Acute Pain
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of VX-548 doses in treating acute pain after an abdominoplasty.
Interventions
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 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Before Surgery: * Participant scheduled to undergo an abdominoplasty without collateral procedures * After Surgery: * Participant is lucid and able to follow commands * All analgesic guidelines were followed during and after the abdominoplasty * Abdominoplasty procedure duration \<=3 hours without collateral procedures (for example., liposuction) Key
Exclusion criteria
* Before Surgery: * Prior history of abdominoplasty, intra-abdominal and/or pelvic surgery * History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s) * Any prior surgery within 1 month before the first study drug * After Surgery: * Participant had medical complications during the abdominoplasty that, in the opinion of the investigator, should preclude randomization * Participant had collateral procedures during the abdominoplasty 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) at Rest 0 to 48 Hours (SPIDr0-48) After the First Dose of Study Drug | 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 pain intensity score at given post-dose time points from the baseline pain intensity scores (using pain rating score range: 0= no pain to 10= worst possible pain). SPIDr0-48 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-weighted SPID as Recorded on an NPRS at Rest 0 to 24 Hours (SPIDr0-24) After the First Dose of Study Drug | 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 pain intensity score at given post-dose time points from the baseline pain intensity scores (using pain rating score range: 0= no pain to 10= worst possible pain). SPIDr0-24 was calculated from 0 to 24 hours and the score range was -240 (worst score) to 240 (best score). |
| Percentage of Participants With at Least 30 Percent (%),Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | From Baseline At 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 percentage of participants with at least 30% reduction from baseline in NPRS at 48 hours after the first dose of VX-548 or placebo were reported. |
| Percentage of Participants With at Least 50% Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | From Baseline At 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 percentage of participants with at least 50% reduction from baseline in NPRS at 48 hours after the first dose of VX-548, HB/APAP, or placebo were reported. |
| Percentage of Participants With at Least 70% Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | From Baseline at 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 percentage of participants with at least 70% reduction from baseline in NPRS at 48 hours after the first dose of VX-548,HB/APAP or placebo were reported. |
| 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 16 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to VX-548 and HB/APAP for 2 days. | 77 |
| HB/APAP Participants received HB 5 mg / APAP 325 mg q6h for 2 days. | 76 |
| VX-548: Low Dose Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days. | 74 |
| VX-548: High Dose Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days. | 76 |
| Total | 303 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 4 | 3 | 3 |
| Overall Study | Other | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal of consent (not due to AE) | 0 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | VX-548: High Dose | VX-548: Low Dose | HB/APAP | Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 43.2 years STANDARD_DEVIATION 9.9 | 43.1 years STANDARD_DEVIATION 9.7 | 41.5 years STANDARD_DEVIATION 9.2 | 45.4 years STANDARD_DEVIATION 10.7 | 42.6 years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 80 Participants | 25 Participants | 21 Participants | 20 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 223 Participants | 51 Participants | 53 Participants | 56 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pain Intensity at Baseline (at 0 hours) as Recorded on Numeric Pain Rating Scale (NPRS) | 7.3 units on a scale STANDARD_DEVIATION 1.7 | 7.2 units on a scale STANDARD_DEVIATION 1.7 | 7.4 units on a scale STANDARD_DEVIATION 1.8 | 7.3 units on a scale STANDARD_DEVIATION 1.8 | 7.4 units on a scale STANDARD_DEVIATION 1.6 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 66 Participants | 13 Participants | 15 Participants | 18 Participants | 20 Participants |
| Race/Ethnicity, Customized Multiracial | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 4 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 224 Participants | 57 Participants | 57 Participants | 53 Participants | 57 Participants |
| Sex: Female, Male Female | 298 Participants | 75 Participants | 74 Participants | 73 Participants | 76 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 76 | 0 / 74 | 0 / 76 |
| other Total, other adverse events | 40 / 77 | 37 / 76 | 37 / 74 | 33 / 76 |
| serious Total, serious adverse events | 1 / 77 | 1 / 76 | 1 / 74 | 0 / 76 |
Outcome results
Primary
Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) at Rest 0 to 48 Hours (SPIDr0-48) After the 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 pain intensity score at given post-dose time points from the baseline pain intensity scores (using pain rating score range: 0= no pain to 10= worst possible pain). SPIDr0-48 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) at Rest 0 to 48 Hours (SPIDr0-48) After the First Dose of Study Drug | 72.73 units on a scale | Standard Error 10.23 |
| HB/APAP | Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) at Rest 0 to 48 Hours (SPIDr0-48) After the First Dose of Study Drug | 85.20 units on a scale | Standard Error 10.3 |
| VX-548: Low Dose | Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) at Rest 0 to 48 Hours (SPIDr0-48) After the First Dose of Study Drug | 95.11 units on a scale | Standard Error 10.44 |
| VX-548: High Dose | Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) at Rest 0 to 48 Hours (SPIDr0-48) After the First Dose of Study Drug | 110.53 units on a scale | Standard Error 10.3 |
p-value: 0.3914ANCOVA
p-value: 0.1266ANCOVA
p-value: 0.0097ANCOVA
Secondary
Percentage of Participants With at Least 30 Percent (%),Reduction in NPRS (at Rest) at 48 Hours After the 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 percentage of participants with at least 30% reduction from baseline in NPRS at 48 hours after the first dose of VX-548 or placebo were reported.
Time frame: From Baseline At 48 Hours After First Dose of Study Drug
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With at Least 30 Percent (%),Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 48.1 percentage of participants |
| HB/APAP | Percentage of Participants With at Least 30 Percent (%),Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 53.9 percentage of participants |
| VX-548: Low Dose | Percentage of Participants With at Least 30 Percent (%),Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 59.5 percentage of participants |
| VX-548: High Dose | Percentage of Participants With at Least 30 Percent (%),Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 60.5 percentage of participants |
p-value: 0.4712Cochran-Mantel-Haenszel
p-value: 0.1635Cochran-Mantel-Haenszel
p-value: 0.1158Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With at Least 50% Reduction in NPRS (at Rest) at 48 Hours After the 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 percentage of participants with at least 50% reduction from baseline in NPRS at 48 hours after the first dose of VX-548, HB/APAP, or placebo were reported.
Time frame: From Baseline At 48 Hours After First Dose of Study Drug
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With at Least 50% Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 33.8 percentage of participants |
| HB/APAP | Percentage of Participants With at Least 50% Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 42.1 percentage of participants |
| VX-548: Low Dose | Percentage of Participants With at Least 50% Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 43.2 percentage of participants |
| VX-548: High Dose | Percentage of Participants With at Least 50% Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 44.7 percentage of participants |
p-value: 0.2882Cochran-Mantel-Haenszel
p-value: 0.2344Cochran-Mantel-Haenszel
p-value: 0.1724Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With at Least 70% Reduction in NPRS (at Rest) at 48 Hours After the 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 percentage of participants with at least 70% reduction from baseline in NPRS at 48 hours after the first dose of VX-548,HB/APAP or placebo were reported.
Time frame: From Baseline at 48 Hours After First Dose of Study Drug
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With at Least 70% Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 14.3 percentage of participants |
| HB/APAP | Percentage of Participants With at Least 70% Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 23.7 percentage of participants |
| VX-548: Low Dose | Percentage of Participants With at Least 70% Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 18.9 percentage of participants |
| VX-548: High Dose | Percentage of Participants With at Least 70% Reduction in NPRS (at Rest) at 48 Hours After the First Dose of Study Drug | 25.0 percentage of participants |
p-value: 0.1343Cochran-Mantel-Haenszel
p-value: 0.4501Cochran-Mantel-Haenszel
p-value: 0.1009Cochran-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 16
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 | 54 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 | 1 Participants |
| HB/APAP | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| HB/APAP | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 46 Participants |
| VX-548: Low Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 45 Participants |
| VX-548: Low Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 1 Participants |
| VX-548: High Dose | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 42 Participants |
| VX-548: High Dose | 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-weighted SPID as Recorded on an NPRS at Rest 0 to 24 Hours (SPIDr0-24) After the 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 pain intensity score at given post-dose time points from the baseline pain intensity scores (using pain rating score range: 0= no pain to 10= worst possible pain). SPIDr0-24 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 an NPRS at Rest 0 to 24 Hours (SPIDr0-24) After the First Dose of Study Drug | 25.96 units on a scale | Standard Error 4.7 |
| HB/APAP | Time-weighted SPID as Recorded on an NPRS at Rest 0 to 24 Hours (SPIDr0-24) After the First Dose of Study Drug | 29.98 units on a scale | Standard Error 4.73 |
| VX-548: Low Dose | Time-weighted SPID as Recorded on an NPRS at Rest 0 to 24 Hours (SPIDr0-24) After the First Dose of Study Drug | 37.65 units on a scale | Standard Error 4.79 |
| VX-548: High Dose | Time-weighted SPID as Recorded on an NPRS at Rest 0 to 24 Hours (SPIDr0-24) After the First Dose of Study Drug | 45.54 units on a scale | Standard Error 4.73 |
p-value: 0.5476ANCOVA
p-value: 0.0825ANCOVA
p-value: 0.0036ANCOVA