A Study Evaluating Efficacy and Safety of VX-548 for Acut... | NCT04977336

NCT04977336

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received placebo matched to VX-548 and Hydrocodone bitartrate/acetaminophen (HB/APAP) for 2 days.	Drug: Placebo (matched to VX-548) Drug: Placebo (matched to HB/APAP)
HB/APAP	Active Comparator	Participants received HB 5 milligrams (mg)/ APAP 325 mg every 6 hours (q6h) for 2 days.	Drug: HB/APAP
VX-548: Low Dose	Experimental	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg tablet every 12 hours (q12h) for 2 days.	Drug: VX-548
VX-548: Mid Dose	Experimental	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.	Drug: VX-548
VX-548: High Dose	Experimental	Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.	Drug: VX-548

Name	Type	Description	Arm Group Labels	Other Names
VX-548	Drug	Tablets for oral administration.	VX-548: High Dose VX-548: Low Dose VX-548: Mid Dose

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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).	0 to 48 hours After First Dose of Study Drug

Secondary Outcomes

Measure	Description	Time Frame
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).

Eligibility Module

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Shoals Medical Trials Inc.		Sheffield	Alabama	35660	United States
Arizona Research Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37530822	Derived	Jones J, Correll DJ, Lechner SM, Jazic I, Miao X, Shaw D, Simard C, Osteen JD, Hare B, Beaton A, Bertoch T, Buvanendran A, Habib AS, Pizzi LJ, Pollak RA, Weiner SG, Bozic C, Negulescu P, White PF; VX21-548-101 and VX21-548-102 Trial Groups. Selective Inhibition of NaV1.8 with VX-548 for Acute Pain. N Engl J Med. 2023 Aug 3;389(5):393-405. doi: 10.1056/NEJMoa2209870.
35580314

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received placebo matched to VX-548 and Hydrocodone bitartrate/acetaminophen (HB/APAP) for 2 days.
FG001	HB/APAP	Participants received HB 5 milligrams (mg)/ APAP 325 mg every 6 hours (q6h) for 2 days.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 21, 2022	Feb 14, 2025

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug.

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received placebo matched to VX-548 and HB/APAP for 2 days.
BG001	HB/APAP	Participants received HB 5 mg/ APAP 325 mg q6h for 2 days.
BG002	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.
BG003	VX-548: Mid Dose	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.
BG004	VX-548: High Dose	Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG00059 BG00160 BG00233 BG00362 BG00460 BG005274

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00047.8± 13.6 BG00150.0± 12.5 BG00247.8± 15.5 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00049 BG00150 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00017 BG00122 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0010 BG002

Pain Intensity at Baseline (at 0 hours) as Recorded on Numeric Pain Rating Scale (NPRS)

Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0=no pain and 10=worst imaginable pain.

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG0006.9± 1.7 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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).

Full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug.

Posted

Least Squares Mean

Standard Error

units on a scale

0 to 48 hours After First Dose of Study Drug

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-548 and HB/APAP for 2 days.
OG001	HB/APAP	Participants received HB 5 mg/ APAP 325 mg every q6h for 2 days.
OG002	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.
OG003	VX-548: Mid Dose	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.
OG004	VX-548: High Dose	Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.

Units	Counts
Participants	OG00059 OG00160 OG00233 OG003

Title

Denominators

Categories

Title	Measurements
	OG000100.98± 11.60 OG001115.64± 11.49 OG002112.92± 15.52 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.3706														Superiority
OG000 OG002		ANCOVA		0.5379

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).

FAS.

Posted

Least Squares Mean

Standard Error

units on a scale

0 to 24 hours After First Dose of Study Drug

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-548 and HB/APAP for 2 days.
OG001	HB/APAP	Participants received HB 5 mg/ APAP 325 mg capsule q6h for 2 days.
OG002	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.
OG003	VX-548: Mid Dose

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.

FAS.

Posted

Number

percentage of participants

From Baseline at 48 Hours After First Dose of Study Drug

ID	Title	Description
OG000	Placebo	Participants received placebo and HB/APAP for 2 days.
OG001	HB/APAP	Participants received HB 5 mg/ APAP 325 mg q6h for 2 days.
OG002	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.
OG003	VX-548: Mid Dose	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.

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.

FAS.

Posted

Number

percentage of participants

From Baseline at 48 Hours After First Dose of Study Drug

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-548 and HB/APAP for 2 days.
OG001	HB/APAP	Participants received HB 5 mg/ APAP 325 mg q6h for 2 days.
OG002	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.
OG003	VX-548: Mid Dose	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.

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.

FAS.

Posted

Number

percentage of participants

From Baseline at 48 Hours After First Dose of Study Drug

ID	Title	Description
OG000	Placebo	Participants received placebo and HB/APAP for 2 days.
OG001	HB/APAP	Participants received HB 5 mg/ APAP 325 mg q6h 2 days.
OG002	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.
OG003	VX-548: Mid Dose	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.

Secondary

Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite)

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.

Posted

Mean

Standard Deviation

micrograms/milliliter (mcg/mL)

Day 1 and Day 2

ID	Title	Description
OG000	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.
OG001	VX-548: Mid Dose	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.
OG002	VX-548: High Dose	Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.

Units	Counts
Participants

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite)

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.

Posted

Median

Full Range

hours (h)

Day 1 and Day 2

ID	Title	Description
OG000	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.
OG001	VX-548: Mid Dose	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.
OG002	VX-548: High Dose	Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.

Units	Counts
Participants

Secondary

Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite)

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.

Posted

Mean

Standard Deviation

hour*mcg/ml (h*mcg/mL)

Day 1 and Day 2

ID	Title	Description
OG000	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.
OG001	VX-548: Mid Dose	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.
OG002	VX-548: High Dose	Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.

Units	Counts
Participants

Secondary

Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Safety set included all participants who had received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Day 1 up to Day 16

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-548 and HB/APAP for 2 days.
OG001	HB/APAP	Participants received HB/APAP 5 mg/ APAP 325 mg q6h for 2 days.
OG002	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.
OG003	VX-548: Mid Dose	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.
OG004	VX-548: High Dose	Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo matched to VX-548 and HB/APAP for 2 days.	59	59	12	59
EG001	HB/APAP	Participants received HB 5 mg/ APAP 325 mg q6h for 2 days.	60	60	13	60
EG002	VX-548: Low Dose	Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg q12h for 2 days.	33	33	2	33
EG003	VX-548: Mid Dose	Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.	62	62	7	62
EG004	VX-548: High Dose	Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.	60	60	9	60

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0005 affected59 at risk EG00111 affected60 at risk EG0022 affected33 at risk EG0033 affected62 at risk EG0045 affected60 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected59 at risk EG0013 affected60 at risk EG0020 affected33 at risk EG003
Headache	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0007 affected59 at risk EG0014 affected60 at risk EG0020 affected33 at risk EG003

ID	Term
D059787	Acute Pain

EG0040 affected60 at risk

EG0045 affected60 at risk

OG0011.97(0.850 to 6.00)

OG0022.00(0.667 to 5.98)

OG0015.95(2.00 to 12.2)

OG0026.02(1.92 to 12.1)

OG0014.28(1.00 to 12.0)

OG0024.20(1.70 to 12.0)

ID	Term
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms