This is an integrated Phase 1, single centre, 2-part, open-label, dose-escalation study conducted in healthy volunteers to assess the safety, tolerability, and PK of APL-1501 ER capsules in comparison to APL-1202 IR tablets.
The study will have 2 parts: Each study part will comprise 2 dosing periods with a 72-hour washout period in between: Period 1: APL-1202 IR tablet dosing and Period 2: APL-1501 ER capsule dosing. In Part A dosing will be single day/single dosing for the APL-1202 IR tablets, and single day/single dosing the APL-1501 ER capsules with 24 participants in 3 sequential cohorts, Cohorts A1, A2, and A3. Each cohort will enrol 8 participants, with male to female participants in a 1:1 ratio. In Period 1/Day 1, participants in all cohorts will be dosed with single dose of 375 mg APL-1202 IR tablets which will followed by a washout period of at least 72 hours, after which participants will be dosed with single dose of APL-1501 ER capsules in Period 2/Day 4, . In Part B dosing will be multi-day/TID dosing for the APL-1202 IR tablets, and multi-day/BID dosing the APL-1501 ER capsules with 24 participants in 2 sequential cohorts, Cohorts B1 and B2. Each cohort will enrol 12 participants, with male to female participants in a 1:1 ratio and in each of the 2 study periods, participants will be administered IP for 5 days. In period 1, participants will administered with APL-1202 IR tablet (TID) on Day 1, Day 2, Day 3, Day 4, and Day 5 and period 2 with APL-1501 ER capsule (BID) dosing on Day 9, Day 10, Day 11, Day 12, and morning of Day 13.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Period 1 drug adminstration (APL-1202 IR tablet , single dose of 375mg will be administered orally on Day 1; washout period of 72 hrs; Period 2 drug administration (APL-1501 ER capsules of 764mg, 1146 mg and 1528 mg will be administered as single dose on Day 4.
Period 1 drug adminstration (APL-1202 IR of 375mg will be administered thrice a day (TID) orally from Day 1 to Day 5; washout period of 72 hrs; Period 2 drug administration (APL-1501 ER capsules of 764mg, 1146 mg and 1528 mg will be administered twice daily (BID) from Day 9 to 13.
Nucleus Network Pty Ltd
Melbourne, Victoria, Australia
Adverse Events (AEs)
Number of participants with AEs
Time frame: Part A: upto Day 11 post dose follow up; Part B: Upto Day 20 post dose follow up
Serious Adverse Events (SAEs)
Number of participants with SAEs
Time frame: Part A: upto Day 11 post dose follow up; Part B: Upto Day 20 post dose follow up
Treatement Emergent Adverse Events (TEAEs)
Number of participants with TEAEs
Time frame: Part A: upto Day 11 post dose follow up; Part B: Upto Day 20 post dose follow up
PK parameters: area under the curve (AUC)
Area under the curve (AUC) of APL-1501 ER capsules and APL-1202 IR Tablets
Time frame: up to 120 hours post dose in each treatment period
PK parameters: maximum concentration (Cmax)
maximum concentration (Cmax), of APL-1501 ER capsules and APL-1202 IR Tablets
Time frame: up to 120 hours post dose in each treatment period
PK parameters: Tmax
Tmax of APL-1501 ER capsules and APL-1202 IR Tablets
Time frame: up to 120 hours post dose in each treatment period
PK parameters: half-life (t1/2)
apparent t1/2 of APL-1501 ER capsules and APL-1202 IR Tablets
Time frame: up to 120 hours post dose in each treatment period
Urine PK parameters: Renal clearance (CLr)
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Urine concentration of APL-1202 Tablets.
Time frame: up to 120 hours post dose in each treatment period
Urine PK parameters: Total amount of the APL-1202 excreted in urine from time t1 to t2 hours (Aet1-t2)
Urine concentration of APL-1202 Tablets.
Time frame: up to 120 hours post dose in each treatment period
PK Parameters: Apparent total plasma clearance (CL/F)
CL/F of APL-1501 ER capsules and APL-1202 IR Tablets
Time frame: up to 120 hours post dose in each treatment period
PK Parameters: Apparent terminal volume of distribution (Vz/F)
Vz/F of APL-1501 ER capsules and APL-1202 IR Tablets
Time frame: up to 120 hours post dose in each treatment period