Safety Study of Ivacaftor in Subjects With Cystic Fibrosis
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| ClinicalTrials.gov Identifier: NCT00457821 |
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Recruitment Status :
Completed
First Posted : April 9, 2007
Results First Posted : October 5, 2012
Last Update Posted : October 5, 2012
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Sponsor:
Vertex Pharmaceuticals Incorporated
Collaborator:
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cystic Fibrosis | Drug: Ivacaftor 25 mg/75 mg Drug: Ivacaftor 75 mg/150 mg Drug: Ivacaftor 150 mg or 250 mg Drug: Placebo | Phase 2 |
This was a double-blind, placebo-controlled, cross-over, multiple dose study of up to 28 days of dosing, in subjects with cystic fibrosis (CF) who have a G551D-CTFR gene mutation. Enrollment of 39 subjects occurred at 15 centers in the US, Canada, and Germany.
The study was conducted in 2 parts:
- Part 1 consisted of Group A and Group B. Subjects in Group A (10 subjects) were randomized to receive 25 mg of ivacaftor every 12 hours [q12h] (4 subjects), 75 mg of ivacaftor q12h (4 subjects), or placebo (2 subjects) for 14 days. Following a 7- to 28-day washout period, subjects who received active study drug crossed over to the alternate dose strength of ivacaftor for an additional 14 days. Placebo subjects continued to receive placebo for an additional 14 days. Subjects in Group B (10 subjects) were randomized to receive 75 mg of ivacaftor q12h (4 subjects), 150 mg of ivacaftor q12h (4 subjects), or placebo (2 subjects) for 14 days. Following a 7- to 28-day washout period, the subjects who received active study drug crossed over to the alternate dose strength of ivacaftor for an additional 14 days. Placebo subjects continued to receive placebo for an additional 14 days.
- Part 2 consisted of Group C; these subjects did not participate in Part 1. Subjects were randomized to receive 150 mg of ivacaftor q12h (7 subjects), 250 mg of ivacaftor q12h (7 subjects), or placebo (4 subjects) for a total of 28 days. Ivacaftor doses studied in Part 2 were selected following an interim pharmacokinetic/pharmacodynamic (PK/PD) and statistical analyses of data from Part 1. The 2 doses selected for Part 2 were anticipated to enable better definition of the optimal therapeutic dose.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 39 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Study Start Date : | May 2007 |
| Actual Primary Completion Date : | August 2008 |
| Actual Study Completion Date : | August 2008 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Cystic fibrosis
MedlinePlus related topics:
Cystic Fibrosis
Drug Information available for:
Ivacaftor
| Arm | Intervention/treatment |
|---|---|
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Experimental: Ivacaftor Group A
Subjects 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.
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Drug: Ivacaftor 25 mg/75 mg
25 mg or 75 mg q12h for a total of 28 days (Part 1)
Other Name: VX-770 |
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Experimental: Ivacaftor Group B
Subjects 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.
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Drug: Ivacaftor 75 mg/150 mg
75 mg or 150 mg q12h for a total of 28 days (Part 1)
Other Name: VX-770 |
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Experimental: Ivacaftor Group C
Subjects in Part 2 who received 150 mg or 250 mg of ivacaftor q12h for 28 days.
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Drug: Ivacaftor 150 mg or 250 mg
150 mg or 250 mg of ivacaftor q12h for 28 days (Part 2)
Other Name: VX-770 |
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Placebo Comparator: Placebo
Subjects who received placebo in Part 1 and subjects who received placebo in Part 2.
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Drug: Placebo
Given q12h for 28 days each in Part 1 and Part 2 of the study |
Primary Outcome Measures :
- Number of Subjects With Adverse Events (Combined Part 1 and Part 2) [ Time Frame: Baseline to Follow-up ]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.
- Number of Adverse Events (Combined Part 1 and Part 2) [ Time Frame: Baseline to Follow-up ]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.
Secondary Outcome Measures :
- Change From Baseline in Nasal Potential Difference (Combined Part 1 and Part 2) [ Time Frame: 14 days and 28 days ]The transepithelial nasal potential difference (NPD) is a direct measure of transepithelial ion transport. NPD under conditions of zero chloride concentration perfusion solution in the presence of isoproterenol was of primary interest.
- Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second [FEV1] (Combined Part 1 and Part 2) [ Time Frame: 14 days and 28 days ]
Spirometry is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
Relative change reflects the percent change from the baseline values [100% * (X-Y)/Y], where X and Y are post-baseline and baseline values, respectively.
- Change From Baseline in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score (Part 2 Only)(Respiratory Domain Score) [ Time Frame: 14 days and 28 days ]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).
- Change From Baseline in Maximum Sweat Chloride Concentration (Combined Part 1 and Part 2) [ Time Frame: 14 days and 28 days ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00457821
Locations
| United States, Alabama | |
| University of Alabama Hospital | |
| Birmingham, Alabama, United States, 35211 | |
| United States, California | |
| Stanford University Medical Center | |
| Palo Alto, California, United States, 34304 | |
| United States, Colorado | |
| The Children's Hospital | |
| Aurora, Colorado, United States, 80045 | |
| United States, Iowa | |
| Roy J. and Lucille A. Carver College of Medicine, The University of Iowa | |
| Iowa City, Iowa, United States, 52242-1083 | |
| United States, Maryland | |
| Johns Hopkins Hospital | |
| Baltimore, Maryland, United States, 21287 | |
| United States, Massachusetts | |
| Pulmonary and Critical Care Medicine, Massachusetts General Hospital | |
| Boston, Massachusetts, United States, 02114 | |
| Children's Hospital of Boston | |
| Boston, Massachusetts, United States, 02215 | |
| United States, Minnesota | |
| Division of Pulmonary, Allergy and Critical Care Medicine, University of Minnesota | |
| Minneapolis, Minnesota, United States, 55455 | |
| United States, North Carolina | |
| Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill | |
| Chapel Hill, North Carolina, United States, 27599 | |
| United States, Ohio | |
| Rainbow Babies and Children's Hospital | |
| Cleveland, Ohio, United States, 44106 | |
| United States, Pennsylvania | |
| The Children's Hospital of Philadelphia | |
| Philadelphia, Pennsylvania, United States, 19104-4399 | |
| University of Pittsburgh | |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| United States, Washington | |
| Pulmonary Critical Care, University of Washington | |
| Seattle, Washington, United States, 98195 | |
| Canada, Ontario | |
| Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children | |
| Toronto, Ontario, Canada, M5G 1X8 | |
| Germany | |
| CF Clinic, Pediatric Pulmonology and Neonatology, Medical School of Hannover | |
| Strasse, Hannover, Germany, D-30625 | |
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Cystic Fibrosis Foundation Therapeutics
Investigators
| Study Director: | Medical Monitor | Vertex Pharmaceuticals Incorporated |
Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Vertex Pharmaceuticals Incorporated |
| ClinicalTrials.gov Identifier: | NCT00457821 History of Changes |
| Other Study ID Numbers: |
VX06-770-101 |
| First Posted: | April 9, 2007 Key Record Dates |
| Results First Posted: | October 5, 2012 |
| Last Update Posted: | October 5, 2012 |
| Last Verified: | October 2012 |
Keywords provided by Vertex Pharmaceuticals Incorporated:
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G551D mutation Fibrosis Pancreatic Diseases Digestive System Diseases Lung Diseases |
Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Pathologic Processes |
Additional relevant MeSH terms:
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Fibrosis Cystic Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases |
Genetic Diseases, Inborn Infant, Newborn, Diseases Ivacaftor Chloride Channel Agonists Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action |