(Study: Vertex IIS) Does Ivacaftor Alter Wild Type CFTR-Open Probability In The Sweat Gland Secretory Coil?

Sponsor
Richard Barry Moss (Other)
Overall Status
Completed
CT.gov ID
NCT02310789
Collaborator
(none)
8
1
1
24.8
0.3

Study Details

Study Description

Brief Summary

Clinical studies of lumacaftor + ivacaftor (combo therapy) produced better FEV1 (forced expiratory volume in 1 second) improvements than ivacaftor alone, without further improvement in sweat chloride results.

To help understand why sweat chloride was unresponsive, the investigators will use a newly developed sweat secretion test that provides accurate, in vivo readout of CFTR (cystic fibrosis transmembrane conductance regulator) function in the sweat gland secretory coil.

The investigators devised a protocol to determine if short courses of ivacaftor (3.5 days) will produce significant increases in WT (Wild-Type, i.e. normal) CFTR open probability by measuring CFTR-dependent sweating (C-sweat) in subjects with WT CFTR.

Condition or Disease Intervention/Treatment Phase
  • Drug: Ivacaftor
  • Drug: β-Adrenergic cocktail
  • Drug: Pilocarpine Nitrate 5%
  • Device: Macroduct sweat stimulator
N/A

Detailed Description

Cystic fibrosis (CF) is a genetic disease caused by malfunctioning of a protein called CFTR.

CF affects various organs including the sweat glands and the lungs. An FDA approved drug called ivacaftor helps some people with CF, and laboratory tests show that it produces further improvement when combined with an investigational drug called lumacaftor. However, results from clinical tests of the two drugs used together gave mixed results: lung function improved but sweat gland function did not improve. This study will measure CFTR-dependent sweat rate to test the hypothesis that CFTR in the normal sweat glands might be functioning at peak efficiency, and so can't be improved further with ivacaftor, thus accounting for the apparent discrepancy between lung function and sweat gland results. CFTR-dependent sweat rate is important to understanding CF because it is a very accurate measure of CFTR function.

Study Design

Study Type:
Interventional
Actual Enrollment :
8 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
(Study: Vertex IIS) A Study To Access the Effects of Ivacaftor on Wild Type CFTR-Open Probability (PO) In The Sweat Gland Secretory Coil
Actual Study Start Date :
Jul 31, 2015
Actual Primary Completion Date :
Aug 2, 2016
Actual Study Completion Date :
Aug 23, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ivacaftor

Participants will receive ivacaftor orally for 3 days, followed by 35 days off drug. Participants will repeat this cycle then receive ivacaftor for 3 additional days. For sweat testing, participants will receive β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant will also receive pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing will be done on- and off-ivacaftor.

Drug: Ivacaftor
150mg administered orally twice daily.
Other Names:
  • Kalydeco
  • Drug: β-Adrenergic cocktail
    Administered subcutaneously to induce sweating. Cocktail composed of atropine (280µM), isoproterenol (160µM), and aminophylline (20 mM).

    Drug: Pilocarpine Nitrate 5%
    Administered subcutaneously using Macroduct sweat stimulator device.

    Device: Macroduct sweat stimulator

    Outcome Measures

    Primary Outcome Measures

    1. Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate [Up to 79 days]

      CFTR-dependent sweat rate (C-sweat) was analyzed using a linear mixed model, combining on- and off-ivacaftor data.

    Secondary Outcome Measures

    1. Change Sweat Chloride Production [Up to 79 days]

      Sweat chloride concentration was measured via the traditional sweat collection methods using the pilocarpine stimulation with the Macroduct device.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Healthy adults without a Cystic Fibrosis (CF) mutation

    • Carriers with a known CF mutation

    Exclusion Criteria:
    1. Documented liver disease

    2. Participants should not be taking:

    • medicines that are strong CYP3A (Cytochrome P450, family 3, subfamily A) inducers, such as:

    • the antibiotics rifampin and rifabutin;

    • seizure medications (phenobarbital, carbamazepine, or phenytoin); and

    • the herbal supplement St. John's Wort, substantially decreases exposure of ivacaftor and may diminish effectiveness.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stanford Hospital and Clinics Stanford California United States 94305

    Sponsors and Collaborators

    • Richard Barry Moss

    Investigators

    • Principal Investigator: Jeffrey Wine, PhD, Stanford University

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Richard Barry Moss, Professor of Pediatrics at the Lucile Salter Packard Children's Hospital, Emeritus, Stanford University
    ClinicalTrials.gov Identifier:
    NCT02310789
    Other Study ID Numbers:
    • 31238
    First Posted:
    Dec 8, 2014
    Last Update Posted:
    Jan 9, 2019
    Last Verified:
    Dec 1, 2018
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ivacaftor
    Arm/Group Description Participants received ivacaftor orally for 3 days, followed by 35 days off drug. Participants repeated this cycle then received ivacaftor for 3 additional days. For sweat testing, participants received β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant also received pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing was done on- and off-ivacaftor.
    Period Title: Overall Study
    STARTED 8
    COMPLETED 7
    NOT COMPLETED 1

    Baseline Characteristics

    Arm/Group Title Ivacaftor
    Arm/Group Description Participants received ivacaftor orally for 3 days, followed by 35 days off drug. Participants repeated this cycle then received ivacaftor for 3 additional days. For sweat testing, participants received β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant also received pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing was done on- and off-ivacaftor.
    Overall Participants 8
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    7
    87.5%
    >=65 years
    1
    12.5%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    46.5
    Sex: Female, Male (Count of Participants)
    Female
    5
    62.5%
    Male
    3
    37.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    12.5%
    Not Hispanic or Latino
    7
    87.5%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    8
    100%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    8
    100%
    Healthy Volunteers (Count of Participants)
    Count of Participants [Participants]
    8
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Dependent Sweat Rate
    Description CFTR-dependent sweat rate (C-sweat) was analyzed using a linear mixed model, combining on- and off-ivacaftor data.
    Time Frame Up to 79 days

    Outcome Measure Data

    Analysis Population Description
    Participants with available data were included in the analysis.
    Arm/Group Title Ivacaftor
    Arm/Group Description Participants received ivacaftor orally for 3 days, followed by 35 days off drug. Participants repeated this cycle then received ivacaftor for 3 additional days. For sweat testing, participants received β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant also received pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing was done on- and off-ivacaftor.
    Measure Participants 7
    1% β-adrenergic stimulation
    16.45
    (2.25)
    Full β-adrenergic stimulation
    6.60
    (2.97)
    2. Secondary Outcome
    Title Change Sweat Chloride Production
    Description Sweat chloride concentration was measured via the traditional sweat collection methods using the pilocarpine stimulation with the Macroduct device.
    Time Frame Up to 79 days

    Outcome Measure Data

    Analysis Population Description
    Participants with available data were included in the analysis.
    Arm/Group Title Ivacaftor
    Arm/Group Description Participants received ivacaftor orally for 3 days, followed by 35 days off drug. Participants repeated this cycle then received ivacaftor for 3 additional days. For sweat testing, participants received β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant also received pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing was done on- and off-ivacaftor.
    Measure Participants 7
    On ivacaftor
    25.1
    (11.4)
    Off Ivacaftor
    24.9
    (6.1)

    Adverse Events

    Time Frame Up to 79 days
    Adverse Event Reporting Description
    Arm/Group Title Ivacaftor
    Arm/Group Description Participants received ivacaftor orally for 3 days, followed by 35 days off drug. Participants repeated this cycle then received ivacaftor for 3 additional days. For sweat testing, participants received β-adrenergic cocktail to stimulated sweating, at both 1% stimulation strength and full stimulation strength. Each participant also received pilocarpine nitrate 5% administered by Macroduct sweat stimulator device. Sweat stimulation testing was done on- and off-ivacaftor.
    All Cause Mortality
    Ivacaftor
    Affected / at Risk (%) # Events
    Total 0/8 (0%)
    Serious Adverse Events
    Ivacaftor
    Affected / at Risk (%) # Events
    Total 0/8 (0%)
    Other (Not Including Serious) Adverse Events
    Ivacaftor
    Affected / at Risk (%) # Events
    Total 1/8 (12.5%)
    Skin and subcutaneous tissue disorders
    Subcutaneous induration 1/8 (12.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Jeff Wine, PhD
    Organization Stanford University
    Phone 650-725-2462
    Email wine@stanford.edu
    Responsible Party:
    Richard Barry Moss, Professor of Pediatrics at the Lucile Salter Packard Children's Hospital, Emeritus, Stanford University
    ClinicalTrials.gov Identifier:
    NCT02310789
    Other Study ID Numbers:
    • 31238
    First Posted:
    Dec 8, 2014
    Last Update Posted:
    Jan 9, 2019
    Last Verified:
    Dec 1, 2018