To access the safety, tolerability, pharmacokinetics and pharmacodynamics of subcutaneously administered ATRA-2002 against commercially available oral formulation of abiraterone acetate in healthy male adults
The study will be conducted in 4 dosing groups of 8 subjects each. Thirty-two healthy adult men will be randomly assigned to a treatment cohort and will receive either a single Subcutaneous (SC) dose of ATRS-2002 (abiraterone acetate), or a single oral dose of the commercially available formulation of abiraterone acetate (Zytiga®). Additionally, for Cohorts 1 through 3, a single subject will be randomized as a sentinel subject to be dosed at least 24 hours prior to the rest of cohort (ROC). Dosing in the abiraterone acetate SC cohorts will be sequential and will start with subjects in the lowest SC dosing cohort (i.e., 25 mg). Dosing will not begin in the next highest SC dose cohort until all safety data, as well as available PK (Pharmacokinetic) data and TT levels, from the previous cohort(s) have been reviewed by the safety review committee (SRC e.g., Sponsor and Investigator) and it has been deemed safe to proceed to the next highest dose. Dosing in the oral abiraterone acetate cohort (Cohort 4) may begin at any time during the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
ATRS-2002
Pharmacokinetic assessment
Peak concentration (CMAX)
Time frame: Pre-dose (within 30 minutes), Post dose - 4hours, 8hours, 12hours on day 1 and then 24hours, 36hours, 48hours, 60hours, 72hours, 84hours, 96hours, 168hours, 240hours, 336hours, 504hours, 672hours
Pharmacodynamic assessment
To determine TT (total testosterone) and LH (luteinizing hormone) levels from whole blood
Time frame: Pre-dose (within 30 minutes), Post dose - 4hours, 8hours, 12hours on day 1 and then 24hours, 36hours, 48hours, 60hours, 72hours, 84hours, 96hours, 168hours, 240hours, 336hours, 504hours, 672hours
Safety assessment
Normal 12-Lead ECG
Time frame: Screening (Days -28 to -2), Day -1 and Days 1,3,5 and 15
Safety assessment
Abnormal Blood pressure
Time frame: Screening (Days -28 to -2), Predose - 4 hours, 8 hours, 12 hours, 24hours, 36hours, 48 hours, 72 hours and 96 hours. Vital signs will also be measured on Day 8, 11, 15, 22 and 29.
Safety assessment
Abnormal Heart rate and respiratory rate
Time frame: Screening (Days -28 to -2), Predose - 4 hours, 8 hours, 12 hours, 24hours, 36hours, 48 hours, 72 hours and 96 hours. Vital signs will also be measured on Day 8, 11, 15, 22 and 29.
Safety assessment
Abnormal Tympanic temperature
Time frame: Screening (Days -28 to -2), Predose - 4 hours, 8 hours, 12 hours, 24hours, 36hours, 48 hours, 72 hours and 96 hours. Vital signs will also be measured on Day 8, 11, 15, 22 and 29.
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Safety assessment
Abnormal Lab tests-Hematology (Hemoglobin, hematocrit, platelets, red blood cells, white blood cells and differential)
Time frame: Screening (Days -28 to -2), Day -1, Day 3, Day 8, Day15 and Day 29
Safety assessment
Abnormal Lab tests-Serum Chemistry (Urea, glucose, creatinine, sodium, potassium, chloride, bicarbonate, total protein, albumin, AST, ALT, alkaline phosphatase, total bilirubin, direct bilirubin, AM cortisol, lipid profile (screening only))
Time frame: Screening (Days -28 to -2), Day -1 and Days 3, 5, 8, 11, 15, 22, and Day 29
Safety assessment
Abnormal Lab tests-PSA (Prostate specific antigen)
Time frame: Screening (Days -28 to -2) and Day 29
Safety assessment
Abnormal Lab tests-Urinalysis (Color, clarity/turbidity, pH, specific gravity, glucose, ketones, nitrite, leukocyte esterase, microscopy)
Time frame: Screening (Days -28 to -2), Day -1, Day 3, Day 5, Day 15, Day 29
Local tolerability
Inspection of injection site for local reactions including erythema, edema, blistering, peeling skin, and rash)
Time frame: Pre-dose, post dose-4 hours, 8hours, 12hours, 24hours, 36hours, 48hours, 72hours and 96 hours. Inspection will also be done at FU visits on Day 8, 11,15, 22 and 29
Local tolerability
Pain intensity (11-point numeric pain rating scale (NPRS: 0-10) where 0=no pain and 10=the worst pain imaginable)
Time frame: Immediately after SC dosing on day 1, 4, 8, 12, 24, 36, 48, 60, 72 and 96 hrs post dose. On day 8-to measure pain 11-point numeric pain rating scale will be used