This is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and pharmacokinetics (PK) of escalating single ascending dose (SAD) and multiple ascending doses (MAD) of ARN-75039 when administered by the oral route in healthy adult subjects. The SAD portion of the study will enroll approximately 40 subjects for a total duration of 6 weeks. A cohort of 8 subjects in the SAD portion of the study will be selected to assess food effect (including relative bioavailability). The MAD portion of the study will enroll approximately 24 subjects for a total duration of 10 weeks.
This is a randomized, double-blind study of ARN-75039 or placebo given as single and multiple escalating doses in normal healthy subjects. The study will be conducted in three parts: Part 1 will be a Single Ascending Dose (SAD) study enrolling approximately 40 subjects for a total duration of 6 weeks. Part 2 will be a Multiple Ascending Dose (MAD) study enrolling approximately 24 subjects for a total duration of 10 weeks, and part 3 will be a selected SAD cohort in a fasted state to evaluate the effect of food on the bioavailability of ARN-75039, enrolling approximately 8 subjects from a selected SAD cohort for a duration of 6 weeks. The dose escalation will be performed in a step-wise manner. Dose escalation stopping rules will be used to determine whether or not investigation of a higher dose level will proceed per protocol. Safety and tolerability will be assessed by periodic measurement of vital signs, physical examinations, electrocardiograms, blood laboratory analyses and occurrence of adverse events (AE). PK blood samples will be collected at pre-specified time points for noncompartmental data analysis. The PK parameters include but are not limited to: Cmax, Tmax, AUC, CL, and t½. For determination of the food effect, for selected PK parameters (e.g., Cmax, AUC0-τ, and AUC0-∞), comparisons between the fed and fasted conditions will be made.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
94
SAD: Up to 5 single escalating doses MAD: Up to 3 escalating doses Food-effect: Selected single dose
Given at frequency and amounts matching ARN- 75039 dosing regimen
Spaulding Clinical, LLC
West Bend, Wisconsin, United States
The type and frequency of treatment-emergent adverse events (TEAEs)
Incidence of AEs and SAEs
Time frame: Day 1 through 14 days post dose for SAD cohorts, and 28 days post last study dose for MAD cohorts.
Determination of the recommended phase 2 dose (RP2D)
Maximum tolerated dose
Time frame: Day 1 through 14 days post dose for SAD cohorts and 28 days post last study dose for MAD cohorts.
Determine Maximum Plasma concentrations of ARN-75039
PK of ARN-75039 in health subjects as assessed by maximum plasma concentration (Cmax) towards determination of the optimal PK dose
Time frame: Day 1 through Day 8 post dose for SAD and FE cohorts, and 28 days post last study dose for MAD cohorts.
Determination of time to maximum concentration (Tmax)
PK of ARN-75039 in healthy subjects as assessed by time to maximum concentration (Tmax) towards determination of the optimal PK dose
Time frame: Day 1 through Day 8 post dose for SAD and FE cohorts, and 28 days post last study dose for MAD cohorts.
Determination of plasma exposure (AUC0-t, AUC0-inf)
PK of ARN-75039 in healthy subjects as assessed by plasma exposure (AUC0-t, AUC0-inf) determination of the optimal PK dose
Time frame: Day 1 through Day 8 post dose for SAD and FE cohorts, and 28 days post last study dose for MAD cohorts.
Determination of terminal half life
PK of ARN-75039 in healthy subjects as assessed by terminal elimination half life (t1/2) determination of the optimal PK dose
Time frame: Day 1 through Day 8 post dose for SAD and FE cohorts, and 28 days post last study dose for MAD cohorts.
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