Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01685801
First received: September 6, 2012
Last updated: April 30, 2015
Last verified: April 2015
  Purpose

This study is a multiple within participant crossover study to evaluate the effect of ivacaftor on lung function in participants aged 12 years and older with cystic fibrosis (CF) who have phenotypic or molecular evidence of residual CF transmembrane conductance regulator (CFTR) function.


Condition Intervention Phase
Cystic Fibrosis
Drug: Ivacaftor
Drug: Placebo-matched-to-ivacaftor tablet
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: A Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis, Residual CFTR Function, and FEV1 ≥40% Predicted

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment [ Time Frame: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms) ] [ Designated as safety issue: No ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).


Secondary Outcome Measures:
  • Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment [ Time Frame: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms) ] [ Designated as safety issue: No ]
    LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

  • Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57 [ Time Frame: Open-label Baseline, Open-label Day 57 ] [ Designated as safety issue: No ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

  • Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57 [ Time Frame: Open-label Baseline, Open-label Day 57 ] [ Designated as safety issue: No ]
    LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

  • Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57 [ Time Frame: Study Baseline, Open-label Day 57 ] [ Designated as safety issue: No ]
    Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

  • Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57 [ Time Frame: Open-label Baseline, Open-label Day 57 ] [ Designated as safety issue: No ]
    Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study drug through completion of follow-up visit (up to 26 weeks) ] [ Designated as safety issue: Yes ]
    Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a "Washout Period" AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.


Enrollment: 24
Study Start Date: September 2012
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Drug: Ivacaftor
150 milligram (mg) tablet orally every 12 hours up to 12 weeks.
Other Name: Kalydeco, VX-770
Drug: Placebo-matched-to-ivacaftor tablet
Orally every 12 hours up to 4 weeks.
Experimental: Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Drug: Ivacaftor
150 milligram (mg) tablet orally every 12 hours up to 12 weeks.
Other Name: Kalydeco, VX-770
Drug: Placebo-matched-to-ivacaftor tablet
Orally every 12 hours up to 4 weeks.
Experimental: Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Drug: Ivacaftor
150 milligram (mg) tablet orally every 12 hours up to 12 weeks.
Other Name: Kalydeco, VX-770
Drug: Placebo-matched-to-ivacaftor tablet
Orally every 12 hours up to 4 weeks.
Experimental: Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Drug: Ivacaftor
150 milligram (mg) tablet orally every 12 hours up to 12 weeks.
Other Name: Kalydeco, VX-770
Drug: Placebo-matched-to-ivacaftor tablet
Orally every 12 hours up to 4 weeks.

Detailed Description:

CFTR Mutations associated with residual function or defective messenger ribonucleic acid (mRNA) splicing include the following:

R117H, E56K, P67L, D110E, D110H, R117C, R347H, R352Q, A455E, D579G, S945L, L206W, R1070W, F1074L, D1152H, S1235R, D1270N, 2789+5G->A, 3849+10kbC->T, 3272-26A->G, 711+5G->A, 3120G->A, 1811+1.6kbA->G, 711+3A->G, 1898+3A->G, 1898+1G->A, 1717-1G->A, 1717-8G->A, 1342-2A->C, 405+3A->C, 1716G/A 1811+1G->C, 1898+5G->T, 3850-3T->G, IVS14b+5G->A, 1898+1G->T, 4005+2T->C, 621+3A->G, 621+1G->T.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female participants with confirmed diagnosis of CF
  • Clinical evidence of residual CFTR function based on any 1 of the following: 1) Clinically documented residual exocrine pancreatic function, 2) Sweat chloride value less than equal to (<=) 80 millimole per liter (mmol/L) at screening, or 3) Age of diagnosis greater than equal to (>=) 12 years and at least 1 copy of a CFTR mutation associated with residual CFTR function or defective mRNA splicing
  • FEV1 >= 40 percent (%)
  • 12 years of age or older
  • Willing to agree to meet the contraception requirements
  • Able to swallow tablets

Exclusion Criteria:

  • A copy of any of the following CFTR mutations: G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, or G1349D
  • Unable to perform spirometry
  • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1
  • Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685801

Locations
United States, Colorado
Denver, Colorado, United States
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Investigators
Principal Investigator: Jerry Nick, MD National Jewish Health
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01685801     History of Changes
Other Study ID Numbers: VX12-770-113
Study First Received: September 6, 2012
Results First Received: April 30, 2015
Last Updated: April 30, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 30, 2015