Trial Outcomes & Findings for Safety, Tolerability and Pharmacokinetics of AM1476 in Healthy Subjects (NCT NCT04691115)

Last Updated: 2024-08-02

Results Overview

A treatment-emergent adverse-event (TEAE) was defined as an adverse event that started during or after first dosing, or started prior to first dosing and increased in severity after first dosing.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

97 participants

Primary outcome timeframe

Through study completion, an average of 7 weeks

Results posted on

2024-08-02

Participant Flow

Participant milestones

Participant milestones
Measure	Part A, Groups 1 to 9: Placebo Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
Overall Study STARTED	18	6	6	6	6	7	6	6	6	6	6	6	6	6
Overall Study COMPLETED	18	6	6	6	6	6	6	6	6	6	6	6	6	6
Overall Study NOT COMPLETED	0	0	0	0	0	1	0	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A, Groups 1 to 9: Placebo Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
Overall Study Withdrawal by Subject	0	0	0	0	0	1	0	0	0	0	0	0	0	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A, Groups 1 to 9: Placebo n=18 Participants Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=6 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg n=6 Participants Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg n=6 Participants Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg n=7 Participants Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg n=6 Participants Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg n=6 Participants Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg n=6 Participants Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg n=6 Participants Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo n=6 Participants Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD n=6 Participants Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID n=6 Participants Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID n=6 Participants Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Total n=97 Participants Total of all reporting groups
Age, Continuous	41.4 years STANDARD_DEVIATION 12.95 • n=18 Participants	42.3 years STANDARD_DEVIATION 14.56 • n=6 Participants	38.8 years STANDARD_DEVIATION 16.63 • n=6 Participants	37.0 years STANDARD_DEVIATION 14.82 • n=6 Participants	38.2 years STANDARD_DEVIATION 11.65 • n=6 Participants	28.4 years STANDARD_DEVIATION 6.21 • n=7 Participants	50.8 years STANDARD_DEVIATION 11.02 • n=6 Participants	37.0 years STANDARD_DEVIATION 13.11 • n=6 Participants	35.2 years STANDARD_DEVIATION 13.99 • n=6 Participants	38.5 years STANDARD_DEVIATION 15.87 • n=6 Participants	37.3 years STANDARD_DEVIATION 15.17 • n=6 Participants	30.7 years STANDARD_DEVIATION 8.19 • n=6 Participants	34.3 years STANDARD_DEVIATION 14.24 • n=6 Participants	28.2 years STANDARD_DEVIATION 4.17 • n=6 Participants	37.5 years STANDARD_DEVIATION 13.14 • n=97 Participants
Sex: Female, Male Female	4 Participants n=18 Participants	1 Participants n=6 Participants	3 Participants n=6 Participants	3 Participants n=6 Participants	2 Participants n=6 Participants	4 Participants n=7 Participants	3 Participants n=6 Participants	4 Participants n=6 Participants	2 Participants n=6 Participants	1 Participants n=6 Participants	2 Participants n=6 Participants	3 Participants n=6 Participants	2 Participants n=6 Participants	0 Participants n=6 Participants	34 Participants n=97 Participants
Sex: Female, Male Male	14 Participants n=18 Participants	5 Participants n=6 Participants	3 Participants n=6 Participants	3 Participants n=6 Participants	4 Participants n=6 Participants	3 Participants n=7 Participants	3 Participants n=6 Participants	2 Participants n=6 Participants	4 Participants n=6 Participants	5 Participants n=6 Participants	4 Participants n=6 Participants	3 Participants n=6 Participants	4 Participants n=6 Participants	6 Participants n=6 Participants	63 Participants n=97 Participants
Race and Ethnicity Not Collected	—	—	—	—	—	—	—	—	—	—	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United Kingdom	18 participants n=18 Participants	6 participants n=6 Participants	6 participants n=6 Participants	6 participants n=6 Participants	6 participants n=6 Participants	7 participants n=7 Participants	6 participants n=6 Participants	6 participants n=6 Participants	6 participants n=6 Participants	6 participants n=6 Participants	6 participants n=6 Participants	6 participants n=6 Participants	6 participants n=6 Participants	6 participants n=6 Participants	97 participants n=97 Participants
Height	174.3 cm STANDARD_DEVIATION 6.73 • n=18 Participants	179.2 cm STANDARD_DEVIATION 10.38 • n=6 Participants	171.0 cm STANDARD_DEVIATION 9.61 • n=6 Participants	176.9 cm STANDARD_DEVIATION 4.48 • n=6 Participants	173.3 cm STANDARD_DEVIATION 10.25 • n=6 Participants	173.3 cm STANDARD_DEVIATION 9.60 • n=7 Participants	173.7 cm STANDARD_DEVIATION 8.41 • n=6 Participants	169.3 cm STANDARD_DEVIATION 8.87 • n=6 Participants	174.2 cm STANDARD_DEVIATION 5.98 • n=6 Participants	181.3 cm STANDARD_DEVIATION 8.64 • n=6 Participants	175.8 cm STANDARD_DEVIATION 9.41 • n=6 Participants	170.8 cm STANDARD_DEVIATION 8.16 • n=6 Participants	174.3 cm STANDARD_DEVIATION 9.89 • n=6 Participants	178.3 cm STANDARD_DEVIATION 5.35 • n=6 Participants	174.6 cm STANDARD_DEVIATION 8.25 • n=97 Participants
Body Weight	76.91 kg STANDARD_DEVIATION 13.376 • n=18 Participants	85.70 kg STANDARD_DEVIATION 19.447 • n=6 Participants	75.58 kg STANDARD_DEVIATION 10.193 • n=6 Participants	81.35 kg STANDARD_DEVIATION 11.542 • n=6 Participants	78.12 kg STANDARD_DEVIATION 14.972 • n=6 Participants	74.60 kg STANDARD_DEVIATION 14.594 • n=7 Participants	79.93 kg STANDARD_DEVIATION 10.994 • n=6 Participants	76.13 kg STANDARD_DEVIATION 13.650 • n=6 Participants	82.35 kg STANDARD_DEVIATION 15.599 • n=6 Participants	80.93 kg STANDARD_DEVIATION 14.020 • n=6 Participants	81.63 kg STANDARD_DEVIATION 19.397 • n=6 Participants	73.05 kg STANDARD_DEVIATION 14.729 • n=6 Participants	70.98 kg STANDARD_DEVIATION 15.157 • n=6 Participants	78.65 kg STANDARD_DEVIATION 13.827 • n=6 Participants	78.07 kg STANDARD_DEVIATION 13.925 • n=97 Participants
Body Mass Index	25.23 kg/m2 STANDARD_DEVIATION 3.626 • n=18 Participants	26.33 kg/m2 STANDARD_DEVIATION 3.912 • n=6 Participants	26.03 kg/m2 STANDARD_DEVIATION 4.479 • n=6 Participants	25.98 kg/m2 STANDARD_DEVIATION 3.378 • n=6 Participants	25.78 kg/m2 STANDARD_DEVIATION 2.662 • n=6 Participants	24.67 kg/m2 STANDARD_DEVIATION 3.119 • n=7 Participants	26.45 kg/m2 STANDARD_DEVIATION 2.402 • n=6 Participants	26.37 kg/m2 STANDARD_DEVIATION 2.382 • n=6 Participants	27.18 kg/m2 STANDARD_DEVIATION 5.115 • n=6 Participants	24.55 kg/m2 STANDARD_DEVIATION 3.462 • n=6 Participants	26.18 kg/m2 STANDARD_DEVIATION 4.659 • n=6 Participants	24.83 kg/m2 STANDARD_DEVIATION 3.435 • n=6 Participants	23.15 kg/m2 STANDARD_DEVIATION 2.673 • n=6 Participants	24.60 kg/m2 STANDARD_DEVIATION 3.200 • n=6 Participants	25.48 kg/m2 STANDARD_DEVIATION 3.451 • n=97 Participants

PRIMARY outcome

Timeframe: Through study completion, an average of 7 weeks

Population: The safety analysis set included all participants who received at least 1 dose of study drug.

A treatment-emergent adverse-event (TEAE) was defined as an adverse event that started during or after first dosing, or started prior to first dosing and increased in severity after first dosing.

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo n=18 Participants Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=6 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg n=6 Participants Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg n=6 Participants Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg n=7 Participants Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg n=6 Participants Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg n=6 Participants Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg n=6 Participants Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg n=6 Participants Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo n=6 Participants Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD n=6 Participants Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID n=6 Participants Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID n=6 Participants Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
Number of Participants With Treatment-Emergent Adverse Events	3 Participants	0 Participants	0 Participants	4 Participants	1 Participants	2 Participants	3 Participants	2 Participants	4 Participants	5 Participants	6 Participants	3 Participants	2 Participants	4 Participants

SECONDARY outcome

Timeframe: From pre-dose to up to 48 hours post-dose

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the AM1476 concentrations for one participant were below the level of quantification at all timepoints.

maximum plasma concentration

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo n=5 Participants Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=6 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg n=6 Participants Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg n=7 Participants Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg n=6 Participants Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg n=6 Participants Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg n=6 Participants Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg n=6 Participants Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
Cmax	0.165 ng/mL Geometric Coefficient of Variation 46.8	0.785 ng/mL Geometric Coefficient of Variation 43.4	3.83 ng/mL Geometric Coefficient of Variation 36.2	30.0 ng/mL Geometric Coefficient of Variation 57.6	119 ng/mL Geometric Coefficient of Variation 48.9	260 ng/mL Geometric Coefficient of Variation 102.2	334 ng/mL Geometric Coefficient of Variation 64.4	654 ng/mL Geometric Coefficient of Variation 89.7	1250 ng/mL Geometric Coefficient of Variation 35.8	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476

maximum plasma concentration

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo n=6 Participants Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=6 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
Cmax Day 1	18.8 ng/mL Geometric Coefficient of Variation 63.5	116 ng/mL Geometric Coefficient of Variation 52.1	252 ng/mL Geometric Coefficient of Variation 41.6	—	—	—	—	—	—	—	—	—	—	—
Cmax Day 10	26.0 ng/mL Geometric Coefficient of Variation 40.9	202 ng/mL Geometric Coefficient of Variation 48.4	278 ng/mL Geometric Coefficient of Variation 32.6	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From pre-dose to up to 48 hours post-dose

time to Cmax

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo n=5 Participants Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=6 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg n=6 Participants Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg n=7 Participants Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg n=6 Participants Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg n=6 Participants Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg n=6 Participants Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg n=6 Participants Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
Tmax	1.50 hour Interval 0.5 to 3.0	1.75 hour Interval 1.0 to 2.0	1.00 hour Interval 0.5 to 1.0	0.983 hour Interval 0.5 to 1.5	1.00 hour Interval 0.5 to 1.5	1.01 hour Interval 1.0 to 2.0	1.51 hour Interval 1.0 to 2.0	1.00 hour Interval 1.0 to 3.0	1.00 hour Interval 0.5 to 2.0	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476

time to Cmax

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo n=6 Participants Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=6 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
Tmax Day 1	0.500 hour Interval 0.5 to 1.0	1.00 hour Interval 0.5 to 2.0	1.00 hour Interval 0.517 to 1.5	—	—	—	—	—	—	—	—	—	—	—
Tmax Day 10	0.775 hour Interval 0.5 to 2.0	1.00 hour Interval 0.5 to 1.5	1.25 hour Interval 1.0 to 1.5	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From pre-dose to up to 48 hours post-dose

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the t½ was not calculable due to the limited quantifiable AM1476 concentrations available.

terminal half-life

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=5 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg n=6 Participants Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg n=6 Participants Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg n=6 Participants Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg n=5 Participants Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg n=6 Participants Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg n=6 Participants Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
T½	—	2.52 hour Geometric Coefficient of Variation 14.8	4.58 hour Geometric Coefficient of Variation 49.4	8.34 hour Geometric Coefficient of Variation 40.6	13.7 hour Geometric Coefficient of Variation 112.8	10.1 hour Geometric Coefficient of Variation 19.5	7.84 hour Geometric Coefficient of Variation 9.1	8.91 hour Geometric Coefficient of Variation 8.7	7.36 hour Geometric Coefficient of Variation 24.1	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. A reliable characterization of the terminal half-life could not be obtained according the calculation criteria in the Statistical analytical plan for 2 participants dosed with 100 mg QD and 1 participant dosed with 375 mg BID on Day 10.

terminal half-life

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo n=6 Participants Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=6 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
T½ Day 1	5.70 hour Geometric Coefficient of Variation 19.6	3.23 hour Geometric Coefficient of Variation 8.4	2.89 hour Geometric Coefficient of Variation 12.2	—	—	—	—	—	—	—	—	—	—	—
T½ Day 10	11.4 hour Geometric Coefficient of Variation 27.9	12.8 hour Geometric Coefficient of Variation 16.6	15.8 hour Geometric Coefficient of Variation 21.6	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From pre-dose to up to 48 hours post-dose

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the AUC was not reported for 4 participants due to less than 3 consecutive quantifiable concentrations (calculation criteria in the Statistical analytical plan).

area under the curve from time 0 to time of the last quantifiable concentration

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo n=2 Participants Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=6 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg n=6 Participants Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg n=7 Participants Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg n=6 Participants Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg n=6 Participants Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg n=6 Participants Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg n=6 Participants Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
AUC0-tlast	NA h*ng/mL Geometric Coefficient of Variation NA Not calculated as only results from 2 participants	2.77 h*ng/mL Geometric Coefficient of Variation 26.1	15.0 h*ng/mL Geometric Coefficient of Variation 26.1	113 h*ng/mL Geometric Coefficient of Variation 33.6	312 h*ng/mL Geometric Coefficient of Variation 44.8	882 h*ng/mL Geometric Coefficient of Variation 73.2	1280 h*ng/mL Geometric Coefficient of Variation 46.8	3000 h*ng/mL Geometric Coefficient of Variation 75.2	4900 h*ng/mL Geometric Coefficient of Variation 28.2	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476

area under the curve over a dosing interval (tau)

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo n=6 Participants Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=6 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
AUC0-tau Day 1	77.7 h*ng/mL Geometric Coefficient of Variation 36.8	324 h*ng/mL Geometric Coefficient of Variation 43.6	702 h*ng/mL Geometric Coefficient of Variation 22.7	—	—	—	—	—	—	—	—	—	—	—
AUC0-tau Day 10	110 h*ng/mL Geometric Coefficient of Variation 16.5	574 h*ng/mL Geometric Coefficient of Variation 30.6	953 h*ng/mL Geometric Coefficient of Variation 28.6	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From pre-dose to up to 48 hours post-dose

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the apparent total clearance was not calculable due to the limited quantifiable AM1476 concentrations available.

apparent total clearance

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=5 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg n=6 Participants Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg n=6 Participants Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg n=6 Participants Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg n=5 Participants Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg n=6 Participants Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg n=6 Participants Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
CL/F	—	1480 L/h Geometric Coefficient of Variation 23.7	1550 L/h Geometric Coefficient of Variation 27.4	1080 L/h Geometric Coefficient of Variation 31.9	1030 L/h Geometric Coefficient of Variation 30.2	724 L/h Geometric Coefficient of Variation 71.8	620 L/h Geometric Coefficient of Variation 16.9	495 L/h Geometric Coefficient of Variation 75.0	487 L/h Geometric Coefficient of Variation 28.0	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476

apparent total clearance

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo n=6 Participants Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=6 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
CL/F Day 1	1220 L/h Geometric Coefficient of Variation 35.0	1080 L/h Geometric Coefficient of Variation 45.6	673 L/h Geometric Coefficient of Variation 21.6	—	—	—	—	—	—	—	—	—	—	—
CL/F Day 10	906 L/h Geometric Coefficient of Variation 16.5	653 L/h Geometric Coefficient of Variation 30.6	525 L/h Geometric Coefficient of Variation 28.6	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From pre-dose to up to 48 hours post-dose

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the apparent volume of distribution during the terminal phase was not calculable due to the limited quantifiable AM1476 concentrations available.

apparent volume of distribution during the terminal phase

Outcome measures

Outcome measures
Measure	Part A, Groups 1 to 9: Placebo Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules	Part A, Group 1: AM1476 1 mg n=5 Participants Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 2: AM1476 5 mg n=6 Participants Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 3: AM1476 25 mg n=6 Participants Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 4: AM1476 125 mg n=6 Participants Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 5: AM1476 375 mg n=6 Participants Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 6: AM1476 650 mg n=5 Participants Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 7: AM1476 950 mg n=6 Participants Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 8: AM1476 1500 mg n=6 Participants Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part A, Group 9: AM1476 2400 mg Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules	Part B, Groups 1 to 3: Placebo Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules	Part B, Group 1: AM1476 100 mg QD Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules	Part B, Group 2: AM1476 375 mg BID Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules	Part B, Group 3: AM1476 500 mg BID Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules
Vz/F	—	5380 L Geometric Coefficient of Variation 35.6	10200 L Geometric Coefficient of Variation 30.8	13000 L Geometric Coefficient of Variation 60.7	20400 L Geometric Coefficient of Variation 163.0	10500 L Geometric Coefficient of Variation 92.7	7010 L Geometric Coefficient of Variation 13.0	6360 L Geometric Coefficient of Variation 75.5	5180 L Geometric Coefficient of Variation 43.2	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.

Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. A reliable characterization of the apparent volume of distribution during the terminal phase could not be obtained according the calculation criteria in the Statistical analytical plan for 2 participants dosed with 100 mg QD and 1 participant dosed with 375 mg BID on Day 10.

apparent volume of distribution during the terminal phase