Short Term Effects of Ivacaftor in Non-G551D Cystic Fibrosis Patients

NCT01784419 | Completed Results

• 1 other identifier: FS-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study of the short-term effects of ivacaftor on sweat chloride concentration and lung function in cystic fibrosis (CF) patients who fall outside current FDA approval. This new, first of its kind drug is approved for use only in CF patients with the G551D mutation in whom it safely confers considerable benefits. However, it is highly likely that CF patients with many other mutations can benefit similarly from this drug, some of whom can be identified by phenotype or genotype. We will enroll up to 30 CF subjects with clinical presentations in which there is one or more signs of residual CF channel function. The signs of residual function include: normal digestion, concentration of chloride in sweat between 55 and 85, or milder than expected CF disease in a CF patient with severe gene mutations. The primary outcome measure will be the difference in sweat chloride concentration measured in subjects on placebo and on ivacaftor. Secondary outcome measured will be lung function.

Conditions

Cystic Fibrosis

Keywords

Cystic fibrosis; Ivacaftor; Genotype; Phenotype; Sweat chloride; Pancreatic sufficient

Outcome Measures

Primary Outcomes (1)

• Sweat Chloride Concentration

  Sweat chloride concentration measured by pilocarpine iontophoresis, a standard clinical laboratory technique. Sweat collection accomplished with the Wescor Macroduct system. Sweat chloride is measured at the start and end of each study period. There are two study periods during which subjects take either ivacaftor or placebo.

  14 +/- 2 days

Secondary Outcomes (2)

• Spirometry

  14 +/- 2 days

• Multibreath Washout Testing

  14 +/- 2 days

Study Arms (2)

ivacaftor-placebo

EXPERIMENTAL

The ivacaftor-placebo arm receives a 2 week course of ivacaftor 150 mg twice daily followed by a 2 week washout period followed by a 2 week placebo course.

Drug: ivacaftor; Drug: Placebo

placebo-ivacaftor

EXPERIMENTAL

The placebo-ivacaftor arm receives a 2 week placebo course followed by a 2 week washout period followed by a 2 week course of ivacaftor 150 mg twice daily.

Drug: ivacaftor; Drug: Placebo

Interventions

ivacaftor DRUG

Eligible subjects were randomized to ivacaftor 150 mg by mouth twice a day for 14 days followed by placebo for 14 days, or vice versa. Randomization was based on a computer-generated schedule produced by the research pharmacy, which was concealed from study personnel until study completion. Ivacaftor was purchased at full retail cost and encapsulated with sucrose to match the sucrose-filled placebo capsules. Prior to beginning study drug, there was a 2-week run-in period to ensure clinical stability, assessed by modified Fuchs criteria and pulmonary function. There was a washout period of a minimum of 14 days between study drug cycles to account for carryover effect. The washout period was extended to 6 weeks for subjects on alternating cycles of inhaled antibiotics to coordinate the study drug cycle with the inhaled antibiotic cycle.

Also known as: Kalydeco, VX-770

ivacaftor-placebo; placebo-ivacaftor

Placebo DRUG

Eligible subjects were randomized to ivacaftor 150 mg by mouth twice a day for 14 days followed by placebo for 14 days, or vice versa. Randomization was based on a computer-generated schedule produced by the research pharmacy, which was concealed from study personnel until study completion. Ivacaftor was purchased at full retail cost and encapsulated with sucrose to match the sucrose-filled placebo capsules. Prior to beginning study drug, there was a 2-week run-in period to ensure clinical stability, assessed by modified Fuchs criteria and pulmonary function. There was a washout period of a minimum of 14 days between study drug cycles to account for carryover effect. The washout period was extended to 6 weeks for subjects on alternating cycles of inhaled antibiotics to coordinate the study drug cycle with the inhaled antibiotic cycle.

ivacaftor-placebo; placebo-ivacaftor

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Two mutations known to cause cystic fibrosis and a sweat chloride concentration greater than or equal to 55 mmol
• Greater than or equal to 6 years of age

You may not qualify if:

• Homozygous F508del with a sweat chloride greater than 85 mmol
• Taking medication known to interact with ivacaftor and chooses not to discontinue that medication
• Is pregnant or planning to become pregnant during the study period
• Less than 6 years of age

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• McGarry ME, Illek B, Ly NP, Zlock L, Olshansky S, Moreno C, Finkbeiner WE, Nielson DW. In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N-of-1 studies. Pediatr Pulmonol. 2017 Apr;52(4):472-479. doi: 10.1002/ppul.23659. Epub 2017 Jan 9.

  PMID: 28068001 RESULT

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ivacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Dennis W. Nielson, MD, PhD
• Organization: University of California, San Francisco

Dennis.Nielson@ucsf.edu

Study Officials

• Dennis W Nielson, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SCREENING
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2013
• First Posted: February 5, 2013
• Study Start: October 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 29, 2020
• Results First Posted: September 29, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)