Trial Outcomes & Findings for Study of VX-809 in Cystic Fibrosis Subjects With the ∆F508-CFTR Gene Mutation (NCT NCT00865904)

NCT ID: NCT00865904

Last Updated: 2015-08-28

Results Overview

AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. Serious adverse event (SAE) (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 93 participants
• Primary outcome timeframe: Up to 14 days after last dose (last dose = Day 28)
• Results posted on: 2015-08-28

Participant Flow

Participant milestones

Measure	Placebo Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg VX-809, 25 milligram (mg) capsule orally once daily for 28 days.	VX-809, 50 mg VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg VX-809, 200 mg capsule orally once daily for 28 days.
Overall Study STARTED	19	18	18	18	20
Overall Study COMPLETED	17	18	18	17	19
Overall Study NOT COMPLETED	2	0	0	1	1

Reasons for withdrawal

Measure	Placebo Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg VX-809, 25 milligram (mg) capsule orally once daily for 28 days.	VX-809, 50 mg VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg VX-809, 200 mg capsule orally once daily for 28 days.
Overall Study Randomized but not Treated	2	0	0	1	1

Baseline Characteristics

Study of VX-809 in Cystic Fibrosis Subjects With the ∆F508-CFTR Gene Mutation

Baseline characteristics by cohort

Measure	Placebo n=17 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=18 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=18 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=17 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=19 Participants VX-809, 200 mg capsule orally once daily for 28 days.	Total n=89 Participants Total of all reporting groups
Age, Continuous	31.5 years STANDARD_DEVIATION 9.35 • n=93 Participants	27.7 years STANDARD_DEVIATION 8.98 • n=4 Participants	27.1 years STANDARD_DEVIATION 8.20 • n=27 Participants	30.1 years STANDARD_DEVIATION 11.55 • n=483 Participants	26.7 years STANDARD_DEVIATION 6.82 • n=36 Participants	28.6 years STANDARD_DEVIATION 9.1 • n=10 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	9 Participants n=4 Participants	9 Participants n=27 Participants	5 Participants n=483 Participants	7 Participants n=36 Participants	36 Participants n=10 Participants
Sex: Female, Male Male	11 Participants n=93 Participants	9 Participants n=4 Participants	9 Participants n=27 Participants	12 Participants n=483 Participants	12 Participants n=36 Participants	53 Participants n=10 Participants

PRIMARY outcome

Timeframe: Up to 14 days after last dose (last dose = Day 28)

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

AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. Serious adverse event (SAE) (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent.

Outcome measures

Measure	Placebo n=17 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=18 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=18 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=17 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=19 Participants VX-809, 200 mg capsule orally once daily for 28 days.
Safety and Tolerability Based on Adverse Events (AEs) Participants With Any AE	17 participants	16 participants	15 participants	16 participants	18 participants
Safety and Tolerability Based on Adverse Events (AEs) Participants With SAE	1 participants	5 participants	1 participants	0 participants	3 participants

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug. Number of participants analyzed signifies participants evaluable for this outcome.

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Outcome measures

Measure	Placebo n=17 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=17 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=17 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=16 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=18 Participants VX-809, 200 mg capsule orally once daily for 28 days.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28	0.029 liters Interval -0.0823 to 0.1398	-0.049 liters Interval -0.1578 to 0.0588	-0.031 liters Interval -0.1401 to 0.0787	0.015 liters Interval -0.0972 to 0.1263	-0.009 liters Interval -0.1146 to 0.097

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method.

Outcome measures

Measure	Placebo n=17 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=17 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=17 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=16 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=18 Participants VX-809, 200 mg capsule orally once daily for 28 days.
Change From Baseline in Percent Predicted FEV1 at Day 28	0.285 Percent predicted of FEV1 Interval -2.8268 to 3.3973	-1.637 Percent predicted of FEV1 Interval -4.6836 to 1.4089	-0.375 Percent predicted of FEV1 Interval -3.454 to 2.7046	0.168 Percent predicted of FEV1 Interval -2.9653 to 3.3011	-0.165 Percent predicted of FEV1 Interval -3.1346 to 2.8044

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.

FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.

Outcome measures

Measure	Placebo n=17 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=17 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=17 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=16 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=18 Participants VX-809, 200 mg capsule orally once daily for 28 days.
Change From Baseline in Forced Vital Capacity (FVC) at Day 28	0.085 liters Standard Deviation 0.2857	-0.055 liters Standard Deviation 0.2331	-0.020 liters Standard Deviation 0.3494	-0.004 liters Standard Deviation 0.1916	-0.023 liters Standard Deviation 0.3668

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.

FEF25-75 is total volume of air exhaled from the lungs over the middle half of the FVC test, expressed as liters per second (L/sec).

Outcome measures

Measure	Placebo n=17 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=17 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=17 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=16 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=18 Participants VX-809, 200 mg capsule orally once daily for 28 days.
Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28	-0.030 liters per second (L/sec) Standard Deviation 0.1730	-0.011 liters per second (L/sec) Standard Deviation 0.3231	-0.029 liters per second (L/sec) Standard Deviation 0.4373	0.045 liters per second (L/sec) Standard Deviation 0.2702	-0.052 liters per second (L/sec) Standard Deviation 0.3558

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.

Sweat samples were collected using an approved Macroduct (Wescor) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride.

Outcome measures

Measure	Placebo n=16 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=16 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=16 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=15 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=16 Participants VX-809, 200 mg capsule orally once daily for 28 days.
Change From Baseline in Sweat Chloride at Day 28	0.84 millimole per liter (mmol/L) Interval -3.493 to 5.166	0.93 millimole per liter (mmol/L) Interval -3.308 to 5.173	-3.77 millimole per liter (mmol/L) Interval -7.966 to 0.416	-5.29 millimole per liter (mmol/L) Interval -9.618 to -0.963	-7.38 millimole per liter (mmol/L) Interval -11.59 to -3.166

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.

Nasal potential difference (NPD) provides a direct and sensitive evaluation of sodium and chloride transport in secretory epithelial cells via assessment of transepithelial bioelectric properties. NPD under conditions of zero chloride concentration perfusion solution in the presence of isoproterenol is reported.

NPDs were performed according to Cystic Fibrosis Foundation Therapeutics Development Network (CFFT TDN) Standard Operating Procedure (SOP) 528.00 "Standardization of Measurement of Nasal Membrane Transepithelial Potential Difference (NPD) - electronic data capture (EDC) and Perfusion or Perfusion-Free Probe".

Outcome measures

Measure	Placebo n=12 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=16 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=13 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=11 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=12 Participants VX-809, 200 mg capsule orally once daily for 28 days.
Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28	-1.017 millivolts (mV) Interval -3.2979 to 1.2637	0.832 millivolts (mV) Interval -1.1302 to 2.7943	0.142 millivolts (mV) Interval -2.0369 to 2.3208	1.382 millivolts (mV) Interval -0.9853 to 3.7491	1.583 millivolts (mV) Interval -0.6952 to 3.8612

SECONDARY outcome

Timeframe: Baseline, Day 28

Population: FAS. Number of participants analyzed signifies participants evaluable for this outcome.

The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. CFQ-R domains include: Body, Digestion, Eat, Emotion, Health Perceptions, Physical, Respiratory, Role, Social, Treatment Burden, Vitality, and Weight. Individual domain score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

Outcome measures

Measure	Placebo n=17 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=17 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=17 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=16 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=18 Participants VX-809, 200 mg capsule orally once daily for 28 days.
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Body	-1.341 units on a scale Interval -6.4183 to 3.737	-0.206 units on a scale Interval -5.2276 to 4.8151	-1.626 units on a scale Interval -6.6796 to 3.4276	2.611 units on a scale Interval -2.5525 to 7.7746	0.058 units on a scale Interval -4.8954 to 5.0123
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Digestion	4.620 units on a scale Interval -0.253 to 9.4935	2.284 units on a scale Interval -2.4928 to 7.0605	-0.719 units on a scale Interval -5.5599 to 4.1216	0.251 units on a scale Interval -4.6794 to 5.181	2.578 units on a scale Interval -2.1027 to 7.258
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Eat	2.110 units on a scale Interval -3.9925 to 8.2128	-3.662 units on a scale Interval -9.6704 to 2.3463	-7.269 units on a scale Interval -13.3216 to -1.2161	3.242 units on a scale Interval -3.0242 to 9.5087	-2.576 units on a scale Interval -8.4313 to 3.2793
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Emotion	4.859 units on a scale Interval -0.42 to 10.1372	-3.222 units on a scale Interval -8.4312 to 1.9866	-1.358 units on a scale Interval -6.5817 to 3.8666	3.489 units on a scale Interval -1.9312 to 8.9087	-2.624 units on a scale Interval -7.7058 to 2.4585
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Health Perceptions	5.034 units on a scale Interval -1.6041 to 11.6713	-2.839 units on a scale Interval -9.2912 to 3.6131	-6.967 units on a scale Interval -13.4203 to -0.5137	-0.435 units on a scale Interval -7.0778 to 6.2074	-1.896 units on a scale Interval -8.3524 to 4.5604
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Physical	1.225 units on a scale Interval -5.3271 to 7.7764	-5.968 units on a scale Interval -12.3586 to 0.4217	-7.384 units on a scale Interval -13.8167 to -0.9508	-3.464 units on a scale Interval -10.0613 to 3.1335	-0.976 units on a scale Interval -7.2596 to 5.3067
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Respiratory	4.534 units on a scale Interval -1.6158 to 10.6842	-5.223 units on a scale Interval -11.2414 to 0.7956	-6.324 units on a scale Interval -12.3453 to -0.3026	-1.290 units on a scale Interval -7.5407 to 4.9598	2.215 units on a scale Interval -3.661 to 8.0901
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Role	2.210 units on a scale Interval -3.2279 to 7.6481	-5.941 units on a scale Interval -11.3247 to -0.5577	-4.599 units on a scale Interval -9.9912 to 0.7925	1.097 units on a scale Interval -4.4579 to 6.651	-6.533 units on a scale Interval -11.7858 to -1.2803
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Social	-0.554 units on a scale Interval -4.8235 to 3.7152	-0.001 units on a scale Interval -4.2221 to 4.22	-1.013 units on a scale Interval -5.2372 to 3.2122	0.469 units on a scale Interval -3.8898 to 4.8273	-2.640 units on a scale Interval -6.7802 to 1.5008
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Treatment Burden	2.463 units on a scale Interval -3.1916 to 8.1169	4.185 units on a scale Interval -1.422 to 9.7914	-5.962 units on a scale Interval -11.5712 to -0.353	1.421 units on a scale Interval -4.3528 to 7.1954	-0.676 units on a scale Interval -6.1363 to 4.7843
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Vitality	-2.178 units on a scale Interval -8.8193 to 4.4629	-4.645 units on a scale Interval -11.1048 to 1.8139	-7.227 units on a scale Interval -13.6961 to -0.7589	-1.516 units on a scale Interval -8.18 to 5.1472	0.730 units on a scale Interval -5.5932 to 7.0522
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 Weight	0.304 units on a scale Interval -9.446 to 10.0543	5.410 units on a scale Interval -4.2393 to 15.06	2.175 units on a scale Interval -7.55 to 11.8997	8.827 units on a scale Interval -1.1524 to 18.8063	-4.186 units on a scale Interval -13.5956 to 5.2233

SECONDARY outcome

Timeframe: Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, 24, and 30-60 hours post dose)

Population: FAS. Here, n = participants evaluable for specified category for each arm, respectively.

Only participants who received VX-809 were analyzed for this outcome measure.

Outcome measures

Measure	Placebo n=18 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=18 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=17 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=19 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg VX-809, 200 mg capsule orally once daily for 28 days.
Maximum Plasma Concentration (Cmax) of VX-809 Day 1 (n= 18, 18, 17, 19)	760 nanogram per milliliter (ng/mL) Standard Deviation 280	1850 nanogram per milliliter (ng/mL) Standard Deviation 697	2930 nanogram per milliliter (ng/mL) Standard Deviation 916	6410 nanogram per milliliter (ng/mL) Standard Deviation 2550	—
Maximum Plasma Concentration (Cmax) of VX-809 Day 28 (n= 17, 17, 16, 18)	1100 nanogram per milliliter (ng/mL) Standard Deviation 443	2660 nanogram per milliliter (ng/mL) Standard Deviation 1010	4620 nanogram per milliliter (ng/mL) Standard Deviation 1840	10300 nanogram per milliliter (ng/mL) Standard Deviation 4490	—

SECONDARY outcome

Timeframe: Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post dose)

Population: FAS. Here, n = participants evaluable for specified category for each arm, respectively.

Only participants who received VX-809 were analyzed for this outcome measure.

Outcome measures

Measure	Placebo n=18 Participants Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=18 Participants VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=17 Participants VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=19 Participants VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg VX-809, 200 mg capsule orally once daily for 28 days.
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 Day 1 (n= 18, 18, 17, 19)	7190 hour*nanogram per milliliter (hr*ng/mL) Standard Deviation 2190	16600 hour*nanogram per milliliter (hr*ng/mL) Standard Deviation 6290	29000 hour*nanogram per milliliter (hr*ng/mL) Standard Deviation 11400	59500 hour*nanogram per milliliter (hr*ng/mL) Standard Deviation 26400	—
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 Day 28 (n= 17, 17, 16, 18)	12900 hour*nanogram per milliliter (hr*ng/mL) Standard Deviation 4920	28800 hour*nanogram per milliliter (hr*ng/mL) Standard Deviation 13100	54100 hour*nanogram per milliliter (hr*ng/mL) Standard Deviation 31600	119000 hour*nanogram per milliliter (hr*ng/mL) Standard Deviation 73700	—

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

VX-809, 25 mg

Serious events: 5 serious events

Other events: 16 other events

Deaths: 0 deaths

VX-809, 50 mg

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

VX-809, 100 mg

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

VX-809, 200 mg

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=17 participants at risk Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=18 participants at risk VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=18 participants at risk VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=17 participants at risk VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=19 participants at risk VX-809, 200 mg capsule orally once daily for 28 days.
Congenital, familial and genetic disorders Cystic fibrosis lung	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	22.2% 4/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	15.8% 3/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)

Other adverse events

Measure	Placebo n=17 participants at risk Placebo matched to VX-809 capsule orally once daily for 28 days.	VX-809, 25 mg n=18 participants at risk VX-809, 25 mg capsule orally once daily for 28 days.	VX-809, 50 mg n=18 participants at risk VX-809, 50 mg capsule orally once daily for 28 days.	VX-809, 100 mg n=17 participants at risk VX-809, 100 mg capsule orally once daily for 28 days.	VX-809, 200 mg n=19 participants at risk VX-809, 200 mg capsule orally once daily for 28 days.
Respiratory, thoracic and mediastinal disorders Cough	41.2% 7/17 • Up to 14 days after last dose (last dose = Day 28)	55.6% 10/18 • Up to 14 days after last dose (last dose = Day 28)	33.3% 6/18 • Up to 14 days after last dose (last dose = Day 28)	41.2% 7/17 • Up to 14 days after last dose (last dose = Day 28)	52.6% 10/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	27.8% 5/18 • Up to 14 days after last dose (last dose = Day 28)	16.7% 3/18 • Up to 14 days after last dose (last dose = Day 28)	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	21.1% 4/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Productive cough	17.6% 3/17 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	23.5% 4/17 • Up to 14 days after last dose (last dose = Day 28)	31.6% 6/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Rales	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	33.3% 6/18 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	17.6% 3/17 • Up to 14 days after last dose (last dose = Day 28)	15.8% 3/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Nasal congestion	17.6% 3/17 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	10.5% 2/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Wheezing	17.6% 3/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	22.2% 4/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	17.6% 3/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	16.7% 3/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	10.5% 2/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Pleuritic pain	17.6% 3/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Respiration abnormal	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	21.1% 4/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Sinus congestion	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Haemoptysis	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	10.5% 2/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	17.6% 3/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Epistaxis	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	10.5% 2/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Nasal oedema	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Increased viscosity of bronchial secretion	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Lung hyperinflation	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Nasal turbinate abnormality	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Postnasal drip	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Rhonchi	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Nasal mucosal disorder	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Nasal ulcer	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Painful respiration	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Sputum discoloured	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Tonsillar inflammation	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Diarrhoea	17.6% 3/17 • Up to 14 days after last dose (last dose = Day 28)	16.7% 3/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Abdominal pain	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	16.7% 3/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Constipation	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Abdominal pain upper	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	10.5% 2/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Nausea	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	16.7% 3/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Post-tussive vomiting	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Flatulence	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Abdominal pain lower	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Aphthous stomatitis	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Dyspepsia	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Gastrointestinal sounds abnormal	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Abdominal discomfort	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Abdominal distension	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Abnormal faeces	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Dry mouth	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Frequent bowel movements	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Gingival pain	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Infrequent bowel movements	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Gastrointestinal disorders Vomiting	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Fatigue	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	16.7% 3/18 • Up to 14 days after last dose (last dose = Day 28)	16.7% 3/18 • Up to 14 days after last dose (last dose = Day 28)	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	15.8% 3/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Pyrexia	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	26.3% 5/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Pain	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Chest discomfort	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Catheter site haematoma	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Catheter site rash	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Chest pain	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Chills	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Hunger	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Irritability	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Nodule	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
General disorders Oedema peripheral	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Breath sounds abnormal	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Forced expiratory volume decreased	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Pulmonary function test decreased	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations C-reactive protein increased	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Prothrombin time prolonged	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Sputum abnormal	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Blood glucose increased	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Neutrophil count increased	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations White blood cell count increased	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Activated partial thromboplastin time prolonged	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Alanine aminotransferase increased	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Blood urine present	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Electrocardiogram QT prolonged	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Glucose urine	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Protein urine present	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Urine leukocyte esterase positive	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Weight decreased	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Nervous system disorders Headache	17.6% 3/17 • Up to 14 days after last dose (last dose = Day 28)	22.2% 4/18 • Up to 14 days after last dose (last dose = Day 28)	27.8% 5/18 • Up to 14 days after last dose (last dose = Day 28)	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	26.3% 5/19 • Up to 14 days after last dose (last dose = Day 28)
Nervous system disorders Dizziness	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Nervous system disorders Tension headache	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Nervous system disorders Hypogeusia	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Nervous system disorders Migraine	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Investigations Sinus headache	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Nervous system disorders Somnolence	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Myalgia	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	16.7% 3/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Arthralgia	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Clubbing	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Flank pain	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Joint effusion	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Medial tibial stress syndrome	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Musculoskeletal and connective tissue disorders Tendonitis	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Infections and infestations Upper respiratory tract infection	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	11.1% 2/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	17.6% 3/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Infections and infestations Nasopharyngitis	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	10.5% 2/19 • Up to 14 days after last dose (last dose = Day 28)
Infections and infestations Rhinitis	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Infections and infestations Influenza	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Infections and infestations Gastroenteritis	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Infections and infestations Oral candidiasis	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Infections and infestations Pharyngitis streptococcal	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Infections and infestations Sinusitis	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Infections and infestations Urinary tract infection	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Infections and infestations Vulvovaginal mycotic infection	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Skin and subcutaneous tissue disorders Acne	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Skin and subcutaneous tissue disorders Erythema	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Skin and subcutaneous tissue disorders Rash	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Skin and subcutaneous tissue disorders Blister	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Congenital, familial and genetic disorders Cystic fibrosis lung	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	11.8% 2/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Congenital, familial and genetic disorders Cystic fibrosis related diabetes	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Injury, poisoning and procedural complications Contusion	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Injury, poisoning and procedural complications Post procedural haemorrhage	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Injury, poisoning and procedural complications Epicondylitis	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Injury, poisoning and procedural complications Muscle strain	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Injury, poisoning and procedural complications Sunburn	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Ear and labyrinth disorders Ear pain	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Ear and labyrinth disorders Tympanic membrane hyperaemia	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Ear and labyrinth disorders Middle ear effusion	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Ear and labyrinth disorders Motion sickness	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Ear and labyrinth disorders Vertigo	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Metabolism and nutrition disorders Hypoglycaemia	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Metabolism and nutrition disorders Gout	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Metabolism and nutrition disorders Polydipsia	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Psychiatric disorders Anxiety	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Psychiatric disorders Agitation	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Psychiatric disorders Depression	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Renal and urinary disorders Haematuria	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Renal and urinary disorders Polyuria	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Renal and urinary disorders Proteinuria	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Vascular disorders Haematoma	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Vascular disorders Hypertension	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.9% 1/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)
Cardiac disorders Palpitations	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	5.3% 1/19 • Up to 14 days after last dose (last dose = Day 28)
Eye disorders Conjunctival hyperaemia	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/18 • Up to 14 days after last dose (last dose = Day 28)	5.6% 1/18 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/17 • Up to 14 days after last dose (last dose = Day 28)	0.00% 0/19 • Up to 14 days after last dose (last dose = Day 28)

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: 617-341-6777

Email: medicalinfo@vrtx.com

Results disclosure agreements

• Principal investigator is a sponsor employee PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
• Publication restrictions are in place

Restriction type: OTHER