Acute Pain
Conditions
Brief summary
This study will evaluate the safety, efficacy, and PK of low dose (750 mg) and high-dose (1250 mg) XG005 oral tablets compared with placebo in subjects undergoing bunionectomy. Subjects will be confined in the clinic from check-in through 72 hours post-surgery to monitor subject safety.
Detailed description
This is a multi-center, randomized, double-blind, parallel-group, placebo-controlled study. Eligible subjects will be randomized in a 1:1:1 ratio to receive either 750 mg XG005, 1250 mg XG005, or placebo, twice a day, post bunionectomy surgery in domiciled clinic. Subjects and all study staff performing study assessments will be blinded to treatment allocation. Subjects will be discharged at a reasonable hour of the day after the end of the 72-hour treatment period.There will be a Follow-up Visit on Day 15.
Interventions
DRUGXG005 tablet
Subjects will receive XG005 prior to surgery and every 12 hours for 72 hours.
DRUGPlacebo tablet
Subjects will receive placebo prior to surgery and every 12 hours for 72 hours.
Sponsors
Xgene Pharmaceutical Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Main inclusion criteria: * Scheduled to undergo unilateral first metatarsal bunionectomy * Have negative urine drug screen * Non-pregnant, non-lactating Main
Exclusion criteria
* Medical condition or history that in the investigator's opinion could adversely impact the subject's participation or safety * Use of disallowed medications (e.g. pain medication, CNS active drugs such as benzodiazepines, tricyclic antidepressants, Serotonin, and norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), or any other serotonergic medications, parenteral or oral corticosteroids) * Antihypertensive agent or diabetic regimen at a dose that has not been stable for at least 30 days * Digoxin, warfarin lithium, theophylline preparations, aminoglycosides, and all antiarrhythmics * Monoamine oxidase inhibitors (MAOIs) * Positive HbsAg and/or anti-HBc but negative anti-HBs * HIV infection * History of illicit drug use * History of opioid dependence * History of NSAID-induced bronchospasm or presence of nasal polyps, history of asthma or chronic rhinitis * Significant history of allergic reactions or known intolerance to naproxen, pregabalin or any gabapentinoid, or to any rescue medication used in the study, or any medication used in the surgical and anesthetic protocol. * Presence of severe depression as indicated by Patient Health Questionnaire (PHQ 9) total score of ≥20 or item 9 score \>0 * Presence of severe anxiety as indicated by General Anxiety Disorder (GAD-7) score of ≥15 * Presence of history of suicidal behavior or ideation as indicated by the C-SSRS
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compared the Summed Pain Intensity From the End of Surgery to 48 Hours (SPI48) Between the High-dose XG005 Group and the Placebo Group Postoperatively. | SPI NPRS collection times occurred at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours, within a ±10-minute window. | The primary efficacy endpoint compared the Summed Pain Intensity from the End of Surgery to 48 Hours (SPI48) between the high-dose XG005 group and the placebo group postoperatively. Subject-reported pain assessments via a standard 11-point Numeric Pain Rating Scale (NPRS, a scale of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10). 0 means no pain,10 means worst pain imaginable) at the following time points post-end of surgery: 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours within a ±10-minute window. Each pairwise treatment comparison (e.g., high dose vs. placebo, low dose vs. placebo) was analyzed using a separate ANCOVA model that included only the relevant treatment arms and adjusted for study site. As a result, the placebo least squares mean may differ slightly across comparisons due to differences in covariate adjustment. For the high-dose versus placebo comparison, SPI48 ranged from 0 to 425 in the high-dose group and from 0 to 446 in the placebo group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compared the Summed Pain Intensity From the End of Surgery to 48 Hours (SPI48) Between the Low-dose XG005 Group and the Placebo Group Postoperatively. | SPI NPRS collection times occurred at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours, within a ±10-minute window. | The secondary efficacy endpoint compared the Summed Pain Intensity from the End of Surgery to 48 Hours (SPI48) between the low-dose XG005 group and the placebo group postoperatively. Subject-reported pain assessments via a standard 11-point Numeric Pain Rating Scale (NPRS, a scale of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10). 0 means no pain,10 means worst pain imaginable) at the following time points post-end of surgery: 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours within a ±10-minute window. The pairwise treatment comparison was analyzed using a separate ANCOVA model that included only the relevant treatment arms and adjusted for study site. As a result, the placebo least squares mean may differ slightly across comparisons due to differences in covariate adjustment. For the low-dose versus placebo comparison, SPI48 ranged from 0 to 383 in the low-dose group and from 0 to 446 in the placebo group. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Dose XG005 1250 mg Q12 hours | 152 |
| Low Dose XG005 750 mg Q12 hours | 149 |
| Placebo Placebo Q12 hours | 149 |
| Total | 450 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 |
| Overall Study | COVID Positive | 0 | 1 | 0 |
| Overall Study | Did Not Disclose Amount of EtOH Consumed | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 7 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Non-Compliance | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 4 | 3 |
Baseline characteristics
| Characteristic | High Dose | Low Dose | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Age, Categorical >=65 years | 5 Participants | 8 Participants | 11 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 146 Participants | 140 Participants | 137 Participants | 423 Participants |
| Body Mass Index | 28.37 kg/m^2 STANDARD_DEVIATION 4.37 | 28.52 kg/m^2 STANDARD_DEVIATION 4.464 | 28.05 kg/m^2 STANDARD_DEVIATION 4.764 | 28.32 kg/m^2 STANDARD_DEVIATION 4.527 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 57 Participants | 50 Participants | 57 Participants | 164 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 97 Participants | 91 Participants | 283 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 40 Participants | 55 Participants | 49 Participants | 144 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 7 Participants | 5 Participants | 14 Participants |
| Race (NIH/OMB) White | 103 Participants | 82 Participants | 94 Participants | 279 Participants |
| Region of Enrollment United States | 152 Participants | 149 Participants | 149 Participants | 450 Participants |
| Sex: Female, Male Female | 123 Participants | 117 Participants | 120 Participants | 360 Participants |
| Sex: Female, Male Male | 29 Participants | 32 Participants | 29 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 152 | 0 / 149 | 0 / 147 |
| other Total, other adverse events | 88 / 152 | 69 / 149 | 62 / 147 |
| serious Total, serious adverse events | 0 / 152 | 0 / 149 | 0 / 147 |
Outcome results
Primary
Compared the Summed Pain Intensity From the End of Surgery to 48 Hours (SPI48) Between the High-dose XG005 Group and the Placebo Group Postoperatively.
The primary efficacy endpoint compared the Summed Pain Intensity from the End of Surgery to 48 Hours (SPI48) between the high-dose XG005 group and the placebo group postoperatively. Subject-reported pain assessments via a standard 11-point Numeric Pain Rating Scale (NPRS, a scale of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10). 0 means no pain,10 means worst pain imaginable) at the following time points post-end of surgery: 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours within a ±10-minute window. Each pairwise treatment comparison (e.g., high dose vs. placebo, low dose vs. placebo) was analyzed using a separate ANCOVA model that included only the relevant treatment arms and adjusted for study site. As a result, the placebo least squares mean may differ slightly across comparisons due to differences in covariate adjustment. For the high-dose versus placebo comparison, SPI48 ranged from 0 to 425 in the high-dose group and from 0 to 446 in the placebo group.
Time frame: SPI NPRS collection times occurred at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours, within a ±10-minute window.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| High dose | Compared the Summed Pain Intensity From the End of Surgery to 48 Hours (SPI48) Between the High-dose XG005 Group and the Placebo Group Postoperatively. | 132.63 Numeric score | Standard Error 8.004 |
| Placebo | Compared the Summed Pain Intensity From the End of Surgery to 48 Hours (SPI48) Between the High-dose XG005 Group and the Placebo Group Postoperatively. | 285.99 Numeric score | Standard Error 8.183 |
p-value: <0.000195% CI: [-173.8, -132.91]ANCOVA
Secondary
Compared the Summed Pain Intensity From the End of Surgery to 48 Hours (SPI48) Between the Low-dose XG005 Group and the Placebo Group Postoperatively.
The secondary efficacy endpoint compared the Summed Pain Intensity from the End of Surgery to 48 Hours (SPI48) between the low-dose XG005 group and the placebo group postoperatively. Subject-reported pain assessments via a standard 11-point Numeric Pain Rating Scale (NPRS, a scale of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10). 0 means no pain,10 means worst pain imaginable) at the following time points post-end of surgery: 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours within a ±10-minute window. The pairwise treatment comparison was analyzed using a separate ANCOVA model that included only the relevant treatment arms and adjusted for study site. As a result, the placebo least squares mean may differ slightly across comparisons due to differences in covariate adjustment. For the low-dose versus placebo comparison, SPI48 ranged from 0 to 383 in the low-dose group and from 0 to 446 in the placebo group.
Time frame: SPI NPRS collection times occurred at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours, within a ±10-minute window.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| High dose | Compared the Summed Pain Intensity From the End of Surgery to 48 Hours (SPI48) Between the Low-dose XG005 Group and the Placebo Group Postoperatively. | 157.86 Numeric score | Standard Error 8.345 |
| Placebo | Compared the Summed Pain Intensity From the End of Surgery to 48 Hours (SPI48) Between the Low-dose XG005 Group and the Placebo Group Postoperatively. | 289.50 Numeric score | Standard Error 8.5 |
p-value: <0.000195% CI: [-153.13, -110.16]ANCOVA