Safety Study of Ivacaftor in Subjects With Cystic Fibrosis
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study of VX-770 to Evaluate Safety, Pharmacokinetics, and Biomarkers of CFTR Activity in Cystic Fibrosis (CF) Subjects With Genotype G551D
1 other identifier
interventional
39
3 countries
15
Brief Summary
The purpose of this study was to evaluate the safety and tolerability of ivacaftor in patients with cystic fibrosis (CF) who were aged 18 years or older and have a G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent and selective CFTR potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators are pharmacological agents that increase the chloride ion transport properties of the channel in the presence of cyclic AMP-dependent protein kinase A (PKA) activation.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started May 2007
Shorter than P25 for phase_2
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 5, 2007
CompletedFirst Posted
Study publicly available on registry
April 9, 2007
CompletedStudy Start
First participant enrolled
May 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2008
CompletedResults Posted
Study results publicly available
October 5, 2012
CompletedOctober 5, 2012
October 1, 2012
1.3 years
April 5, 2007
February 27, 2012
October 3, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Subjects With Adverse Events (Combined Part 1 and Part 2)
Adverse event data were collected up to the follow-up visit (5 to 9 days after last dose of study drug). Serious adverse events that were ongoing at the follow-up visit were followed until the event resolved, returned to baseline, or was determined to be a stable or chronic condition.
Baseline to Follow-up
Number of Adverse Events (Combined Part 1 and Part 2)
Adverse event data were collected up to the follow-up visit (5 to 9 days after last dose of study drug). Serious adverse events that were ongoing at the follow-up visit were followed until the event resolved, returned to baseline, or was determined to be a stable or chronic condition.
Baseline to Follow-up
Secondary Outcomes (4)
Change From Baseline in Nasal Potential Difference (Combined Part 1 and Part 2)
14 days and 28 days
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second [FEV1] (Combined Part 1 and Part 2)
14 days and 28 days
Change From Baseline in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score (Part 2 Only)(Respiratory Domain Score)
14 days and 28 days
Change From Baseline in Maximum Sweat Chloride Concentration (Combined Part 1 and Part 2)
14 days and 28 days
Study Arms (4)
Ivacaftor Group A
EXPERIMENTALSubjects in Part 1 who first received 25 mg or 75 mg of ivacaftor every 12 hours (q12h) for 14 days, then crossed over to receive the alternate dose for another 14 days.
Ivacaftor Group B
EXPERIMENTALSubjects in Part 1 who first received 75 mg or 150 mg of ivacaftor q12h for 14 days then crossed over to receive the alternate dose for another 14 days.
Ivacaftor Group C
EXPERIMENTALSubjects in Part 2 who received 150 mg or 250 mg of ivacaftor q12h for 28 days.
Placebo
PLACEBO COMPARATORSubjects who received placebo in Part 1 and subjects who received placebo in Part 2.
Interventions
25 mg or 75 mg q12h for a total of 28 days (Part 1)
75 mg or 150 mg q12h for a total of 28 days (Part 1)
150 mg or 250 mg of ivacaftor q12h for 28 days (Part 2)
Eligibility Criteria
You may qualify if:
- Weighing at least 40 kg
- Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele
- Forced expiratory volume in 1 second (FEV1) of at least 40% of predicted normal for age, gender, and height
- Willing to remain on stable medication regimen for the duration of study participation
- No significant clinical laboratory abnormalities, not pregnant, and willing to use at least 2 highly effective birth control methods during Part 1 and 1 highly effective birth control method during Part 2 of the study
- No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator
You may not qualify if:
- History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
- Ongoing acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 14 days of Day 1 of the study
- History of alcohol, medication or illicit drug abuse within one year prior to Day 1
- Abnormal liver function ≥ 3x the upper limit of normal
- History of abnormal renal function (creatinine clearance \< 50 mL/min using Cockcroft-Gault equation)
- History of solid organ or hematological transplantation
- Pregnant or breast-feeding (for women)
- Ongoing participation in another therapeutic clinical trial, or prior participation in an investigational drug study without appropriate washout
- Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Vertex Pharmaceuticals Incorporatedlead
- Cystic Fibrosis Foundationcollaborator
Study Sites (15)
University of Alabama Hospital
Birmingham, Alabama, 35211, United States
Stanford University Medical Center
Palo Alto, California, 34304, United States
The Children's Hospital
Aurora, Colorado, 80045, United States
Roy J. and Lucille A. Carver College of Medicine, The University of Iowa
Iowa City, Iowa, 52242-1083, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
Pulmonary and Critical Care Medicine, Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Children's Hospital of Boston
Boston, Massachusetts, 02215, United States
Division of Pulmonary, Allergy and Critical Care Medicine, University of Minnesota
Minneapolis, Minnesota, 55455, United States
Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106, United States
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4399, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Pulmonary Critical Care, University of Washington
Seattle, Washington, 98195, United States
Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
CF Clinic, Pediatric Pulmonology and Neonatology, Medical School of Hannover
Straße, Hannover, D-30625, Germany
Related Publications (2)
Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, Sagel SD, Hornick DB, Konstan MW, Donaldson SH, Moss RB, Pilewski JM, Rubenstein RC, Uluer AZ, Aitken ML, Freedman SD, Rose LM, Mayer-Hamblett N, Dong Q, Zha J, Stone AJ, Olson ER, Ordonez CL, Campbell PW, Ashlock MA, Ramsey BW. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010 Nov 18;363(21):1991-2003. doi: 10.1056/NEJMoa0909825.
PMID: 21083385RESULTAccurso FJ, Van Goor F, Zha J, Stone AJ, Dong Q, Ordonez CL, Rowe SM, Clancy JP, Konstan MW, Hoch HE, Heltshe SL, Ramsey BW, Campbell PW, Ashlock MA. Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data. J Cyst Fibros. 2014 Mar;13(2):139-47. doi: 10.1016/j.jcf.2013.09.007.
PMID: 24660233DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Monitor
- Organization
- Vertex
Study Officials
- STUDY DIRECTOR
Medical Monitor
Vertex Pharmaceuticals Incorporated
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 5, 2007
First Posted
April 9, 2007
Study Start
May 1, 2007
Primary Completion
August 1, 2008
Study Completion
August 1, 2008
Last Updated
October 5, 2012
Results First Posted
October 5, 2012
Record last verified: 2012-10