This is a randomized, double-blind, placebo-controlled, multiple ascending dose study conducted at one study center in Switzerland. Four (4) panels (A, B, C and D) of 8 male subjects (6 active and 2 placebo) each receiving multiple doses of PBTZ169 or a matching placebo, at increasing dose levels, once or twice daily. Subjects will participate in only one panel. Blocks of 4 subjects (3 under active treatment, 1 under placebo) will be investigated in parallel. Panels will start sequentially. Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and PK assessment of PBTZ169. Dose escalation will be allowed once the Trial Safety Board has determined that adequate safety and tolerability after each panel completion has been demonstrated to permit proceeding to the next panel. In addition, a preliminary assessment of the drug interaction potential of PBTZ169 will be done by the measurement of inhibition or induction of human cytochromes through the metabolism of microdoses of standard probe substrates
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
32
PBTZ169 crystalline supplied as powder for oral solution
matching placebo supplied as powder for oral solution
Division of Clinical Pharmacology, Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, Canton of Vaud, Switzerland
Safety and tolerability of increasing multiple oral doses of PBTZ169 in healthy male adult subjects evaluated by Treatment Emergent Adverse Events (TEAEs).
Evaluation by thorough monitoring of Treatment Emergent Adverse Events (TEAEs) following doses of PBTZ169 crystalline or placebo
Time frame: Days 0-17
Relative oral bioavailability assessment of PBTZ169 in healthy male subjects after multiple dosing
Estimation from the ratio of area under plasma concentration curves (AUCs) determined after the administration of PBTZ169
Time frame: Days 0-17
Pharmacokinetics (PK) of multiple oral doses of PBTZ169 using Cmax
Determination of non-compartmental PK parameter Maximum Plasma Concentration \[Cmax\] after determination of the amount of the parent compound and its known metabolites in plasma samples
Time frame: Days 0-17
Pharmacokinetics (PK) of multiple oral doses of PBTZ169 using Tmax
Determination of non-compartmental PK parameter Time of maximum observed Plasma Concentration \[Tmax\] after determination of the amount of the parent compound and its known metabolites in plasma samples
Time frame: Days 0-17
Metabolism interaction of multiple oral doses of PBTZ169 by measuring ratios of 7 probe substrates before the first and and after the last dose
Measurement of the ratios of 7 probe of known substrates of human Cytochome P-450 enzyme family before the first and and after the last dose
Time frame: Days -1 to 14
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