A Dose-ranging Study to Evaluate Efficacy and Safety of V... | NCT03764072

A Dose-ranging Study to Evaluate Efficacy and Safety of V... | NCT03764072 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received placebo matched to VX-150 for 2 days.	Drug: Placebo
VX-150 - Dose Level 1	Experimental	Participants received VX-150 1500 milligrams (mg) as first dose, followed by VX-150 750 mg every 12 hours (q12h) for 2 days.	Drug: VX-150
VX-150 - Dose Level 2	Experimental	Participants received VX-150 1000 mg once daily (qd) for 2 days.	Drug: VX-150
VX-150 - Dose Level 3	Experimental	Participants received VX-150 500 mg q12h for 2 days.	Drug: VX-150
VX-150 - Dose Level 4	Experimental	Participants received VX-150 500 mg as first dose, followed by VX-150 250 mg q12h for 2 days.	Drug: VX-150
VX-150 - Dose Level 5	Experimental	Participants received VX-150 250 mg qd for 2 days.

Name	Type	Description	Arm Group Labels	Other Names
VX-150	Drug	Capsules for oral administration.	VX-150 - Dose Level 1 VX-150 - Dose Level 2 VX-150 - Dose Level 3 VX-150 - Dose Level 4

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose	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).	0 to 24 Hours After First Dose

Secondary Outcomes

Measure	Description	Time Frame
Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose	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).

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Research Center		Phoenix	Arizona	85053	United States
Anaheim Clinical Trials

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received placebo matched to VX-150 for 2 days.
FG001	VX-150 - Dose Level 1	Participants received VX-150 1500 milligrams (mg) as first dose, followed by VX-150 750 mg every 12 hours (q12h) for 2 days.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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	Sep 26, 2018	Jan 3, 2022

Type	Comment	Reasons
Withdrawal of consent (due to lack of efficacy)		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects FG0040 subjects FG0050 subjects
Withdrawal of consent (for other reason)		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
Lost to Follow-up		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received placebo matched to VX-150 for 2 days.
BG001	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
BG002	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
BG003	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.
BG004	VX-150 - Dose Level 4	Participants received VX-150 500 mg as first dose, followed by VX-150 250 mg q12h for 2 days.
BG005	VX-150 - Dose Level 5	Participants received VX-150 250 mg qd for 2 days.
BG006	Total	Total of all reporting groups

Units	Counts
Participants	BG00046 BG00142 BG00244 BG00345 BG00446 BG00527 BG006250

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
	BG00046.5± 14.21 BG00144.6± 13.03 BG00244.7± 13.23 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00040 BG00137 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00016 BG00114 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0011 BG002

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

Pain intensity was recorded on 11-point ordinal 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
	BG0006.5± 1.8 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 the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose

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).

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

Posted

Mean

Standard Deviation

units on a scale

0 to 24 Hours After First Dose

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-150 for 2 days.
OG001	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
OG002	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
OG003	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.
OG004	VX-150 - Dose Level 4	Participants received VX-150 500 mg as first dose, followed by VX-150 250 mg q12h for 2 days.
OG005	VX-150 - Dose Level 5	Participants received VX-150 250 mg qd for 2 days.

Units	Counts
Participants	OG00046 OG00142 OG00244 OG003

Title

Denominators

Categories

Title	Measurements
	OG00019.1± 49.7 OG00137.3± 45.6 OG00232.3± 51.2 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 OG002 OG003 OG004 OG005		Multiple Comparison Procedure-Modelling		0.2107	Dose response Model - Linear													Superiority
OG000 OG001 OG002 OG003 OG004 OG005

Secondary

Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose

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).

FAS.

Posted

Least Squares Mean

Standard Deviation

units on a scale

0 to 48 Hours After First Dose

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-150 for 2 days.
OG001	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
OG002	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
OG003	VX-150 - Dose Level 3

Secondary

Proportion of Participants With at Least 30 Percent (%) Reduction in NPRS at 24 Hours After First Dose of VX-150 Versus Placebo

Pain intensity was recorded on 11-point ordinal 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 24 hours after the first dose of VX-150 or placebo were reported.

FAS.

Posted

Number

percentage of participants

From Baseline at 24 Hours After First Dose

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-150 for 2 days.
OG001	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
OG002	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
OG003	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.

Secondary

Proportion of Participants With at Least 50% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo

Pain intensity was recorded on 11-point ordinal 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 24 hours after the first dose of VX-150 or placebo were reported.

FAS.

Posted

Number

percentage of participants

From Baseline at 24 Hours After First Dose

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-150 for 2 days.
OG001	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
OG002	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
OG003	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.

Secondary

Proportion of Participants With at Least 70% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo

Pain intensity was recorded on 11-point ordinal 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 24 hours after the first dose of VX-150 or placebo were reported.

FAS.

Posted

Number

percentage of participants

From Baseline at 24 Hours After First Dose

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-150 for 2 days.
OG001	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
OG002	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
OG003	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.

Secondary

Time to Onset of Confirmed Perceptible Pain Relief After First Dose of VX-150 Versus Placebo

Time to onset of confirmed perceptible pain relief (time to onset of perceptible pain relief [any pain relief at all after the first dose] for participants who had meaningful pain relief [relief that is meaningful to participants after the first dose] reported based on the stopwatch assessment.

FAS.

Posted

Median

Full Range

minutes

Up to 6 hours After the First Dose

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-150 for 2 days.
OG001	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
OG002	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
OG003	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.

Secondary

Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo

Time to onset of meaningful pain relief (relief that is meaningful to participants after the first dose) reported based on the stopwatch assessment.

FAS.

Posted

Median

Full Range

minutes

Up to 6 Hours After the First Dose

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-150 for 2 days.
OG001	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
OG002	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
OG003	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.
OG004	VX-150 - Dose Level 4

Secondary

Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5)

Pharmacokinetic (PK) set included all randomized participants who received at least 1 dose of study drug. Here, "number analyzed" signifies those participants who were evaluable at specified time points.

Posted

Mean

Standard Deviation

micrograms per milliliter (mcg/mL)

Day 1 and Day 2

ID	Title	Description
OG000	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
OG001	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
OG002	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.
OG003	VX-150 - Dose Level 4	Participants received VX-150 500 mg as first dose, followed by VX-150 250 mg q12h for 2 days.
OG004	VX-150 - Dose Level 5

Secondary

Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114

PK set. Here, "number analyzed" signifies those participants who were evaluable at specified time points.

Posted

Mean

Standard Deviation

microgram*hour per milliliter (mcg*h/mL)

Day 1 and Day 2

ID	Title	Description
OG000	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
OG001	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
OG002	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.
OG003	VX-150 - Dose Level 4	Participants received VX-150 500 mg as first dose, followed by VX-150 250 mg q12h for 2 days.
OG004	VX-150 - Dose Level 5

Secondary

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

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

Posted

Number

participants

Day 1 up to Day 10

ID	Title	Description
OG000	Placebo	Participants received placebo matched to VX-150 for 2 days.
OG001	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
OG002	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.
OG003	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.
OG004	VX-150 - Dose Level 4	Participants received VX-150 500 mg as first dose, followed by VX-150 250 mg q12h for 2 days.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo matched to VX-150 for 2 days.	46	0	46	7	46
EG001	VX-150 - Dose Level 1	Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.	42	0	42	9	42
EG002	VX-150 - Dose Level 2	Participants received VX-150 1000 mg qd for 2 days.	44	0	44	13	44
EG003	VX-150 - Dose Level 3	Participants received VX-150 500 mg q12h for 2 days.	45	0	45	12	45
EG004	VX-150 - Dose Level 4	Participants received VX-150 500 mg as first dose, followed by VX-150 250 mg q12h for 2 days.	46	0	46	12	46
EG005	VX-150 - Dose Level 5	Participants received VX-150 250 mg qd for 2 days.	27	1	27	4	27

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Hypersensitivity	Immune system disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected46 at risk EG0010 affected42 at risk EG0020 affected44 at risk EG0030 affected45 at risk EG0040 affected46 at risk EG0051 affected27 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment		EG0000 affected46 at risk EG0010 affected42 at risk EG0020 affected44 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0005 affected46 at risk EG0017 affected42 at risk EG0029 affected44 at risk EG0038 affected45 at risk EG0048 affected46 at risk EG0052 affected27 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected46 at risk EG0014 affected42 at risk EG0025 affected44 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected46 at risk EG0012 affected42 at risk EG0023 affected44 at risk EG003

Group IDs	Statistical Method	P-Value	Non-Inferiority Type
OG000 OG001	Cochran-Mantel-Haenszel	0.3162	Superiority
OG000 OG002	Cochran-Mantel-Haenszel	0.4613	Superiority
OG000 OG003	Cochran-Mantel-Haenszel	0.4095	Superiority
OG000 OG004	Cochran-Mantel-Haenszel	0.1570	Superiority
OG000 OG005	Cochran-Mantel-Haenszel	0.9843	Superiority

Group IDs	Statistical Method	P-Value	Non-Inferiority Type
OG000 OG001	Cochran-Mantel-Haenszel	0.8714	Superiority
OG000 OG002	Cochran-Mantel-Haenszel	0.5815	Superiority
OG000 OG003	Cochran-Mantel-Haenszel	0.4308	Superiority
OG000 OG004	Cochran-Mantel-Haenszel	0.4434	Superiority
OG000 OG005	Cochran-Mantel-Haenszel	0.8550	Superiority

Group IDs	Statistical Method	P-Value	Non-Inferiority Type
OG000 OG001	Cochran-Mantel-Haenszel	0.6870	Superiority
OG000 OG002	Cochran-Mantel-Haenszel	0.1515	Superiority
OG000 OG003	Cochran-Mantel-Haenszel	0.6030	Superiority
OG000 OG004	Cochran-Mantel-Haenszel	0.1361	Superiority
OG000 OG005	Cochran-Mantel-Haenszel	0.5640	Superiority

Group IDs	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Regression, Cox	0.5405	Hazard Ratio (HR)	1.26	2-Sided	95	0.60	2.67	Superiority
OG000 OG002	Regression, Cox	0.9011	Hazard Ratio (HR)	1.05	2-Sided	95	0.49	2.27	Superiority
OG000 OG003	Regression, Cox	0.9127	Hazard Ratio (HR)	1.04	2-Sided	95	0.48	2.26	Superiority
OG000 OG004	Regression, Cox	0.5619	Hazard Ratio (HR)	1.24	2-Sided	95	0.60	2.56	Superiority
OG000 OG005	Regression, Cox	0.7090	Hazard Ratio (HR)	1.18	2-Sided	95	0.50	2.79	Superiority

Group IDs	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Regression, Cox	0.5141	Hazard Ratio (HR)	1.28	2-Sided	95	0.61	2.72	Superiority
OG000 OG002	Regression, Cox	0.9614	Hazard Ratio (HR)	0.98	2-Sided	95	0.45	2.12	Superiority
OG000 OG003	Regression, Cox	0.9756	Hazard Ratio (HR)	0.99	2-Sided	95	0.46	2.14	Superiority
OG000 OG004	Regression, Cox	0.5582	Hazard Ratio (HR)	1.24	2-Sided	95	0.60	2.57	Superiority
OG000 OG005	Regression, Cox	0.7543	Hazard Ratio (HR)	1.15	2-Sided	95	0.49	2.71	Superiority

Title

Denominators

Categories

VRT- 1207355: Day 1

- ParticipantsOG00041
- ParticipantsOG00140
- ParticipantsOG00243
- ParticipantsOG00343
- ParticipantsOG00424

Title	Measurements
	OG0004.97± 1.67 OG0013.27± 1.35 OG0021.71± 0.536 OG003

VRT- 1207355: Day 2

- ParticipantsOG00039
- ParticipantsOG00139
- ParticipantsOG00242
- ParticipantsOG00344

VRT- 1268114: Day 1

- ParticipantsOG00041
- ParticipantsOG00139
- ParticipantsOG00243
- ParticipantsOG00343

VRT- 1268114: Day 2

- ParticipantsOG00039
- ParticipantsOG00139
- ParticipantsOG00242
- ParticipantsOG00344

Title

Denominators

Categories

VRT- 1207355: Day 1

- ParticipantsOG00040
- ParticipantsOG00140
- ParticipantsOG00242
- ParticipantsOG00343
- ParticipantsOG00424

Title	Measurements
	OG00039.7± 13.4 OG00125.7± 11.0 OG00213.6± 4.60 OG003

VRT- 1207355: Day 2

- ParticipantsOG00039
- ParticipantsOG00139
- ParticipantsOG00242
- ParticipantsOG00344

VRT- 1268114: Day 1

- ParticipantsOG00040
- ParticipantsOG00139
- ParticipantsOG00242
- ParticipantsOG00343

VRT- 1268114: Day 2

- ParticipantsOG00039
- ParticipantsOG00139
- ParticipantsOG00242
- ParticipantsOG00344

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