First in Man Clinical Trial of Emodepside (BAY 44-4400)

A Phase 1, Blinded, Randomized, Placebo Controlled, Parallel-Group, Single-Dose, Dose-Escalation Study to Investigate Safety, Tolerability, and Pharmacokinetics of Emodepside (BAY 44-4400) After Oral Dosing in Healthy Male Subjects

This study will investigate the safety, tolerability, and pharmacokinetics of single ascending doses of emodepside (BAY 44-4400) in healthy male volunteers. This study will also conduct an exploratory investigation of the relative bioavailability of emodepside administered as tablets and determine the effect of food on the pharmacokinetics.

Inclusion Criteria:

• Male, Caucasian volunteers, deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine. Optionally, after further evaluation during the study, at the sponsor's discretion other ethnic groups may be recruited.
• Aged 18 to 55 years.
• With a body mass index (BMI; Quetelet index) in the range of 18 to 30.1 kg/m2 at screening.
• Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
• Willingness to give written consent to participate, after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate

Exclusion Criteria:

• Participation in another clinical trial within 3 months prior and during the study, or 5-times the half-life of the drug tested in the previous clinical trial, whichever is longer (time calculated relative to the last dose in the previous clinical trial)
• Clinically relevant abnormal medical history, concurrent medical condition, acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the trial or make it unnecessarily hazardous.
• Surgery (eg stomach bypass) or medical condition that might affect absorption of study drug taken orally.
• Presence of abnormal physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
• Positive tests for hepatitis B & C, HIV
• Presence or history of drug or alcohol abuse during the last 10 years, or intake of more than 21 units of alcohol weekly.
• Regular daily consumption of more than one liter of xanthine-containing beverages
• Regular daily consumption of more than 5 cigarettes daily, or use more than 3 grams (1/8 ounce) of tobacco
• Use of a prescription medicine during the 28 days before the first dose of trial medication or use of an over-the-counter medicine, with the exception of acetaminophen (paracetamol), during the 7 days before the first dose of trial medication
• Use of dietary supplements or herbal remedies (such as St John's Wort) known to interfere with the CYP3A4 and/or P-gp metabolic pathways during the 28 days before the first dose of trial medication (see list in Study Procedures Manual)

Additional exclusion criteria for cohort with ophthalmological assessments:

• No contact lenses wear within 1 month prior to first dose of IMP. Contact lenses wear is not permitted during the study
• Any ocular disorder for which topical ocular therapy is currently or chronically prescribed, including inflammatory eye disease (dry eye allergic conjunctivitis [seasonal allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis], uveitis and glaucoma)
• Past history of ocular disease requiring ongoing treatment
• Past ocular surgery including laser or other refractive corneal surgery
• Evidence of eye irritation, visual difficulties, corneal opacity, ocular surface (corneal or conjunctival damage, with or without ocular symptoms)
• Evidence of narrow anterior chamber angles causing increased risk of acute glaucoma
• Evidence of ocular media opacity including lens opacity/vitreous opacities
• Evidence of retinal or optic nerve pathology
• Evidence of pronounced colour blindness, as indicated by an Ishihara score of 9/13 or below