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 a bunionectomy.
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 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 other foot surgery on the index foot * History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s) * Any prior surgery within 1 month before the first study drug * After Surgery: * Participant had a Type 3 deformity requiring a base wedge osteotomy or concomitant surgery such as hammertoe repair, or had medical complications 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 Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) 0 to 48 Hours (SPID48) 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). 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 |
|---|---|---|
| Percentage of Participants With at Least 30 Percent (%) Reduction in NPRS 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, HB/APAP or placebo was reported. |
| Percentage of Participants With at Least 50% Reduction in NPRS 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 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. |
| Time-Weighted SPID as Recorded on a NPRS 0 to 24 Hours (SPID24) 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). SPID24 was calculated from 0 to 24 hours and the score range was -240 (worst score) to 240 (best score). |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | Day 1 and Day 2 | — |
| Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | Day 1 and Day 2 | — |
| Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Day 16 | — |
| Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | Day 1 and Day 2 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to VX-548 and HB/APAP for 2 days. | 59 |
| HB/APAP Participants received HB 5 mg/ APAP 325 mg q6h for 2 days. | 60 |
| VX-548: Low Dose Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days. | 33 |
| VX-548: Mid Dose Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days. | 62 |
| VX-548: High Dose Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days. | 60 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal of Consent (not due to AE) | 1 | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | HB/APAP | VX-548: Low Dose | VX-548: Mid Dose | VX-548: High Dose | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 13.6 | 50.0 years STANDARD_DEVIATION 12.5 | 47.8 years STANDARD_DEVIATION 15.5 | 48.3 years STANDARD_DEVIATION 13.1 | 47.6 years STANDARD_DEVIATION 13.7 | 48.4 years STANDARD_DEVIATION 13.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 22 Participants | 6 Participants | 20 Participants | 21 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 38 Participants | 27 Participants | 42 Participants | 39 Participants | 188 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 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) | 6.9 units on a scale STANDARD_DEVIATION 1.7 | 6.9 units on a scale STANDARD_DEVIATION 1.9 | 6.9 units on a scale STANDARD_DEVIATION 1.8 | 6.6 units on a scale STANDARD_DEVIATION 1.8 | 6.7 units on a scale STANDARD_DEVIATION 1.7 | 6.8 units on a scale STANDARD_DEVIATION 1.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 13 Participants | 9 Participants | 17 Participants | 14 Participants | 66 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 44 Participants | 22 Participants | 44 Participants | 42 Participants | 193 Participants |
| Sex: Female, Male Female | 49 Participants | 50 Participants | 25 Participants | 57 Participants | 53 Participants | 234 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 8 Participants | 5 Participants | 7 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 60 | 0 / 33 | 0 / 62 | 0 / 60 |
| other Total, other adverse events | 12 / 59 | 13 / 60 | 2 / 33 | 7 / 62 | 9 / 60 |
| serious Total, serious adverse events | 0 / 59 | 0 / 60 | 0 / 33 | 0 / 62 | 0 / 60 |
Outcome results
Primary
Time-Weighted Sum of Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) 0 to 48 Hours (SPID48) 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). 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 Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) 0 to 48 Hours (SPID48) After the First Dose of Study Drug | 100.98 units on a scale | Standard Error 11.6 |
| HB/APAP | Time-Weighted Sum of Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) 0 to 48 Hours (SPID48) After the First Dose of Study Drug | 115.64 units on a scale | Standard Error 11.49 |
| VX-548: Low Dose | Time-Weighted Sum of Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) 0 to 48 Hours (SPID48) After the First Dose of Study Drug | 112.92 units on a scale | Standard Error 15.52 |
| VX-548: Mid Dose | Time-Weighted Sum of Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) 0 to 48 Hours (SPID48) After the First Dose of Study Drug | 86.87 units on a scale | Standard Error 11.33 |
| VX-548: High Dose | Time-Weighted Sum of Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) 0 to 48 Hours (SPID48) After the First Dose of Study Drug | 137.77 units on a scale | Standard Error 11.5 |
p-value: 0.3706ANCOVA
p-value: 0.5379ANCOVA
p-value: 0.3859ANCOVA
p-value: 0.0251ANCOVA
Secondary
Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite)
Time frame: Day 1 and Day 2
Population: PK analysis set included participants who received at least 1 dose of VX-548. Here, Number Analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | VX-548: Day 1 | 0.650 hour*mcg/ml (h*mcg/mL) | Standard Deviation 0.173 |
| Placebo | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | VX-548: Day 2 | 0.885 hour*mcg/ml (h*mcg/mL) | Standard Deviation 0.248 |
| Placebo | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | M6-548: Day 1 | 0.845 hour*mcg/ml (h*mcg/mL) | Standard Deviation 0.337 |
| Placebo | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | M6-548: Day 2 | 1.94 hour*mcg/ml (h*mcg/mL) | Standard Deviation 0.577 |
| HB/APAP | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | M6-548: Day 2 | 5.12 hour*mcg/ml (h*mcg/mL) | Standard Deviation 1.41 |
| HB/APAP | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | VX-548: Day 1 | 1.84 hour*mcg/ml (h*mcg/mL) | Standard Deviation 0.451 |
| HB/APAP | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | M6-548: Day 1 | 2.23 hour*mcg/ml (h*mcg/mL) | Standard Deviation 0.753 |
| HB/APAP | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | VX-548: Day 2 | 2.54 hour*mcg/ml (h*mcg/mL) | Standard Deviation 0.731 |
| VX-548: Low Dose | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | M6-548: Day 2 | 8.27 hour*mcg/ml (h*mcg/mL) | Standard Deviation 2.16 |
| VX-548: Low Dose | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | VX-548: Day 2 | 3.72 hour*mcg/ml (h*mcg/mL) | Standard Deviation 0.873 |
| VX-548: Low Dose | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | M6-548: Day 1 | 3.53 hour*mcg/ml (h*mcg/mL) | Standard Deviation 1.13 |
| VX-548: Low Dose | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite) | VX-548: Day 1 | 2.95 hour*mcg/ml (h*mcg/mL) | Standard Deviation 0.745 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite)
Time frame: Day 1 and Day 2
Population: Pharmacokinetic (PK) analysis set included participants who received at least 1 dose of VX-548. Here, Number Analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 1 | 0.119 micrograms/milliliter (mcg/mL) | Standard Deviation 0.0536 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 2 | 0.118 micrograms/milliliter (mcg/mL) | Standard Deviation 0.0426 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 1 | 0.0929 micrograms/milliliter (mcg/mL) | Standard Deviation 0.0363 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 2 | 0.183 micrograms/milliliter (mcg/mL) | Standard Deviation 0.052 |
| HB/APAP | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 2 | 0.483 micrograms/milliliter (mcg/mL) | Standard Deviation 0.13 |
| HB/APAP | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 1 | 0.311 micrograms/milliliter (mcg/mL) | Standard Deviation 0.0864 |
| HB/APAP | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 1 | 0.234 micrograms/milliliter (mcg/mL) | Standard Deviation 0.0781 |
| HB/APAP | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 2 | 0.337 micrograms/milliliter (mcg/mL) | Standard Deviation 0.0951 |
| VX-548: Low Dose | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 2 | 0.787 micrograms/milliliter (mcg/mL) | Standard Deviation 0.21 |
| VX-548: Low Dose | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 2 | 0.503 micrograms/milliliter (mcg/mL) | Standard Deviation 0.126 |
| VX-548: Low Dose | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 1 | 0.385 micrograms/milliliter (mcg/mL) | Standard Deviation 0.114 |
| VX-548: Low Dose | Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 1 | 0.523 micrograms/milliliter (mcg/mL) | Standard Deviation 0.193 |
Secondary
Percentage of Participants With at Least 30 Percent (%) Reduction in NPRS 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, HB/APAP or placebo was 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 48 Hours After the First Dose of Study Drug | 67.8 percentage of participants |
| HB/APAP | Percentage of Participants With at Least 30 Percent (%) Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 68.3 percentage of participants |
| VX-548: Low Dose | Percentage of Participants With at Least 30 Percent (%) Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 75.8 percentage of participants |
| VX-548: Mid Dose | Percentage of Participants With at Least 30 Percent (%) Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 62.9 percentage of participants |
| VX-548: High Dose | Percentage of Participants With at Least 30 Percent (%) Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 83.3 percentage of participants |
p-value: 0.9986Cochran-Mantel-Haenszel
p-value: 0.4446Cochran-Mantel-Haenszel
p-value: 0.5978Cochran-Mantel-Haenszel
p-value: 0.0479Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With at Least 50% Reduction in NPRS 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 48 Hours After the First Dose of Study Drug | 61.0 percentage of participants |
| HB/APAP | Percentage of Participants With at Least 50% Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 61.7 percentage of participants |
| VX-548: Low Dose | Percentage of Participants With at Least 50% Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 72.7 percentage of participants |
| VX-548: Mid Dose | Percentage of Participants With at Least 50% Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 56.5 percentage of participants |
| VX-548: High Dose | Percentage of Participants With at Least 50% Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 66.7 percentage of participants |
p-value: 0.9895Cochran-Mantel-Haenszel
p-value: 0.2731Cochran-Mantel-Haenszel
p-value: 0.6492Cochran-Mantel-Haenszel
p-value: 0.5119Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With at Least 70% Reduction in NPRS 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 48 Hours After the First Dose of Study Drug | 40.7 percentage of participants |
| HB/APAP | Percentage of Participants With at Least 70% Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 50.0 percentage of participants |
| VX-548: Low Dose | Percentage of Participants With at Least 70% Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 51.5 percentage of participants |
| VX-548: Mid Dose | Percentage of Participants With at Least 70% Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 38.7 percentage of participants |
| VX-548: High Dose | Percentage of Participants With at Least 70% Reduction in NPRS at 48 Hours After the First Dose of Study Drug | 51.7 percentage of participants |
p-value: 0.3158Cochran-Mantel-Haenszel
p-value: 0.3247Cochran-Mantel-Haenszel
p-value: 0.8424Cochran-Mantel-Haenszel
p-value: 0.2312Cochran-Mantel-Haenszel
Secondary
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Day 16
Population: Safety set included all participants who had 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 Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 23 Participants |
| Placebo | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| HB/APAP | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 25 Participants |
| HB/APAP | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| VX-548: Low Dose | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 7 Participants |
| VX-548: Low Dose | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| VX-548: Mid Dose | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| VX-548: Mid Dose | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 17 Participants |
| VX-548: High Dose | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with TEAEs | 18 Participants |
| VX-548: High Dose | Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite)
Time frame: Day 1 and Day 2
Population: PK analysis set included participants who received at least 1 dose of VX-548. Here, Number Analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 1 | 2.20 hours (h) |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 2 | 1.93 hours (h) |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 1 | 6.00 hours (h) |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 2 | 5.88 hours (h) |
| HB/APAP | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 2 | 4.28 hours (h) |
| HB/APAP | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 1 | 2.17 hours (h) |
| HB/APAP | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 1 | 5.95 hours (h) |
| HB/APAP | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 2 | 1.97 hours (h) |
| VX-548: Low Dose | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 2 | 4.20 hours (h) |
| VX-548: Low Dose | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 2 | 2.00 hours (h) |
| VX-548: Low Dose | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | M6-548: Day 1 | 6.02 hours (h) |
| VX-548: Low Dose | Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite) | VX-548: Day 1 | 2.09 hours (h) |
Secondary
Time-Weighted SPID as Recorded on a NPRS 0 to 24 Hours (SPID24) 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). 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-Weighted SPID as Recorded on a NPRS 0 to 24 Hours (SPID24) After the First Dose of Study Drug | 31.54 units on a scale | Standard Error 5.57 |
| HB/APAP | Time-Weighted SPID as Recorded on a NPRS 0 to 24 Hours (SPID24) After the First Dose of Study Drug | 40.95 units on a scale | Standard Error 5.52 |
| VX-548: Low Dose | Time-Weighted SPID as Recorded on a NPRS 0 to 24 Hours (SPID24) After the First Dose of Study Drug | 34.36 units on a scale | Standard Error 7.45 |
| VX-548: Mid Dose | Time-Weighted SPID as Recorded on a NPRS 0 to 24 Hours (SPID24) After the First Dose of Study Drug | 24.78 units on a scale | Standard Error 5.44 |
| VX-548: High Dose | Time-Weighted SPID as Recorded on a NPRS 0 to 24 Hours (SPID24) After the First Dose of Study Drug | 45.22 units on a scale | Standard Error 5.52 |
p-value: 0.2318ANCOVA
p-value: 0.7615ANCOVA
p-value: 0.387ANCOVA
p-value: 0.0823ANCOVA