
22. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
23. Psychological and/or emotional problems, which would render the informed consent invalid, or limit the ability of the subject to comply with the study requirements.
24. Vulnerable subjects (e.g., a person kept in detention or a person under guardianship).
25. Unable to read and understand the consent forms, complete study-related procedures, and/or communicate with the study staff.
26. An employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.