Trial Outcomes & Findings for Evaluate the Efficacy and Safety of ACP-044 for the Treatment of Acute Postoperative Pain Following Bunionectomy (NCT NCT04855240)

NCT ID: NCT04855240

Last Updated: 2023-05-03

Results Overview

Pain (efficacy) assessments were recorded hourly (±15 minutes) for a 12-hour interval on Day 1 beginning immediately prior to the fifth dose (time 0) administered in the study. Pain assessments were continued every 3 hours during the subsequent 12 hour interval, and then every 6 hours thereafter until 72 hours, then once daily in the morning until the follow-up clinical visit. Pain assessments were also obtained immediately prior to the administration of rescue medication. A 0 to 10 Numeric Rating Scale of Pain Intensity (NRS) was used to assess the subject's pain. Subjects were asked: "Please describe your foot pain at the present time from 0 to 10 where "0" means "no pain at all" and "10" means "the worst pain imaginable." The area under the curve is generated using the following timepoints beginning immediately prior to the fifth dose (time 0): 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, and 24 hours.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 239 participants
• Primary outcome timeframe: 0-24 hours
• Results posted on: 2023-05-03

Participant Flow

Participant milestones

Measure	Drug - ACP-044 400 mg Q6H ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo Placebo Placebo: Oral dose of placebo
Overall Study STARTED	81	78	80
Overall Study COMPLETED	77	73	75
Overall Study NOT COMPLETED	4	5	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluate the Efficacy and Safety of ACP-044 for the Treatment of Acute Postoperative Pain Following Bunionectomy

Baseline characteristics by cohort

Measure	Drug - ACP-044 400 mg Q6H n=81 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo	Total n=239 Participants Total of all reporting groups
Age, Continuous	42.9 years STANDARD_DEVIATION 12.38 • n=5 Participants	46.9 years STANDARD_DEVIATION 10.93 • n=7 Participants	42.7 years STANDARD_DEVIATION 11.46 • n=5 Participants	44.1 years STANDARD_DEVIATION 11.73 • n=4 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	65 Participants n=7 Participants	63 Participants n=5 Participants	196 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants	43 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants n=5 Participants	26 Participants n=7 Participants	22 Participants n=5 Participants	70 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	58 Participants n=5 Participants	52 Participants n=7 Participants	58 Participants n=5 Participants	168 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Primary Race · White	62 Participants n=5 Participants	58 Participants n=7 Participants	58 Participants n=5 Participants	178 Participants n=4 Participants
Race/Ethnicity, Customized Primary Race · Black or African American	16 Participants n=5 Participants	14 Participants n=7 Participants	17 Participants n=5 Participants	47 Participants n=4 Participants
Race/Ethnicity, Customized Primary Race · Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Primary Race · American Indian or Alaska Native	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Primary Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Primary Race · Other	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	81 participants n=5 Participants	78 participants n=7 Participants	80 participants n=5 Participants	239 participants n=4 Participants

PRIMARY outcome

Timeframe: 0-24 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Pain (efficacy) assessments were recorded hourly (±15 minutes) for a 12-hour interval on Day 1 beginning immediately prior to the fifth dose (time 0) administered in the study. Pain assessments were continued every 3 hours during the subsequent 12 hour interval, and then every 6 hours thereafter until 72 hours, then once daily in the morning until the follow-up clinical visit. Pain assessments were also obtained immediately prior to the administration of rescue medication.

A 0 to 10 Numeric Rating Scale of Pain Intensity (NRS) was used to assess the subject's pain.

Subjects were asked: "Please describe your foot pain at the present time from 0 to 10 where "0" means "no pain at all" and "10" means "the worst pain imaginable." The area under the curve is generated using the following timepoints beginning immediately prior to the fifth dose (time 0): 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, and 24 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) of Pain Intensity Scores From Time 0 (When First Dose on Day 1 is Administered) Through 24 Hours	116.9 Score on scale * hour Standard Error 5.55	129.0 Score on scale * hour Standard Error 5.58	127.4 Score on scale * hour Standard Error 5.52

SECONDARY outcome

Timeframe: 0-72 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Time to First Rescue Medication Use After Time 0 (When First Dose on Day 1 is Administered)	6.0 hours Standard Error 0.5	5.7 hours Standard Error 0.7	7.0 hours Standard Error 0.7

SECONDARY outcome

Timeframe: 0-24 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Were Opioid Free Through 24 Hours	48 Participants	34 Participants	40 Participants

SECONDARY outcome

Timeframe: 0-48 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Were Opioid Free Through 48 Hours	45 Participants	32 Participants	40 Participants

SECONDARY outcome

Timeframe: 0-72 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Were Opioid Free Through 72 Hours	44 Participants	31 Participants	39 Participants

SECONDARY outcome

Timeframe: 0-48 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Pain (efficacy) assessments were recorded hourly (±15 minutes) for a 12-hour interval on Day 1 beginning immediately prior to the fifth dose (time 0) administered in the study. Pain assessments were continued every 3 hours during the subsequent 12 hour interval, and then every 6 hours thereafter until 72 hours, then once daily in the morning until the follow-up clinical visit. Pain assessments were also obtained immediately prior to the administration of rescue medication.

A 0 to 10 Numeric Rating Scale of Pain Intensity (NRS) was used to assess the subject's pain.

Subjects were asked: "Please describe your foot pain at the present time from 0 to 10 where "0" means "no pain at all" and "10" means "the worst pain imaginable." The area under the curve is generated using the following timepoints beginning immediately prior to the fifth dose (time 0): 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 30, 36, 42, and 48 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Mean AUC of the NRS of Pain Intensity Scores From Time 0 Through 48 Hours for ACP-044	206.8 Score on scale * hour Standard Error 11.21	229.7 Score on scale * hour Standard Error 11.27	224.5 Score on scale * hour Standard Error 11.12

SECONDARY outcome

Timeframe: 0-72 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Pain (efficacy) assessments were recorded hourly (±15 minutes) for a 12-hour interval on Day 1 beginning immediately prior to the fifth dose (time 0) administered in the study. Pain assessments were continued every 3 hours during the subsequent 12 hour interval, and then every 6 hours thereafter until 72 hours, then once daily in the morning until the follow-up clinical visit. Pain assessments were also obtained immediately prior to the administration of rescue medication.

A 0 to 10 Numeric Rating Scale of Pain Intensity (NRS) was used to assess the subject's pain.

Subjects were asked: "Please describe your foot pain at the present time from 0 to 10 where "0" means "no pain at all" and "10" means "the worst pain imaginable." The area under the curve is generated using the following timepoints beginning immediately prior to the fifth dose (time 0): 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, and 72 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Mean AUC of the NRS of Pain Intensity Scores From Time 0 Through 72 Hours for ACP-044	274.3 Score on scale * hour Standard Error 16.72	304.7 Score on scale * hour Standard Error 16.81	296.9 Score on scale * hour Standard Error 16.59

SECONDARY outcome

Timeframe: 0-4 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Pain (efficacy) assessments were recorded hourly (±15 minutes) for a 12-hour interval on Day 1 beginning immediately prior to the fifth dose (time 0) administered in the study. Pain assessments were continued every 3 hours during the subsequent 12 hour interval, and then every 6 hours thereafter until 72 hours, then once daily in the morning until the follow-up clinical visit. Pain assessments were also obtained immediately prior to the administration of rescue medication.

A 0 to 10 Numeric Rating Scale of Pain Intensity (NRS) was used to assess the subject's pain.

Subjects were asked: "Please describe your foot pain at the present time from 0 to 10 where "0" means "no pain at all" and "10" means "the worst pain imaginable." The area under the curve is generated using the following timepoints beginning immediately prior to the fifth dose (time 0): 0, 1, 2, 3, and 4 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Mean AUC of the NRS of Pain Intensity Scores From Time 0 Through 4 Hours for ACP-044	18.3 Score on scale * hour Standard Error 1.25	20.5 Score on scale * hour Standard Error 1.26	18.6 Score on scale * hour Standard Error 1.24

SECONDARY outcome

Timeframe: 0-6 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Pain (efficacy) assessments were recorded hourly (±15 minutes) for a 12-hour interval on Day 1 beginning immediately prior to the fifth dose (time 0) administered in the study. Pain assessments were continued every 3 hours during the subsequent 12 hour interval, and then every 6 hours thereafter until 72 hours, then once daily in the morning until the follow-up clinical visit. Pain assessments were also obtained immediately prior to the administration of rescue medication.

A 0 to 10 Numeric Rating Scale of Pain Intensity (NRS) was used to assess the subject's pain.

Subjects were asked: "Please describe your foot pain at the present time from 0 to 10 where "0" means "no pain at all" and "10" means "the worst pain imaginable." The area under the curve is generated using the following timepoints beginning immediately prior to the fifth dose (time 0): 0, 1, 2, 3, 4, 5, and 6 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Mean AUC of the NRS of Pain Intensity Scores From Time 0 Through 6 Hours for ACP-044	28.6 Score on scale * hour Standard Error 1.86	32.4 Score on scale * hour Standard Error 1.86	29.8 Score on scale * hour Standard Error 1.84

SECONDARY outcome

Timeframe: 0-12 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Pain (efficacy) assessments were recorded hourly (±15 minutes) for a 12-hour interval on Day 1 beginning immediately prior to the fifth dose (time 0) administered in the study. Pain assessments were continued every 3 hours during the subsequent 12 hour interval, and then every 6 hours thereafter until 72 hours, then once daily in the morning until the follow-up clinical visit. Pain assessments were also obtained immediately prior to the administration of rescue medication.

A 0 to 10 Numeric Rating Scale of Pain Intensity (NRS) was used to assess the subject's pain.

Subjects were asked: "Please describe your foot pain at the present time from 0 to 10 where "0" means "no pain at all" and "10" means "the worst pain imaginable." The area under the curve is generated using the following timepoints beginning immediately prior to the fifth dose (time 0): 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Mean AUC of the NRS of Pain Intensity Scores From Time 0 Through 12 Hours for ACP-044	61.7 Score on scale * hour Standard Error 3.18	66.6 Score on scale * hour Standard Error 3.19	65.9 Score on scale * hour Standard Error 3.15

SECONDARY outcome

Timeframe: 24-48 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Pain (efficacy) assessments were recorded hourly (±15 minutes) for a 12-hour interval on Day 1 beginning immediately prior to the fifth dose (time 0) administered in the study. Pain assessments were continued every 3 hours during the subsequent 12 hour interval, and then every 6 hours thereafter until 72 hours, then once daily in the morning until the follow-up clinical visit. Pain assessments were also obtained immediately prior to the administration of rescue medication.

A 0 to 10 Numeric Rating Scale of Pain Intensity (NRS) was used to assess the subject's pain.

Subjects were asked: "Please describe your foot pain at the present time from 0 to 10 where "0" means "no pain at all" and "10" means "the worst pain imaginable." The area under the curve is generated using the following timepoints beginning immediately prior to the fifth dose (time 0): 24, 30, 36, 42, and 48 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Mean AUC of the NRS of Pain Intensity Scores From 24 Through 48 Hours for ACP-044	90.2 score on a scale * hour Standard Error 6.29	100.8 score on a scale * hour Standard Error 6.32	97.3 score on a scale * hour Standard Error 6.24

SECONDARY outcome

Timeframe: 48-72 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Pain (efficacy) assessments were recorded hourly (±15 minutes) for a 12-hour interval on Day 1 beginning immediately prior to the fifth dose (time 0) administered in the study. Pain assessments were continued every 3 hours during the subsequent 12 hour interval, and then every 6 hours thereafter until 72 hours, then once daily in the morning until the follow-up clinical visit. Pain assessments were also obtained immediately prior to the administration of rescue medication.

A 0 to 10 Numeric Rating Scale of Pain Intensity (NRS) was used to assess the subject's pain.

Subjects were asked: "Please describe your foot pain at the present time from 0 to 10 where "0" means "no pain at all" and "10" means "the worst pain imaginable." The area under the curve is generated using the following timepoints beginning immediately prior to the fifth dose (time 0): 48, 54, 60, 66, and 72 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Mean AUC of the NRS of Pain Intensity Scores From Time 48 Through 72 Hours for ACP-044	67.9 score on a scale * hour Standard Error 6.27	75.4 score on a scale * hour Standard Error 6.32	73.0 score on a scale * hour Standard Error 6.22

SECONDARY outcome

Timeframe: 0-24 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Number of instances of rescue medication taken during first 24 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Rescue Medication Taken During 0-24 Hours	2.1 instances Standard Error 0.21	2.6 instances Standard Error 0.21	2.3 instances Standard Error 0.21

SECONDARY outcome

Timeframe: 24-48 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Number of instances of rescue medication taken during 24-48 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Rescue Medication Taken During 24-48 Hours	1.0 instances Standard Error 0.17	1.2 instances Standard Error 0.17	1.1 instances Standard Error 0.17

SECONDARY outcome

Timeframe: 48-72 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Number of instances of rescue medication taken during 48-72 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Rescue Medication Taken During 48-72 Hours	0.5 instances Standard Error 0.12	0.7 instances Standard Error 0.12	0.6 instances Standard Error 0.12

SECONDARY outcome

Timeframe: 0-48 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Number of instances of rescue medication taken during first 48 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Rescue Medication Taken During 0-48 Hours	3.1 instances Standard Error 0.35	3.7 instances Standard Error 0.35	3.3 instances Standard Error 0.35

SECONDARY outcome

Timeframe: 0-72 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Number of instances of rescue medication taken during first 72 hours.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Rescue Medication Taken During 0-72 Hours	3.6 instances Standard Error 0.43	4.4 instances Standard Error 0.43	4.0 instances Standard Error 0.43

SECONDARY outcome

Timeframe: 0-24 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=77 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=79 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Did Not Use Rescue Medication Through 24 Hours	16 Participants	10 Participants	10 Participants

SECONDARY outcome

Timeframe: 0-48 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=77 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=79 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Did Not Use Rescue Medication Through 48 Hours	16 Participants	9 Participants	9 Participants

SECONDARY outcome

Timeframe: 0-72 Hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=78 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=77 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=79 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Did Not Use Rescue Medication Through 72 Hours	16 Participants	9 Participants	9 Participants

SECONDARY outcome

Timeframe: 0-24 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=78 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=76 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=75 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Are Pain Free (NRS ≤2) at 24 Hours	30 Participants	19 Participants	22 Participants

SECONDARY outcome

Timeframe: 0-48 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=77 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=73 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=75 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Are Pain Free (NRS ≤2) at 48 Hours	42 Participants	37 Participants	41 Participants

SECONDARY outcome

Timeframe: 0-72 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=77 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=72 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=76 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Are Pain Free (NRS ≤2) at 72 Hours	50 Participants	49 Participants	55 Participants

SECONDARY outcome

Timeframe: 0-72 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Number of Hours Subjects Are Pain Free (NRS ≤2)	29.0 hours Standard Error 2.48	22.8 hours Standard Error 2.49	23.0 hours Standard Error 2.46

SECONDARY outcome

Timeframe: 24-48 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Were Opioid Free During 24-48 Hours	65 Participants	59 Participants	59 Participants

SECONDARY outcome

Timeframe: 48-72 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=79 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 Participants Placebo Placebo: Oral dose of placebo
Proportion of Subjects Who Were Opioid Free During 48-72 Hours	72 Participants	65 Participants	70 Participants

SECONDARY outcome

Timeframe: First rescue medication dose, up to 24 hours post first dose.

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=59 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=61 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=61 Participants Placebo Placebo: Oral dose of placebo
Global Evaluation of Study Drug Just Before Time of First Rescue Medication Relative to Time 0 (When First Dose on Day 1 is Administered)	1.2 score on a scale Standard Error 0.16	1.5 score on a scale Standard Error 0.15	1.2 score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: 24 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=67 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=62 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=66 Participants Placebo Placebo: Oral dose of placebo
Global Evaluation of Study Drug at the End of 24 Hours Relative to Time 0 (When First Dose on Day 1 is Administered)	1.7 score on a scale Standard Error 0.16	2.0 score on a scale Standard Error 0.16	1.7 score on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: 48 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=75 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=75 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=74 Participants Placebo Placebo: Oral dose of placebo
Global Evaluation of Study Drug at the End of 48 Hours Relative to Time 0 (When First Dose on Day 1 is Administered)	2.2 score on a scale Standard Error 0.15	2.2 score on a scale Standard Error 0.15	2.0 score on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: 72 hours

Population: Two subjects in the ACP-044 Q6H group were included in the safety analysis set but not the full analysis set.

5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent

Outcome measures

Measure	Drug - ACP-044 400 mg Q6H n=76 Participants ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=75 Participants ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=76 Participants Placebo Placebo: Oral dose of placebo
Global Evaluation of Study Drug at the End of 72 Hours Relative to Time 0 (When First Dose on Day 1 is Administered)	2.3 score on a scale Standard Error 0.16	2.4 score on a scale Standard Error 0.16	2.1 score on a scale Standard Error 0.16

Adverse Events

Drug - ACP-044 400 mg Q6H

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Drug - ACP-044 1600 mg QD

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	Drug - ACP-044 400 mg Q6H n=81 participants at risk ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 participants at risk ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 participants at risk Placebo Placebo: Oral dose of placebo
Infections and infestations COVID-19 pneumonia	1.2% 1/81 • 62 days	0.00% 0/78 • 62 days	0.00% 0/80 • 62 days
Gastrointestinal disorders acute pancreatitis	0.00% 0/81 • 62 days	1.3% 1/78 • 62 days	0.00% 0/80 • 62 days

Other adverse events

Measure	Drug - ACP-044 400 mg Q6H n=81 participants at risk ACP-044 Dose A ACP-044 Dose A: Oral dose of ACP-044 400 mg Q6H	Drug - ACP-044 1600 mg QD n=78 participants at risk ACP-044 Dose B ACP-044 Dose B: Oral dose of ACP-044 1600 mg QD	Placebo n=80 participants at risk Placebo Placebo: Oral dose of placebo
Gastrointestinal disorders Nausea	18.5% 15/81 • 62 days	12.8% 10/78 • 62 days	13.8% 11/80 • 62 days
Gastrointestinal disorders Vomiting	6.2% 5/81 • 62 days	9.0% 7/78 • 62 days	3.8% 3/80 • 62 days
Gastrointestinal disorders Constipation	2.5% 2/81 • 62 days	3.8% 3/78 • 62 days	6.2% 5/80 • 62 days
Nervous system disorders Headache	12.3% 10/81 • 62 days	16.7% 13/78 • 62 days	16.2% 13/80 • 62 days
Nervous system disorders Dizziness	8.6% 7/81 • 62 days	3.8% 3/78 • 62 days	5.0% 4/80 • 62 days

Additional Information

Study Director

Acadia Pharmaceuticals Inc.

Phone: 844-422-2342

Email: medicalinformation@acadia-pharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place