Acute Pain
Conditions
Brief summary
The purpose of this study was to evaluate the efficacy and safety of Suzetrigine (SUZ) in treating acute pain after an abdominoplasty.
Interventions
Tablets for oral administration.
DRUGHB/APAP
Capsules for oral administration.
Placebo matched to SUZ for oral administration.
Placebo matched to HB/APAP for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
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 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Before Surgery * Participant scheduled to undergo a standard (full) abdominoplasty procedure * After Surgery * Participant is lucid and able to follow commands and able to swallow oral medications * All analgesic guidelines were followed during and after the abdominoplasty * Abdominoplasty procedure duration less than or equal to (≤3) hours Key
Exclusion criteria
* Before Surgery * Prior history of abdominoplasty * History of Intra-abdominal and/or pelvic surgery that resulted into complications * History of cardiac dysrhythmias within the last 2 years requiring anti-arrhythmia treatment(s) * Any prior surgery within 1 month before the first study drug dose * After Surgery * Participant had a non standard abdominoplasty, collateral procedures during the abdominoplasty or any surgical complications during the abdominoplasty * Participant had a medical complication during the abdominoplasty that, in the opinion of the investigator, should preclude randomization Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to Placebo | 0 to 48 hours After First Dose of Study Drug | SPID was calculated as the sum of the product of time (in hours) elapsed since previous measurements and pain intensity difference. Pain intensity difference was calculated by subtracting the baseline pain intensity score from the pain intensity score at each postdose time point (using pain rating score range: 0 =no pain to 10 =worst possible pain). SPID48 was calculated from 0 to 48 hours and the score range was -480 (worst score) to 480 (best score). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Greater Than or Equal to (≥) 2-point Reduction in NPRS, SUZ Compared to Placebo | From Baseline Up to 48 Hours After First Dose of Study Drug | Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The time to ≥2-point reduction in NPRS from baseline was the time elapsed from the first dose of study drug until the first time the participant had at least a 2-point reduction in NPRS scores from baseline. Participants who did not reach at least a 2-point reduction in NPRS from baseline by 48 hours were censored at 48 hours. |
| Time to ≥1-point Reduction in NPRS, SUZ Compared to Placebo | From Baseline Up to 48 Hours After First Dose of Study Drug | Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The time to ≥1-point reduction in NPRS from baseline was the time elapsed from the first dose of study drug until the first time the participant had at least a 1-point reduction in NPRS scores from baseline. Participants who did not reach at least a 1-point reduction in NPRS from baseline by 48 hours were censored at 48 hours. |
| Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo | At 48 hours | The PGA is a single-item assessment of patient perceptions of the method of pain control with the study drug and is evaluated on a 4-point Likert scale as: (poor, fair, good, or excellent). Percentage of participants who reported good or excellent on the PGA scale were reported. Participants who discontinued study drug or had missing PGA at 48 hours were considered to not have reported good or excellent on the PGA. |
| Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP | From Baseline Up to Day 19 | The incidence with the events of vomiting or nausea during the specified time frame was reported. |
| Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to HB/APAP | 0 to 48 hours After First Dose of Study Drug | SPID was calculated as the sum of the product of time (in hours) elapsed since previous measurements and pain intensity difference. Pain intensity difference was calculated by subtracting the baseline pain intensity score from the pain intensity score at each post dose time point (using pain rating score range: 0 =no pain to 10 =worst possible pain). SPID48 was calculated from 0 to 48 hours and the score range was -480 (worst score) to 480 (best score). |
| Time to First Use of Rescue Medication, SUZ Compared to Placebo | 0 to 48 Hours After First Dose of Study Drug | Time to first use of rescue medication is the time from the first dose of study drug until the first use of rescue medication. Participants who did not take any rescue medication within 48 hours were censored at 48 hours. |
| Percentage of Participants Using Rescue Medication From 0 to 48 Hours, SUZ Compared to Placebo | 0 to 48 Hours After First Dose of Study Drug | — |
| Total Rescue Medication Usage, SUZ Compared to Placebo | 0 to 48 Hours After First Dose of Study Drug | — |
| Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Day 1 up to Day 19 | — |
| Time-weighted SPID as Recorded on the NPRS From 0 to 24 Hours (SPID24), SUZ Compared to Placebo | 0 to 24 Hours After First Dose of Study Drug | SPID was calculated as the sum of the product of time (in hours) elapsed since previous measurements and pain intensity difference. Pain intensity difference (PID) was calculated by subtracting the baseline pain intensity score from the pain intensity score at each post dose time point (NPRS range: 0 = no pain to 10 = worst possible pain). Time-weighted SPID was calculated as the sum of the PIDs at each post-dose time point multiplied by the time interval (in hours) between each time point. SPID 24 was calculated from 0 to 24 hours and the score range was -240 (worst score) to 240 (best score). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to SUZ and HB/APAP for 48 hours. | 223 |
| Hydrocodone Bitartrate/Acetaminophen (HB/APAP) Participants received HB 5 mg/ APAP 325 mg q6h for 48 hours. | 448 |
| Suzetrigine (SUZ) Participants received SUZ (100 mg as first dose, followed by 50 mg q12h) for 48 hours. | 447 |
| Total | 1,118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 10 | 17 | 19 |
| Overall Study | Other | 1 | 0 | 1 |
| Overall Study | Other non-compliance | 0 | 1 | 2 |
| Overall Study | Sponsor Decision | 1 | 0 | 0 |
| Overall Study | Withdrawal of consent (not due to AE) | 3 | 2 | 2 |
Baseline characteristics
| Characteristic | Hydrocodone Bitartrate/Acetaminophen (HB/APAP) | Suzetrigine (SUZ) | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 8.7 | 41.5 years STANDARD_DEVIATION 9.1 | 41.5 years STANDARD_DEVIATION 8.5 | 41.8 years STANDARD_DEVIATION 8.8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 5 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 7 Participants | 0 Participants | 16 Participants |
| Race/Ethnicity, Customized Black or African American | 114 Participants | 123 Participants | 62 Participants | 299 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 157 Participants | 150 Participants | 73 Participants | 380 Participants |
| Race/Ethnicity, Customized Missing | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Multiracial | 4 Participants | 2 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 5 Participants | 3 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 288 Participants | 297 Participants | 150 Participants | 735 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 316 Participants | 307 Participants | 155 Participants | 778 Participants |
| Sex: Female, Male Female | 441 Participants | 437 Participants | 220 Participants | 1098 Participants |
| Sex: Female, Male Male | 7 Participants | 10 Participants | 3 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 222 | 0 / 448 | 0 / 448 |
| other Total, other adverse events | 94 / 222 | 201 / 448 | 146 / 448 |
| serious Total, serious adverse events | 5 / 222 | 7 / 448 | 11 / 448 |
Outcome results
Primary
Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to Placebo
SPID was calculated as the sum of the product of time (in hours) elapsed since previous measurements and pain intensity difference. Pain intensity difference was calculated by subtracting the baseline pain intensity score from the pain intensity score at each postdose time point (using pain rating score range: 0 =no pain to 10 =worst possible pain). SPID48 was calculated from 0 to 48 hours and the score range was -480 (worst score) to 480 (best score).
Time frame: 0 to 48 hours After First Dose of Study Drug
Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to Placebo | 70.1 units on a scale | Standard Error 6.1 |
| Suzetrigine (SUZ) | Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to Placebo | 118.4 units on a scale | Standard Error 4.3 |
p-value: <0.0001ANCOVA
Secondary
Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP
The incidence with the events of vomiting or nausea during the specified time frame was reported.
Time frame: From Baseline Up to Day 19
Population: Safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP | 33.5 percentage of participants |
| Suzetrigine (SUZ) | Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP | 20.3 percentage of participants |
p-value: <0.0001Pearson's chi-squared test
Secondary
Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo
The PGA is a single-item assessment of patient perceptions of the method of pain control with the study drug and is evaluated on a 4-point Likert scale as: (poor, fair, good, or excellent). Percentage of participants who reported good or excellent on the PGA scale were reported. Participants who discontinued study drug or had missing PGA at 48 hours were considered to not have reported good or excellent on the PGA.
Time frame: At 48 hours
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo | 49.8 percentage of participants |
| Suzetrigine (SUZ) | Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo | 67.8 percentage of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Using Rescue Medication From 0 to 48 Hours, SUZ Compared to Placebo
Time frame: 0 to 48 Hours After First Dose of Study Drug
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Using Rescue Medication From 0 to 48 Hours, SUZ Compared to Placebo | 87.9 percentage of participants |
| Suzetrigine (SUZ) | Percentage of Participants Using Rescue Medication From 0 to 48 Hours, SUZ Compared to Placebo | 81.0 percentage of participants |
p-value: 0.0237Cochran-Mantel-Haenszel
Secondary
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Day 19
Population: Safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 125 Participants |
| Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 5 Participants |
| Suzetrigine (SUZ) | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 272 Participants |
| Suzetrigine (SUZ) | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 7 Participants |
| Suzetrigine (SUZ) | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 224 Participants |
| Suzetrigine (SUZ) | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 11 Participants |
Secondary
Time to ≥1-point Reduction in NPRS, SUZ Compared to Placebo
Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The time to ≥1-point reduction in NPRS from baseline was the time elapsed from the first dose of study drug until the first time the participant had at least a 1-point reduction in NPRS scores from baseline. Participants who did not reach at least a 1-point reduction in NPRS from baseline by 48 hours were censored at 48 hours.
Time frame: From Baseline Up to 48 Hours After First Dose of Study Drug
Population: FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to ≥1-point Reduction in NPRS, SUZ Compared to Placebo | 91 minutes |
| Suzetrigine (SUZ) | Time to ≥1-point Reduction in NPRS, SUZ Compared to Placebo | 34 minutes |
p-value: <0.0001Log Rank
Secondary
Time to First Use of Rescue Medication, SUZ Compared to Placebo
Time to first use of rescue medication is the time from the first dose of study drug until the first use of rescue medication. Participants who did not take any rescue medication within 48 hours were censored at 48 hours.
Time frame: 0 to 48 Hours After First Dose of Study Drug
Population: FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Use of Rescue Medication, SUZ Compared to Placebo | 115 minutes |
| Suzetrigine (SUZ) | Time to First Use of Rescue Medication, SUZ Compared to Placebo | 186 minutes |
p-value: <0.0001Log Rank
Secondary
Time to Greater Than or Equal to (≥) 2-point Reduction in NPRS, SUZ Compared to Placebo
Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The time to ≥2-point reduction in NPRS from baseline was the time elapsed from the first dose of study drug until the first time the participant had at least a 2-point reduction in NPRS scores from baseline. Participants who did not reach at least a 2-point reduction in NPRS from baseline by 48 hours were censored at 48 hours.
Time frame: From Baseline Up to 48 Hours After First Dose of Study Drug
Population: FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Greater Than or Equal to (≥) 2-point Reduction in NPRS, SUZ Compared to Placebo | 480 minutes |
| Suzetrigine (SUZ) | Time to Greater Than or Equal to (≥) 2-point Reduction in NPRS, SUZ Compared to Placebo | 119 minutes |
p-value: <0.0001Log Rank
Secondary
Time-weighted SPID as Recorded on the NPRS From 0 to 24 Hours (SPID24), SUZ Compared to Placebo
SPID was calculated as the sum of the product of time (in hours) elapsed since previous measurements and pain intensity difference. Pain intensity difference (PID) was calculated by subtracting the baseline pain intensity score from the pain intensity score at each post dose time point (NPRS range: 0 = no pain to 10 = worst possible pain). Time-weighted SPID was calculated as the sum of the PIDs at each post-dose time point multiplied by the time interval (in hours) between each time point. SPID 24 was calculated from 0 to 24 hours and the score range was -240 (worst score) to 240 (best score).
Time frame: 0 to 24 Hours After First Dose of Study Drug
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-weighted SPID as Recorded on the NPRS From 0 to 24 Hours (SPID24), SUZ Compared to Placebo | 24.2 units on a scale | Standard Error 2.8 |
| Suzetrigine (SUZ) | Time-weighted SPID as Recorded on the NPRS From 0 to 24 Hours (SPID24), SUZ Compared to Placebo | 48.0 units on a scale | Standard Error 2 |
p-value: <0.0001ANCOVA
Secondary
Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to HB/APAP
SPID was calculated as the sum of the product of time (in hours) elapsed since previous measurements and pain intensity difference. Pain intensity difference was calculated by subtracting the baseline pain intensity score from the pain intensity score at each post dose time point (using pain rating score range: 0 =no pain to 10 =worst possible pain). SPID48 was calculated from 0 to 48 hours and the score range was -480 (worst score) to 480 (best score).
Time frame: 0 to 48 hours After First Dose of Study Drug
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to HB/APAP | 111.8 units on a scale | Standard Error 4.3 |
| Suzetrigine (SUZ) | Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48) SUZ Compared to HB/APAP | 118.4 units on a scale | Standard Error 4.3 |
p-value: 0.2781ANCOVA
Secondary
Total Rescue Medication Usage, SUZ Compared to Placebo
Time frame: 0 to 48 Hours After First Dose of Study Drug
Population: FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Total Rescue Medication Usage, SUZ Compared to Placebo | 1200 milligram |
| Suzetrigine (SUZ) | Total Rescue Medication Usage, SUZ Compared to Placebo | 800 milligram |
p-value: 0.008Wilcoxon rank-sum