Safety Study of Ivacaftor in Subjects With Cystic Fibrosis

NCT ID: NCT00457821

Last Updated: 2012-10-05

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-05-31

Study Completion Date

2008-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cystic Fibrosis

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Ivacaftor 25 mg/75 mg

Intervention Type DRUG

25 mg or 75 mg q12h for a total of 28 days (Part 1)

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.

Group Type EXPERIMENTAL

Ivacaftor 75 mg/150 mg

Intervention Type DRUG

75 mg or 150 mg q12h for a total of 28 days (Part 1)

Ivacaftor Group C

Subjects in Part 2 who received 150 mg or 250 mg of ivacaftor q12h for 28 days.

Group Type EXPERIMENTAL

Ivacaftor 150 mg or 250 mg

Intervention Type DRUG

150 mg or 250 mg of ivacaftor q12h for 28 days (Part 2)

Placebo

Subjects who received placebo in Part 1 and subjects who received placebo in Part 2.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Given q12h for 28 days each in Part 1 and Part 2 of the study

Interventions

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Ivacaftor 25 mg/75 mg

25 mg or 75 mg q12h for a total of 28 days (Part 1)

Intervention Type DRUG

Ivacaftor 75 mg/150 mg

75 mg or 150 mg q12h for a total of 28 days (Part 1)

Intervention Type DRUG

Ivacaftor 150 mg or 250 mg

150 mg or 250 mg of ivacaftor q12h for 28 days (Part 2)

Intervention Type DRUG

Placebo

Given q12h for 28 days each in Part 1 and Part 2 of the study

Intervention Type DRUG

Other Intervention Names

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VX-770 VX-770 VX-770

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cystic Fibrosis Foundation

OTHER

Sponsor Role collaborator

Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor

Role: STUDY_DIRECTOR

Vertex Pharmaceuticals Incorporated

Locations

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University of Alabama Hospital

Birmingham, Alabama, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

The Children's Hospital

Aurora, Colorado, United States

Site Status

Roy J. and Lucille A. Carver College of Medicine, The University of Iowa

Iowa City, Iowa, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Pulmonary and Critical Care Medicine, Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Children's Hospital of Boston

Boston, Massachusetts, United States

Site Status

Division of Pulmonary, Allergy and Critical Care Medicine, University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Pulmonary Critical Care, University of Washington

Seattle, Washington, United States

Site Status

Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

CF Clinic, Pediatric Pulmonology and Neonatology, Medical School of Hannover

Straße, Hannover, Germany

Site Status

Countries

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United States Canada Germany

References

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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.

Reference Type RESULT
PMID: 21083385 (View on PubMed)

Accurso 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.

Reference Type DERIVED
PMID: 24660233 (View on PubMed)

Related Links

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Other Identifiers

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VX06-770-101

Identifier Type: -

Identifier Source: org_study_id