Study of the Effect of Ivacaftor on Lung Clearance Index... | NCT01262352

Name	Class
Cystic Fibrosis Foundation	OTHER

Label	Type	Description	Intervention Names
Treatment Sequence 1	Experimental	Ivacaftor administered in Treatment Period 1 and placebo administered in Treatment Period 2.	Drug: Ivacaftor Drug: Placebo
Treatment Sequence 2	Experimental	Placebo administered in Treatment Period 1 and ivacaftor administered in Treatment Sequence 2.	Drug: Ivacaftor Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Ivacaftor	Drug	150 mg tablet, oral use, twice daily every 12 hours (q12h)	Treatment Sequence 1 Treatment Sequence 2

Measure	Description	Time Frame
Absolute Change From Baseline in Lung Clearance Index (LCI)	Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal SF6 concentration to 1/40th of the starting value.	Baseline through Day 29

Measure	Description	Time Frame
Absolute Change From Baseline in Percent Predicted FEV1	Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.	Baseline through Day 29
Change From Baseline in Sweat Chloride

Name	Affiliation	Role
Jane Davies	Royal Brompton Hospital and Imperial College	Principal Investigator
Felix Ratjen	The Hospital for Sick Children	Principal Investigator

PubMed Identifier	Type	Citation	Retractions
24461666	Derived	Davies J, Sheridan H, Bell N, Cunningham S, Davis SD, Elborn JS, Milla CE, Starner TD, Weiner DJ, Lee PS, Ratjen F. Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry: a randomised controlled trial. Lancet Respir Med. 2013 Oct;1(8):630-638. doi: 10.1016/S2213-2600(13)70182-6. Epub 2013 Sep 10.

ID	Title	Description
FG000	Ivacaftor Then Placebo	Ivacaftor administered in Treatment Period 1 and placebo administered in Treatment Period 2.
FG001	Placebo Then Ivacaftor	Placebo administered in Treatment Period 1 and ivacaftor administered in Treatment Period 2.

ID	Title	Description
BG000	Ivacaftor Then Placebo	Ivacaftor administered in Treatment Period 1 and placebo administered in Treatment Period 2.
BG001	Placebo Then Ivacaftor	Placebo administered in Treatment Period 1 and ivacaftor administered in Treatment Period 2.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG00110 BG00220

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0009 BG0017 BG00216
Between 18 and 65 years

Age Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00013.4± 7.12 BG00119.8± 13.35 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0006 BG0014 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

North America

Title	Measurements
	BG0006 BG0015 BG002

Height

Mean

Standard Deviation

centimeters

Title

Denominators

Categories

Title	Measurements
	BG000148.9± 19.54 BG001156.0± 17.92 BG002

Weight

Mean

Standard Deviation

kilograms

Title

Denominators

Categories

Title	Measurements
	BG00045.06± 20.018 BG00158.78± 30.576 BG002

Body Mass Index

Mean

Standard Deviation

kilograms per square meter

Title

Denominators

Categories

Title	Measurements
	BG00019.36± 3.707 BG00122.66± 6.964 BG002

Lung Clearance Index (LCI)

Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal SF6 concentration to 1/40th of the starting value.

Mean

Standard Deviation

ratio

Title

Denominators

Categories

Title	Measurements
	BG0009.17± 1.657 BG001

Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)

Mean

Standard Deviation

percentage

Title

Denominators

Categories

Title	Measurements
	BG000101.83± 11.587 BG00192.58± 7.427 BG002

Sweat Chloride

Mean

Standard Deviation

millimoles per liter

Title

Denominators

Categories

Title	Measurements
	BG00097.10± 7.400 BG00186.17± 19.219 BG002

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

Absolute Change From Baseline in Lung Clearance Index (LCI)

All randomized subjects who received at least 1 dose of study drug (placebo or ivacaftor) and had available assessments during the time frame.

Posted

Least Squares Mean

Standard Error

ratio

Baseline through Day 29

ID	Title	Description
OG000	Placebo	Oral tablet every 12 hours (q12h) for up to 28 days.
OG001	Ivacaftor	Oral tablet of 150 mg of ivacaftor q12h for up to 28 days.

Units	Counts
Participants	OG00018 OG00117

Title

Denominators

Categories

Title	Measurements
	OG0000.77± 0.291 OG001-1.30± 0.303

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The primary analysis for the primary efficacy variable was based on a mixed effect model. The model included the absolute change from the baseline in each period as the dependent variable, sequence, treatment, and period as fixed effects, study baseline LCI as the covariate, and subject nested within sequence as the random effect.	Mixed Models Analysis		0.0004		Mean Difference (Final Values)	-2.069			2-Sided	95	-2.98	-1.15				No	Superiority or Other

Secondary

Absolute Change From Baseline in Percent Predicted FEV1

Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.

All randomized subjects who received at least 1 dose of study drug (placebo or ivacaftor) and had available assessments during the time frame.

Posted

Least Squares Mean

Standard Error

percent

Baseline through Day 29

ID	Title	Description
OG000	Placebo	Oral tablet every 12 hours (q12h) for up to 28 days.
OG001	Ivacaftor	Oral tablet of 150 mg of ivacaftor q12h for up to 28 days.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Sweat Chloride

The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.

All randomized subjects who received at least 1 dose of study drug (placebo or ivacaftor) and had available assessments during the time frame.

Posted

Least Squares Mean

Standard Error

millimoles per liter

Baseline through Day 29

ID	Title	Description
OG000	Placebo	Oral tablet every 12 hours (q12h) for up to 28 days.
OG001	Ivacaftor	Oral tablet of 150 mg of ivacaftor q12h for up to 28 days.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in CF Questionnaire-Revised (CFQ-R) Score (Respiratory Domain Score, Pooled)

The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID). The primary analytical focus was the respiratory health domain, which was analyzed by combining all self-response questionnaire versions from different age groups (e.g., Adult/Adolescent and Child versions).

All randomized subjects who received at least 1 dose of study drug (placebo or ivacaftor) and had available assessments during the time frame.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline through Day 29

ID	Title	Description
OG000	Placebo	Oral tablet every 12 hours (q12h) for up to 28 days.
OG001	Ivacaftor	Oral tablet of 150 mg of ivacaftor q12h for up to 28 days.

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vomiting	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0004 events4 affected19 at risk EG0011 events1 affected18 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected19 at risk EG0010 events0 affected18 at risk
Constipation	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0012 events1 affected18 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Abdominal tenderness	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Flatulence	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Nausea	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG00010 events7 affected19 at risk EG0015 events5 affected18 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected19 at risk EG0011 events1 affected18 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected19 at risk EG0010 events0 affected18 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected18 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected18 at risk
Nasal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Nasal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0002 events1 affected19 at risk EG0010 events0 affected18 at risk
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Headache	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0014 events4 affected18 at risk
Dizziness	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0013 events2 affected18 at risk
Hypoaesthesia	Nervous system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Pyrexia	General disorders	MedDRA (12.0)	Systematic Assessment	EG0003 events3 affected19 at risk EG0011 events1 affected18 at risk
Fatigue	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected18 at risk
Application site papules	General disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0002 events2 affected19 at risk EG0010 events0 affected18 at risk
Gastrointestinal viral infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Mycobacterium abscessus infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Oral candidiasis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Pneumococcal infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Sinusitis	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Staphylococcal infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Vulvovaginal mycotic infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0011 events1 affected18 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Blister	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Swelling face	Skin and subcutaneous tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Bite	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Joint sprain	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Medical device complication	Injury, poisoning and procedural complications	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Bacteria sputum identified	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Bacterial culture positive	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Lymph node palpable	Investigations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Prothrombin time prolonged	Investigations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Seasonal allergy	Immune system disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0012 events2 affected18 at risk
Ear pain	Ear and labyrinth disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Glycosuria	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Haematuria	Renal and urinary disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Nipple disorder	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Nipple pain	Reproductive system and breast disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Cystic fibrosis lung	Congenital, familial and genetic disorders	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Stanford	California		United States

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	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Oral tablet every 12 hours (q12h) for up to 28 days.			1	19	15	19
EG001	Ivacaftor	Oral tablet of 150 mg of ivacaftor q12h for up to 28 days.			2	18	13	18

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchopulmonary aspergillosis allergic	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0001 events1 affected19 at risk EG0010 events0 affected18 at risk
Pseudomonas infection	Infections and infestations	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Cystic fibrosis lung	Congenital, familial and genetic disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk
Distal ileal obstruction syndrome	Gastrointestinal disorders	MedDRA (12.0)	Systematic Assessment	EG0000 events0 affected19 at risk EG0011 events1 affected18 at risk