Acute Pain
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of suzetrigine for acute pain after a bunionectomy.
Interventions
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Before Surgery * Participants scheduled to undergo a primary unilateral bunionectomy with distal first metatarsal osteotomy (i.e., Austin procedure) and internal fixation under regional anesthesia (Mayo and popliteal sciatic block) * After Surgery * Participant is lucid and able to follow commands * All analgesic guidelines were followed during and after the bunionectomy Key
Exclusion criteria
* Before Surgery * Prior history of bunionectomy or or other foot surgery on the index foot; or bunionectomy on the opposite foot * 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 type 3 deformity requiring a base wedge osteotomy, concomitant surgery such as hammertoe repair; or experienced medical complications during the bunionectomy * Participant had a medical complication during the bunionectomy 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 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. |
| 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 from baseline. |
| Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo | At 48 Hours After First Dose of Study Drug | 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. |
| Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP | From Baseline up to Day 19 | The percentage of participants 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. |
| 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 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). SPID24 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 2 days. | 216 |
| Hydrocodone Bitartrate/Acetaminophen (HB/APAP) Participants received HB 5 mg/ APAP 325 mg q6h for 2 days. | 431 |
| Suzetrigine (SUZ) Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days. | 426 |
| Total | 1,073 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 3 | 3 |
| Overall Study | Other non-compliance | 1 | 1 | 0 |
| Overall Study | Randomized but not dosed | 0 | 0 | 2 |
| Overall Study | Withdrawal of Consent (not due to AE | 4 | 8 | 5 |
Baseline characteristics
| Characteristic | Placebo | Total | Suzetrigine (SUZ) | Hydrocodone Bitartrate/Acetaminophen (HB/APAP) |
|---|---|---|---|---|
| Age, Continuous | 48.1 years STANDARD_DEVIATION 13.5 | 48.0 years STANDARD_DEVIATION 13.1 | 47.7 years STANDARD_DEVIATION 13.3 | 48.3 years STANDARD_DEVIATION 12.6 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 11 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 24 Participants | 9 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 48 Participants | 260 Participants | 116 Participants | 96 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 84 Participants | 364 Participants | 131 Participants | 149 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiracial | 0 Participants | 9 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 132 Participants | 709 Participants | 295 Participants | 282 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 5 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 160 Participants | 759 Participants | 285 Participants | 314 Participants |
| Sex: Female, Male Female | 187 Participants | 912 Participants | 366 Participants | 359 Participants |
| Sex: Female, Male Male | 29 Participants | 161 Participants | 60 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 216 | 0 / 431 | 0 / 426 |
| other Total, other adverse events | 51 / 216 | 113 / 431 | 72 / 426 |
| serious Total, serious adverse events | 0 / 216 | 0 / 431 | 0 / 426 |
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 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. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure.
| 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 | 70.6 units on a scale | Standard Error 6.3 |
| 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 Placebo | 99.9 units on a scale | Standard Error 4.5 |
p-value: 0.0002ANCOVA
Secondary
Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP
The percentage of participants 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. Data for this outcome measure was planned to be collected and analyzed only for the HB/APAP and SUZ group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP | 16.5 percentage of participants |
| Suzetrigine (SUZ) | Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP | 9.2 percentage of participants |
p-value: 0.0014Pearson'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.
Time frame: At 48 Hours After First Dose of Study Drug
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo | 53.2 percentage of participants |
| Suzetrigine (SUZ) | Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo | 61.7 percentage of participants |
p-value: 0.0343Cochran-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. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Using Rescue Medication From 0 to 48 Hours, SUZ Compared to Placebo | 85.6 percentage of participants |
| Suzetrigine (SUZ) | Percentage of Participants Using Rescue Medication From 0 to 48 Hours, SUZ Compared to Placebo | 85.4 percentage of participants |
p-value: 0.9143Cochran-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 | 76 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 | 0 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 | 180 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 | 0 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 | 132 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 | 0 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 from baseline.
Time frame: From Baseline Up to 48 Hours After First Dose of Study Drug
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to ≥1-Point Reduction in NPRS, SUZ Compared to Placebo | 61 minutes |
| Suzetrigine (SUZ) | Time to ≥1-Point Reduction in NPRS, SUZ Compared to Placebo | 60 minutes |
p-value: 0.1315Log 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.
Time frame: 0 to 48 Hours After First Dose of Study Drug
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Use of Rescue Medication, SUZ Compared to Placebo | 185 minutes |
| Suzetrigine (SUZ) | Time to First Use of Rescue Medication, SUZ Compared to Placebo | 157 minutes |
p-value: 0.8592Log 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.
Time frame: From Baseline Up to 48 Hours After First Dose of Study Drug
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.
| 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 | 240 minutes |
p-value: 0.0016Log 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 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). SPID24 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. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.
| 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 | 19.8 units on a scale | Standard Error 3 |
| Suzetrigine (SUZ) | Time-weighted SPID as Recorded on the NPRS From 0 to 24 Hours (SPID24), SUZ Compared to Placebo | 30.6 units on a scale | Standard Error 2.1 |
p-value: 0.0032ANCOVA
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. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure.
| 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 | 120.1 units on a scale | Standard Error 4.5 |
| 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 | 99.9 units on a scale | Standard Error 4.5 |
p-value: 0.0016ANCOVA
Secondary
Total Rescue Medication Usage, SUZ Compared to Placebo
Time frame: 0 to 48 Hours After First Dose of Study Drug
Population: FAS. Here Overall Number of Participants Analyzed signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Total Rescue Medication Usage, SUZ Compared to Placebo | 800 milligram |
| Suzetrigine (SUZ) | Total Rescue Medication Usage, SUZ Compared to Placebo | 800 milligram |
p-value: 0.0205Wilcoxon rank-sum