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

Study Overview
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Brief Summary
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To evaluate the efficacy of ACP-044 compared with placebo in the treatment of acute postoperative pain

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ACP-044 for Acute Postoperative Pain Following Orthopedic Surgery (Bunionectomy)

Conditions
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Acute Postoperative Pain, Bunionectomy

Intervention / Treatment
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* Drug: ACP-044 Dose A
* Drug: ACP-044 Dose B
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 and <60 years of age at the time of Screening Has a body mass index (BMI) <40 kg/m2 Able to understand and provide signed informed consent Able to complete subject-reported outcome measures Is in need of a primary unilateral, first metatarsal bunionectomy with osteotomy and internal fixation under regional anesthesia and sedation Willing to remain inpatient at the study center for 4 days following surgery Exclusion Criteria: Has had a contralateral foot bunionectomy in the past 3 months Has a planned concurrent surgical procedure (e.g. bilateral bunionectomy or collateral procedures like hammertoe correction on the surgical foot) Any subacute or chronic pain condition or use of a medication that would impair/impact the ability to rate the pain associated with the bunionectomy, in the opinion of the Investigator and Medical Monitor Has known or suspected regular use of opioids within the previous 6 months Has taken opioids within 24 hours prior to the scheduled surgery or within five half-lives of the drug, whichever is longer Has a known or suspected history of drug abuse, a positive drug screen at Screening or Day -1, or a recent (i.e., within the last 5 years) history of alcohol abuse. Subjects using marijuana are not allowed to participate in the study. Has taken any aspirin (ASA) or non-steroidal anti-inflammatory drugs (NSAIDs) within 2 days prior to the scheduled surgery or within five half-lives of the drug, whichever is longer Has initiated treatment with any medications within 1 month prior to study drug administration that could impact pain control or quantitation of their pain response Has been administered systemic steroids within five half-lives or 10 days prior to administration of study drug, whichever is longer Has current evidence, or medical history of a serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, endocrinologic, or other medical disorder, within the previous 12 weeks prior to Screening and on Day -1, that in the judgment of the Investigator and/or Medical Monitor would jeopardize the safe participation of the subject in the study. Also, subject must not have had a malignancy in the last year, with the exception of nonmetastatic basal cell of the skin or localized carcinoma in situ of the cervix. Is judged by the Investigator or the Medical Monitor to be inappropriate for the study Additional inclusion/exclusion criteria apply. Patients will be evaluated at screening to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically, if it is determined that their baseline health and psychiatric condition do not meet all pre-specified entry criteria).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug - ACP-044 Dose A<br>ACP-044 Dose A | Drug: ACP-044 Dose A<br>* Oral dose of ACP-044 Dose A<br>|
| Experimental: Drug - ACP-044 Dose B<br>ACP-044 Dose B | Drug: ACP-044 Dose B<br>* Oral dose of ACP-044 Dose B<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Oral dose of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 0-24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Rescue Medication Use After Time 0 (When First Dose on Day 1 is Administered) |  | 0-72 hours | 
| Proportion of Subjects Who Were Opioid Free Through 24 Hours |  | 0-24 hours | 
| Proportion of Subjects Who Were Opioid Free Through 48 Hours |  | 0-48 hours | 
| Proportion of Subjects Who Were Opioid Free Through 72 Hours |  | 0-72 hours | 
| Mean AUC of the NRS of Pain Intensity Scores From Time 0 Through 48 Hours for ACP-044 | 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. | 0-48 hours | 
| Mean AUC of the NRS of Pain Intensity Scores From Time 0 Through 72 Hours for ACP-044 | 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. | 0-72 hours | 
| Mean AUC of the NRS of Pain Intensity Scores From Time 0 Through 4 Hours for ACP-044 | 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. | 0-4 hours | 
| Mean AUC of the NRS of Pain Intensity Scores From Time 0 Through 6 Hours for ACP-044 | 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. | 0-6 hours | 
| Mean AUC of the NRS of Pain Intensity Scores From Time 0 Through 12 Hours for ACP-044 | 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. | 0-12 hours | 
| Mean AUC of the NRS of Pain Intensity Scores From 24 Through 48 Hours for ACP-044 | 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. | 24-48 hours | 
| Mean AUC of the NRS of Pain Intensity Scores From Time 48 Through 72 Hours for ACP-044 | 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. | 48-72 hours | 
| Rescue Medication Taken During 0-24 Hours | Number of instances of rescue medication taken during first 24 hours. | 0-24 hours | 
| Rescue Medication Taken During 24-48 Hours | Number of instances of rescue medication taken during 24-48 hours. | 24-48 hours | 
| Rescue Medication Taken During 48-72 Hours | Number of instances of rescue medication taken during 48-72 hours. | 48-72 hours | 
| Rescue Medication Taken During 0-48 Hours | Number of instances of rescue medication taken during first 48 hours. | 0-48 hours | 
| Rescue Medication Taken During 0-72 Hours | Number of instances of rescue medication taken during first 72 hours. | 0-72 hours | 
| Proportion of Subjects Who Did Not Use Rescue Medication Through 24 Hours |  | 0-24 hours | 
| Proportion of Subjects Who Did Not Use Rescue Medication Through 48 Hours |  | 0-48 hours | 
| Proportion of Subjects Who Did Not Use Rescue Medication Through 72 Hours |  | 0-72 Hours | 
| Proportion of Subjects Who Are Pain Free (NRS ≤2) at 24 Hours |  | 0-24 hours | 
| Proportion of Subjects Who Are Pain Free (NRS ≤2) at 48 Hours |  | 0-48 hours | 
| Proportion of Subjects Who Are Pain Free (NRS ≤2) at 72 Hours |  | 0-72 hours | 
| Number of Hours Subjects Are Pain Free (NRS ≤2) |  | 0-72 hours | 
| Proportion of Subjects Who Were Opioid Free During 24-48 Hours |  | 24-48 hours | 
| Proportion of Subjects Who Were Opioid Free During 48-72 Hours |  | 48-72 hours | 
| Global Evaluation of Study Drug Just Before Time of First Rescue Medication Relative to Time 0 (When First Dose on Day 1 is Administered) | 5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent | First rescue medication dose, up to 24 hours post first dose. | 
| Global Evaluation of Study Drug at the End of 24 Hours Relative to Time 0 (When First Dose on Day 1 is Administered) | 5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent | 24 hours | 
| Global Evaluation of Study Drug at the End of 48 Hours Relative to Time 0 (When First Dose on Day 1 is Administered) | 5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent | 48 hours | 
| Global Evaluation of Study Drug at the End of 72 Hours Relative to Time 0 (When First Dose on Day 1 is Administered) | 5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent | 72 hours |