A Study to Evaluate the Safety and Efficacy of VX-121 Com... | NCT03912233

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part 1: Placebo	Placebo Comparator	Participants received placebo matched to VX-121/TEZ/VX-561 triple combination (TC) for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.	Drug: Placebo
Part 1: VX-121/TEZ/VX-561 TC - Low Dose	Experimental	Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period	Drug: VX-121 Drug: TEZ Drug: VX-561
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	Experimental	Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.	Drug: VX-121 Drug: TEZ Drug: VX-561
Part 1: VX-121/TEZ/VX-561 TC - High Dose	Experimental	Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.	Drug: VX-121 Drug: TEZ Drug: VX-561
Part 2: TEZ/IVA

Interventions

Name	Type	Description	Arm Group Labels	Other Names
VX-121	Drug	Tablets for oral administration.	Part 1: VX-121/TEZ/VX-561 TC - High Dose Part 1: VX-121/TEZ/VX-561 TC - Low Dose Part 1: VX-121/TEZ/VX-561 TC - Medium Dose

Measure	Description	Time Frame
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	From Baseline Through Day 29

Measure	Description	Time Frame
Absolute Change in Sweat Chloride (SwCl) Concentrations	Sweat samples were collected using an approved collection device.	From Baseline Through Day 29
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

Facility	Status	City	State	ZIP	Country	Contacts
Keck Medical Center of University of Southern California		Los Angeles	California	90033	United States

PubMed Identifier	Type	Citation	Retractions
36842446	Derived	Uluer AZ, MacGregor G, Azevedo P, Indihar V, Keating C, Mall MA, McKone EF, Ramsey BW, Rowe SM, Rubenstein RC, Taylor-Cousar JL, Tullis E, Yonker LM, Chu C, Lam AP, Nair N, Sosnay PR, Tian S, Van Goor F, Viswanathan L, Waltz D, Wang LT, Xi Y, Billings J, Horsley A; VX18-121-101; VX18-561-101 Study Groups. Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials. Lancet Respir Med. 2023 Jun;11(6):550-562. doi: 10.1016/S2213-2600(22)00504-5. Epub 2023 Feb 23.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part 1: Placebo	Participants received placebo matched to VX-121/tezacaftor (TEZ)/VX-561 triple combination (TC) for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.
FG001	Part 1: VX-121/TEZ/VX-561 TC - Low Dose

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 9, 2019	Aug 18, 2021

Arm/Group Information

ID	Title	Description
BG000	Part 1: Placebo	Participants received placebo matched to VX-121/TEZ/VX-561 TC for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.
BG001	Part 1: VX-121/TEZ/VX-561 TC - Low Dose	Participants received VX-121 5 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
BG002	Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
BG003	Part 1: VX-121/TEZ/VX-561 TC - High Dose	Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
BG004	Part 2: TEZ/IVA	Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.
BG005	Part 2: VX-121/TEZ/VX-561 TC - High Dose	Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.
BG006	Total	Total of all reporting groups

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

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 in the treatment period.

Posted

Number

participants

From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)

ID	Title	Description
OG000	Part 1: Placebo	Participants received placebo matched to VX-121/TEZ/VX-561 TC for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.
OG001	Part 1: VX-121/TEZ/VX-561 TC - Low Dose	Participants received VX-121 5 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
OG002	Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
OG003	Part 1: VX-121/TEZ/VX-561 TC - High Dose	Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
OG004	Part 2: TEZ/IVA	Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.
OG005	Part 2: VX-121/TEZ/VX-561 TC - High Dose	Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.

Units	Counts
Participants	OG00010 OG0019 OG00219 OG003

Title

Denominators

Categories

Participants With AEs

Title	Measurements
	OG0009 OG0018 OG00216 OG003

Primary

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

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

Full analysis set (FAS) included all randomized participants who carry the intended cystic fibrosis transmembrane conductance regulator gene (CFTR) allele mutation(s) and received at least 1 dose of study drug in the treatment period.

Posted

Least Squares Mean

95% Confidence Interval

percentage points

From Baseline Through Day 29

ID	Title	Description
OG000	Part 1: Placebo	Participants received placebo matched to VX-121/TEZ/VX-561 TC for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.
OG001	Part 1: VX-121/TEZ/VX-561 TC - Low Dose	Participants received VX-121 5 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
OG002	Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.

Secondary

Absolute Change in Sweat Chloride (SwCl) Concentrations

Sweat samples were collected using an approved collection device.

FAS.

Posted

Least Squares Mean

95% Confidence Interval

millimole per liter (mmol/L)

From Baseline Through Day 29

ID	Title	Description
OG000	Part 1: Placebo	Participants received placebo matched to VX-121/TEZ/VX-561 TC for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.
OG001	Part 1: VX-121/TEZ/VX-561 TC - Low Dose	Participants received VX-121 5 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
OG002	Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
OG003	Part 1: VX-121/TEZ/VX-561 TC - High Dose

Secondary

Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

FAS.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

From Baseline at Day 29

ID	Title	Description
OG000	Part 1: Placebo	Participants received placebo matched to VX-121/TEZ/VX-561 TC for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.
OG001	Part 1: VX-121/TEZ/VX-561 TC - Low Dose	Participants received VX-121 5 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
OG002	Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.

Secondary

Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561)

Pharmacokinetic (PK) set included all participants who received at least 1 dose study drug in the treatment period and for whom the PK data are considered sufficient and interpretable. Participants who received VX-121/TEZ/VX-561 TC in Parts 1 or 2 were to be analyzed for Ctrough. Overall participants in Part 1 were assessed for Ctrough, therefore data are reported in single Part 1: TC combined arm. The "number analyzed" signifies participants who were evaluable at specified time point.

Posted

Mean

Standard Deviation

nanogram per milliliter (ng/mL)

Pre-dose at Day 15 and Day 29

ID	Title	Description
OG000	Part 1: VX-121/TEZ/VX-561 TC - Combined	Participants who either received VX-121 5 mg, 10 mg or 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
OG001	Part 2: VX-121/TEZ/VX-561 TC - High Dose	Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: Placebo	Participants received placebo matched to VX-121/TEZ/VX-561 TC for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.	10	2	10	9	10
EG001	Part 1: VX-121/TEZ/VX-561 TC - Low Dose	Participants received VX-121 5 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.	9	1	9	8	9
EG002	Part 1: VX-121/TEZ/VX-561 TC - Medium Dose	Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.	19	1	19	16	19
EG003	Part 1: VX-121/TEZ/VX-561 TC - High Dose	Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.	20	0	20	20	20
EG004	Part 2: TEZ/IVA	Following run-in period with TEZ 100 mg/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period.	10	0	10	8	10
EG005	Part 2: VX-121/TEZ/VX-561 TC - High Dose	Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.	18	0	18	16	18

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG0030 affected20 at risk EG0040 affected10 at risk EG0050 affected18 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Palpitations	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Swelling of eyelid	Eye disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0021 affected19 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0024 affected19 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Frequent bowel movements	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Post-tussive vomiting	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Salivary hypersecretion	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Asthenia	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Chest pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Chills	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Fatigue	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected9 at risk EG0025 affected19 at risk EG003
Feeling abnormal	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Influenza like illness	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Malaise	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Oedema peripheral	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Pain	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Pyrexia	General disorders	MedDRA 22.1	Systematic Assessment	EG0002 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Bronchopulmonary aspergillosis allergic	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0004 affected10 at risk EG0013 affected9 at risk EG0020 affected19 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0012 affected9 at risk EG0022 affected19 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Rhinitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Sinusitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Tooth infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Viral rash	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0023 affected19 at risk EG003
Vulvovaginal mycotic infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Activated partial thromboplastin time prolonged	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Blood bilirubin unconjugated increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0023 affected19 at risk EG003
Blood glucose increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Blood potassium increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Blood pressure diastolic increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Blood pressure increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Blood sodium decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Crystal urine present	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Eosinophil count increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Forced expiratory volume decreased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Glucose urine present	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
International normalised ratio increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Weight increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
White blood cell count increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0022 affected19 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Polydipsia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Tendon pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Dizziness	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0012 affected9 at risk EG0024 affected19 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Abnormal dreams	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Mood swings	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Panic attack	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Somnambulism	Psychiatric disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0005 affected10 at risk EG0014 affected9 at risk EG0025 affected19 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected9 at risk EG0022 affected19 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Lower respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0021 affected19 at risk EG003
Nasal obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0012 affected9 at risk EG0023 affected19 at risk EG003
Painful respiration	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Paranasal sinus hypersecretion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected10 at risk EG0010 affected9 at risk EG0022 affected19 at risk EG003
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Respiration abnormal	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0021 affected19 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0022 affected19 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0021 affected19 at risk EG003
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected10 at risk EG0016 affected9 at risk EG0023 affected19 at risk EG003
Throat clearing	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003
Exfoliative rash	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected10 at risk EG0011 affected9 at risk EG0020 affected19 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0020 affected19 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected9 at risk EG0021 affected19 at risk EG003

ID	Term
D010182	Pancreatic Diseases
D004066	Digestive System Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases

ID	Term
C000625213	tezacaftor
C000654124	tezacaftor, ivacaftor drug combination
C545203	ivacaftor