Acute Pain, Pain, Postoperative
Conditions
Brief summary
The purpose of this phase 3 study is to evaluate the efficacy and safety of VVZ-149 Injections for the treatment of postoperative pain following laparoscopic colectomy.
Interventions
IV infusion of 1000 mg of VVZ-149
DRUGPlacebo
IV infusion of 0 mg of VVZ-149
Sponsors
Vivozon Pharmaceutical 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 No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women who are at least 18 years of age * Female subjects who are not pregnant or breastfeeding * Subjects undergoing a planned first laparoscopic colectomy * Subjects classified in American Society of Anesthesiologists (ASA) risk class of I or II * Subjects who report the pain intensity ≥ 5 on the NRS measured after surgery * Subjects who have the ability to understand study procedures and communicate clearly with the investigator and staff * Subjects who provide written informed consent prior to participation in the study Key
Exclusion criteria
* Subjects undergoing emergency or unplanned surgery * Subjects who had a previous laparoscopic colectomy procedure, or who had any laparoscopic resection procedure * Subjects with pre-existing conditions causing preoperative pain at the site of surgery * Female subjects who are pregnant or breastfeeding * Diagnosis of chronic pain (e.g., persistent pain with the intensity of NRS ≥ 5 at baseline)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Sum of Pain Intensity Differences for 12 Hours Post-dose (SPID 12) | 0-12 hours post-dose | Pain Intensity (PI) was assessed on an 11-point numerical rating scale from 0 (no pain) to 10 (worst pain imaginable). Time-weighted Sum of Pain Intensity Difference (PID) for 12 hours post-dose (SPID 12) was estimated using the linear trapezoidal rule (L x Hour) with the PI scores assigned from Time 0 to Time 12 hours post-dose using the following formula. The theoretical SPID 12 ranges from 0 to 120. A higher value of SPID indicates greater pain relief. SPID 12 = S \[T(i)-T(i-1)\] × \[PID(i)+PID(i-1)\]/2, when PID(i) =Predose PI-PI at Time i |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Patient-controlled Analgesia (PCA) Requests for 12 Hours Post-dose | 0-12 hours post-dose | Total number of patient-controlled analgesia (PCA) requests from Time 0 to Time 12 hours was compared between the VVZ-149 Injections group and the placebo group. |
| Total Amount of PCA and Rescue Medication Consumption for 12 Hours Post-dose | 0-12 hours post-dose | Total amount of PCA and rescue medication consumption from Time 0 to Time 12 hours was compared between the VVZ-149 Injections group and the placebo group. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VVZ-149 Injections IV infusion of 1000 mg of VVZ-149 | 141 |
| Placebo IV infusion of 0 mg of VVZ-149 | 143 |
| Total | 284 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Inclusion/exclusion criteria not met Inclusion/exclusion criteria not met | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 8 |
Baseline characteristics
| Characteristic | VVZ-149 Injections | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 50 Participants | 71 Participants | 121 Participants |
| Age, Categorical Between 18 and 65 years | 91 Participants | 72 Participants | 163 Participants |
| Age, Continuous | 60.8 years STANDARD_DEVIATION 9.66 | 62.8 years STANDARD_DEVIATION 9.76 | 61.8 years STANDARD_DEVIATION 9.75 |
| BMI | 24.66 kg/m2 STANDARD_DEVIATION 3.044 | 24.21 kg/m2 STANDARD_DEVIATION 2.61 | 24.44 kg/m2 STANDARD_DEVIATION 2.838 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 141 Participants | 143 Participants | 284 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment South Korea | 141 participants | 143 participants | 284 participants |
| Sex: Female, Male Female | 62 Participants | 59 Participants | 121 Participants |
| Sex: Female, Male Male | 79 Participants | 84 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 141 | 0 / 143 |
| other Total, other adverse events | 101 / 141 | 98 / 143 |
| serious Total, serious adverse events | 0 / 141 | 0 / 143 |
Outcome results
Primary
Time-weighted Sum of Pain Intensity Differences for 12 Hours Post-dose (SPID 12)
Pain Intensity (PI) was assessed on an 11-point numerical rating scale from 0 (no pain) to 10 (worst pain imaginable). Time-weighted Sum of Pain Intensity Difference (PID) for 12 hours post-dose (SPID 12) was estimated using the linear trapezoidal rule (L x Hour) with the PI scores assigned from Time 0 to Time 12 hours post-dose using the following formula. The theoretical SPID 12 ranges from 0 to 120. A higher value of SPID indicates greater pain relief. SPID 12 = S \[T(i)-T(i-1)\] × \[PID(i)+PID(i-1)\]/2, when PID(i) =Predose PI-PI at Time i
Time frame: 0-12 hours post-dose
Population: mITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VVZ-149 Injections | Time-weighted Sum of Pain Intensity Differences for 12 Hours Post-dose (SPID 12) | 26.83 score on a scale*hours | Standard Error 1.73 |
| Placebo | Time-weighted Sum of Pain Intensity Differences for 12 Hours Post-dose (SPID 12) | 19.89 score on a scale*hours | Standard Error 1.72 |
p-value: 0.004795% CI: [2.145, 11.731]ANOVA
Secondary
Total Amount of PCA and Rescue Medication Consumption for 12 Hours Post-dose
Total amount of PCA and rescue medication consumption from Time 0 to Time 12 hours was compared between the VVZ-149 Injections group and the placebo group.
Time frame: 0-12 hours post-dose
Population: mITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VVZ-149 Injections | Total Amount of PCA and Rescue Medication Consumption for 12 Hours Post-dose | Time 4-6 Hour | 24.0 mg | Standard Deviation 20.45 |
| VVZ-149 Injections | Total Amount of PCA and Rescue Medication Consumption for 12 Hours Post-dose | Time 2-4 Hour | 38.6 mg | Standard Deviation 28.28 |
| VVZ-149 Injections | Total Amount of PCA and Rescue Medication Consumption for 12 Hours Post-dose | Time 6-8 Hour | 19.1 mg | Standard Deviation 19.63 |
| VVZ-149 Injections | Total Amount of PCA and Rescue Medication Consumption for 12 Hours Post-dose | Time 8-10 Hour | 17.8 mg | Standard Deviation 19.64 |
| Placebo | Total Amount of PCA and Rescue Medication Consumption for 12 Hours Post-dose | Time 8-10 Hour | 24.9 mg | Standard Deviation 24.13 |
| Placebo | Total Amount of PCA and Rescue Medication Consumption for 12 Hours Post-dose | Time 2-4 Hour | 47.0 mg | Standard Deviation 32.92 |
| Placebo | Total Amount of PCA and Rescue Medication Consumption for 12 Hours Post-dose | Time 4-6 Hour | 31.9 mg | Standard Deviation 27 |
| Placebo | Total Amount of PCA and Rescue Medication Consumption for 12 Hours Post-dose | Time 6-8 Hour | 27.6 mg | Standard Deviation 25.36 |
Secondary
Total Number of Patient-controlled Analgesia (PCA) Requests for 12 Hours Post-dose
Total number of patient-controlled analgesia (PCA) requests from Time 0 to Time 12 hours was compared between the VVZ-149 Injections group and the placebo group.
Time frame: 0-12 hours post-dose
Population: mITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VVZ-149 Injections | Total Number of Patient-controlled Analgesia (PCA) Requests for 12 Hours Post-dose | Time 4-6 Hour | 7.0 requests | Standard Deviation 10.24 |
| VVZ-149 Injections | Total Number of Patient-controlled Analgesia (PCA) Requests for 12 Hours Post-dose | Time 6-8 Hour | 5.0 requests | Standard Deviation 5.97 |
| VVZ-149 Injections | Total Number of Patient-controlled Analgesia (PCA) Requests for 12 Hours Post-dose | Time 8-10 Hour | 4.6 requests | Standard Deviation 6.88 |
| Placebo | Total Number of Patient-controlled Analgesia (PCA) Requests for 12 Hours Post-dose | Time 4-6 Hour | 17.6 requests | Standard Deviation 63.54 |
| Placebo | Total Number of Patient-controlled Analgesia (PCA) Requests for 12 Hours Post-dose | Time 6-8 Hour | 10.1 requests | Standard Deviation 19.79 |
| Placebo | Total Number of Patient-controlled Analgesia (PCA) Requests for 12 Hours Post-dose | Time 8-10 Hour | 8.0 requests | Standard Deviation 16.18 |