Osteoarthritis Pain
Conditions
Brief summary
To evaluate the efficacy of ACP-044 compared with placebo in the treatment of pain associated with osteoarthritis of the knee
Interventions
DRUGACP-044 Dose A
Oral dose of ACP-044 Dose A
DRUGACP-044 Dose B
Oral dose of ACP-044 Dose B
DRUGPlacebo
Placebo
Sponsors
ACADIA Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects ≥18 and \<65 years of age at the time of Screening * Has a body mass index (BMI) ≤39 kg/m2 at Screening * Confirmed history of pain associated with OA in the index knee * Willing to maintain current activity and exercise levels throughout the study * Willing and able to comply with clinic visits and study-related procedures * Consent to allow all radiographs and medical/surgical/hospitalization records of care received elsewhere to be shared with the Investigator and third parties who will examine the images (i.e., central x-ray reader)
Exclusion criteria
* Pain anywhere else in the body which is greater than or equal to OA pain in the index knee, or likely to interfere with subject's assessment of pain throughout the study, as judged by the Investigator * History or presence on imaging of knee arthropathy (osteonecrosis, subchondral insufficiency fracture, rapidly progressive OA type 1 or type 2), recent fall, injury, or trauma affecting the index knee, ligament tear, neuropathic joint arthropathy, knee dislocation (patella dislocation is eligible), extensive subchondral cysts, Baker's cyst, evidence of bone fragmentation or collapse, or primary metastatic tumor with the exception of chondromas, or pathological fractures during the Screening Period * History or presence at Screening of non-OA inflammatory joint disease (e.g., rheumatoid arthritis, lupus erythematosus, psoriatic arthritis, pseudo-gout, gout, spondyloarthropathy, joint infections within the past 5 years, Paget's disease of the spine, pelvis, or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy) or any condition that would interfere with the rating of OA pain * Recent arthroscopic surgery within 1 month of Screening; or has any planned surgery or procedure during the study * Use of monoamine reuptake inhibitors, tricyclic antidepressants, anticonvulsants, and/or serotonin norepinephrine reuptake inhibitors within 4 weeks prior to Screening * Unwilling to discontinue current use of analgesic medication following Screening and to adhere to study requirements for rescue treatments (study-provided acetaminophen to be taken as needed with a maximum daily dose of 2500 mg), including, but not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, selective cyclooxygenase 2 inhibitors, acetaminophen, or combinations thereof, within 7 days or five half-lives of the drug prior to the Baseline Pain Assessment Period, whichever is longer * Use of immediate- or extended-release or controlled-release opioids (e.g., oxycontin), transdermal fentanyl, or methadone within 3 months prior to Screening * Use of opioids, for the treatment of pain other than OA of the knee, with a morphine equivalent dose of ≥30 mg per day for more than 2 days per week within 1 month prior to Screening * Use of systemic (i.e., oral) corticosteroids or intra-articular corticosteroids in any joint within 30 days prior to the screening visit (topical, intranasal, and inhaled corticosteroids are permitted) * Intra-articular injection of any approved (i.e., hyaluronic acid and corticosteroids) or unapproved treatments (e.g., platelet-rich plasma, capsaicin) into the index knee within 3 months of Screening * Physical/occupational/chiropractic therapy for the lower extremities or acupuncture for the lower extremities within 30 days of Screening, or the need for such therapy during the study * Has current evidence, or history within the previous 12 weeks prior to Screening, of a serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, endocrinologic, or other medical disorder, that in the judgment of the Investigator and/or Medical Monitor would jeopardize the safe participation of the subject in the study * 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 Additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | 4 weeks | The 0-10 NRS consists of a single 11-point numeric scale, with 0 indicating no pain at all and 10 reflecting the worst pain imaginable. Due to the business decision to discontinue clinical development of ACP-044, this study was prematurely terminated. Efficacy was not evaluated in this study by using (planned) inferential statistics. For the purpose of results posting, changes in NRS over time are displayed using descriptive statistics. |
Countries
United States
Participant flow
Pre-assignment details
During the screening period of up to 4 weeks, patients were assessed for eligibility. Prohibited medication was to be discontinued. Eligible patients had to complete a Baseline Pain Assessment Period of about 7 days before randomization (allowed time window +3 days) to be instructed in the use of an electronic diary and to record pain scores and rescue medication use. Compliance with data recording was assessed for continued eligibility. Upon completion of this period, patients were randomised.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Administration of ACP-044 matching placebo 4 times daily (morning, noon, evening, night) | 21 |
| ACP-044 400 mg QID Administration 4 times daily (morning, noon, evening, night) of 400 mg ACP-044 At each the morning and evening administration, patients received one placebo tablet and one tablet containing ACP-044 400 mg. At each the noon and night administration, patients received one tablet containing ACP-044 400 mg. | 20 |
| ACP-044 800 mg BID Administration 2 times daily (morning, noon, evening, night) of 800 mg ACP-044 At each the morning and evening administration, patients received 2 tablets containing ACP-044 400 mg. At each the noon and night administration, patients received one placebo tablet. | 20 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Not further specified | 3 | 2 | 1 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | ACP-044 800 mg BID | ACP-044 400 mg QID |
|---|---|---|---|---|
| Age, Continuous | 56.7 years STANDARD_DEVIATION 5.02 | 57.2 years STANDARD_DEVIATION 5.01 | 56.8 years STANDARD_DEVIATION 5.31 | 58.1 years STANDARD_DEVIATION 4.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 14 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 45 Participants | 14 Participants | 17 Participants |
| Region of Enrollment United States | 21 participants | 61 participants | 20 participants | 20 participants |
| Sex: Female, Male Female | 14 Participants | 41 Participants | 13 Participants | 14 Participants |
| Sex: Female, Male Male | 7 Participants | 20 Participants | 7 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 21 | 4 / 20 | 4 / 20 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores
The 0-10 NRS consists of a single 11-point numeric scale, with 0 indicating no pain at all and 10 reflecting the worst pain imaginable. Due to the business decision to discontinue clinical development of ACP-044, this study was prematurely terminated. Efficacy was not evaluated in this study by using (planned) inferential statistics. For the purpose of results posting, changes in NRS over time are displayed using descriptive statistics.
Time frame: 4 weeks
Population: All patients randomised and treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 3 | 2.9 score on a scale | Standard Deviation 0.88 |
| Placebo | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Baseline | 5.4 score on a scale | Standard Deviation 1.81 |
| Placebo | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 2 | 3.0 score on a scale | Standard Deviation 1.28 |
| Placebo | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 1 | 3.1 score on a scale | Standard Deviation 1.81 |
| ACP-044 400 mg QID | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 2 | 3.9 score on a scale | Standard Deviation 2.26 |
| ACP-044 400 mg QID | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Baseline | 6.1 score on a scale | Standard Deviation 1.12 |
| ACP-044 400 mg QID | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 1 | 4.4 score on a scale | Standard Deviation 2.24 |
| ACP-044 400 mg QID | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 3 | 3.8 score on a scale | Standard Deviation 2.36 |
| ACP-044 400 mg QID | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 4 | 4.0 score on a scale | Standard Deviation 1.41 |
| ACP-044 800 mg BID | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Baseline | 5.6 score on a scale | Standard Deviation 1.64 |
| ACP-044 800 mg BID | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 4 | 3.0 score on a scale | — |
| ACP-044 800 mg BID | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 3 | 4.2 score on a scale | Standard Deviation 2.33 |
| ACP-044 800 mg BID | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 1 | 4.6 score on a scale | Standard Deviation 1.63 |
| ACP-044 800 mg BID | Weekly Average of the Daily Average Numeric Rating Scale (NRS) Pain Intensity Scores | Week 2 | 4.2 score on a scale | Standard Deviation 2.19 |