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A Study Looking at the Safety, Tolerability and Efficacy of the Combination of the Study Drugs GLPG2451 and GLPG2222 With or Without GLPG2737 in Patients With Cystic Fibrosis. (FALCON)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03540524
Recruitment Status : Completed
First Posted : May 30, 2018
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
Galapagos NV

Tracking Information
First Submitted Date  ICMJE April 27, 2018
First Posted Date  ICMJE May 30, 2018
Last Update Posted Date April 8, 2019
Actual Study Start Date  ICMJE May 31, 2018
Actual Primary Completion Date March 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2018)
  • Number of subjects with adverse events. [ Time Frame: Up to 24 weeks after the last dose ]
    To assess safety and tolerability of doses of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I and Part II).
  • Maximum observed plasma concentration (Cmax). [ Time Frame: Day 14 ]
    To characterize the pharmacokinetics (PK) of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).
  • Maximum observed plasma concentration (Cmax). [ Time Frame: Day 28 ]
    To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).
  • Area under the plasma concentration-time curve from time zero until 24 hours (AUC0-24h). [ Time Frame: Day 14 ]
    To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).
  • Area under the plasma concentration-time curve from time zero until 24 hours (AUC0-24h). [ Time Frame: Day 28 ]
    To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).
  • Trough plasma concentration observed at the end of the dosing interval (24 hours post-dose) (Ctrough). [ Time Frame: Between Day 2 and Day 28 ]
    To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I and Part II).
  • Change from baseline in sweat chloride concentration. [ Time Frame: Between Day 1 pre-dose and Day 28 ]
    To assess changes in sweat chloride concentration after administration of the combination of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part II).
  • Change from baseline in percent predicted FEV1. [ Time Frame: Between Day 1 pre-dose and Day 28 ]
    To assess changes in percent predicted FEV1 after administration of the combination of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part II).
Original Primary Outcome Measures  ICMJE
 (submitted: May 16, 2018)
  • Number of subjects with adverse events. [ Time Frame: Up to 24 weeks after the last dose ]
    To assess safety and tolerability of doses of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I and Part II).
  • Maximum observed plasma concentration (Cmax). [ Time Frame: Day 14 ]
    To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).
  • Maximum observed plasma concentration (Cmax). [ Time Frame: Day 28 ]
    To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).
  • Area under the plasma concentration-time curve from time zero until 24 hours (AUC0-24h). [ Time Frame: Day 14 ]
    To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).
  • Area under the plasma concentration-time curve from time zero until 24 hours (AUC0-24h). [ Time Frame: Day 28 ]
    To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).
  • Trough plasma concentration observed at the end of the dosing interval (24 hours post-dose) (Ctrough). [ Time Frame: Between Day 2 and Day 28 ]
    To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I and Part II).
  • Change from baseline in sweat chloride concentration. [ Time Frame: Between Day 1 pre-dose and Day 28 ]
    To assess changes in sweat chloride concentration after administration of the combination of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part II).
  • Change from baseline in percent predicted FEV1. [ Time Frame: Between Day 1 pre-dose and Day 28 ]
    To assess changes in percent predicted FEV1 after administration of the combination of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part II).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2018)
  • Change from baseline in sweat chloride concentration. [ Time Frame: Between Day 1 pre-dose and Day 28 ]
    To assess changes in sweat chloride concentration after administration of the combination of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).
  • Change from baseline in percent predicted FEV1. [ Time Frame: Between Day 1 pre-dose and Day 28 ]
    To assess changes in percent predicted FEV1 after administration of the combination of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Looking at the Safety, Tolerability and Efficacy of the Combination of the Study Drugs GLPG2451 and GLPG2222 With or Without GLPG2737 in Patients With Cystic Fibrosis.
Official Title  ICMJE Assessment of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses of the Combination of GLPG2451 and GLPG2222, With or Without GLPG2737, in Adult Subjects With Cystic Fibrosis
Brief Summary This is a Phase Ib, multi-center, open-label, nonrandomized multiple cohorts study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of a combination treatment of GLPG2451 and GLPG2222, with and without GLPG2737, in adult subjects with Cystic Fibrosis.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • Drug: GLPG2451 dose regimen A
    GLPG2451 oral suspension, daily.
  • Drug: GLPG2451 dose regimen B
    GLPG2451 oral suspension, daily.
  • Drug: GLPG2222
    GLPG2222 tablet for oral use, daily.
  • Drug: GLPG2737
    GLPG2737 capsules for oral use, daily.
Study Arms  ICMJE
  • Experimental: Cohort A - F508del homozygous
    Dual combination (GLPG2451 and GLPG2222) will be administered for 14 days, followed by the triple combination (GLPG2451, GLPG2222 and GLPG2737) for 14 days, without washout in between the sequential treatment periods.( Study Part I)
    Interventions:
    • Drug: GLPG2451 dose regimen A
    • Drug: GLPG2222
    • Drug: GLPG2737
  • Experimental: Cohort B - F508del heterozygous/potentiator nonresponsive
    Dual combination (GLPG2451 and GLPG2222) will be administered for 14 days, followed by the triple combination (GLPG2451, GLPG2222 and GLPG2737) for 14 days, without washout in between the sequential treatment periods. (study Part II)
    Interventions:
    • Drug: GLPG2451 dose regimen B
    • Drug: GLPG2222
    • Drug: GLPG2737
  • Experimental: Cohort C - F508del homozygous
    Dual combination (GLPG2451 and GLPG2222) will be administered for 14 days, followed by the triple combination (GLPG2451, GLPG2222 and GLPG2737) for 14 days, without washout in between the sequential treatment periods. (Study Part II)
    Interventions:
    • Drug: GLPG2451 dose regimen B
    • Drug: GLPG2222
    • Drug: GLPG2737
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 26, 2018)
10
Original Estimated Enrollment  ICMJE
 (submitted: May 16, 2018)
24
Actual Study Completion Date  ICMJE March 11, 2019
Actual Primary Completion Date March 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female or male subject ≥18 years of age, on the day of signing the Informed Consent Form (ICF)
  • Confirmed clinical diagnosis of cystic fibrosis (CF) (documented in the subject's medical record).
  • Eligible cystic fibrosis transmembrane conductance regulator (CFTR) genotype at screening:

    • Cohort A: Homozygous for the F508del CFTR mutation
    • Cohort B: Heterozygous for the F508del CFTR mutation with a potentiator non-responsive mutation on the second allele
    • Cohort C: Homozygous for the F508del CFTR mutation
  • A body weight of ≥40 kg at screening.
  • Stable concomitant medication for pulmonary health for CF for at least 4 weeks prior to the first study drug administration and planned continuation of the same concomitant medication for the duration of the dosing period of the study. Subjects with diabetes mellitus and/or pancreatic insufficiency are eligible for the study provided they are on stable treatment (e.g. medication, diet, pancreatic enzyme replacement therapy) for at least 4 weeks prior to the first study drug administration in the opinion of the investigator.
  • Forced expiratory volume in 1 second (FEV1): 40% ≤ FEV1 ≤ 90% of predicted normal for age, sex, and height at screening (pre- or post bronchodilator) at screening.
  • Sweat chloride concentration ≥60 mmol/L at screening.
  • Non-smoker and non-user of any nicotine and or cannabis containing products. A non-smoker is defined as an individual who has abstained from smoking for at least 1 year prior to the screening. A non-user is defined as an individual who has abstained from any nicotine containing products for at least 1 year prior to the screening.

Exclusion Criteria:

  • History of or ongoing allergic bronchopulmonary aspergillosis.
  • Medical history of cataract (or lens opacity) and/or glaucoma.
  • Cataract (or lens opacity) and/or glaucoma determined by an ophthalmologist during the screening period.
  • Unstable pulmonary status or respiratory tract infection (including rhinosinusitis) requiring a change in therapy within 4 weeks prior to the first study drug administration.
  • History of clinically meaningful unstable or uncontrolled chronic disease that makes the subject unsuitable for inclusion in the study in the opinion of the investigator.
  • Need for supplemental oxygen during the day, and >2 L/minute while sleeping.
  • History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices).
  • History of malignancy within the past 5 years (except for basal cell carcinoma of the skin with no evidence of recurrence and/or carcinoma in situ of the cervix that has been treated with no evidence of recurrence).
  • Use of any moderate and strong inhibitor(s) or inducer(s) of CYP3A4 within 4 weeks prior to the first study drug administration (e.g., clarithromycin, itraconazole, ketoconazole, telithromycin, rifampin, carbamazepine).
  • Use of CFTR modulator therapy (e.g., lumacaftor and/or ivacaftor) within 4 weeks prior to the first study drug administration.
  • Use of any oral corticosteroid within 3 months of screening; or history of oral corticosteroid use for ≥30 days (cumulative) within 2 years of screening.
  • Abnormal liver function test at screening; defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/or gamma-glutamyl transferase (GGT) ≥3× the upper limit of normal (ULN); and/or total bilirubin ≥1.5× the ULN.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Bulgaria,   Germany,   Greece,   Netherlands,   Serbia,   Sweden,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03540524
Other Study ID Numbers  ICMJE GLPG2737-CL-105
2017-001067-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Galapagos NV
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Galapagos NV
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Olivier Van de Steen, MD MBA Galapagos NV
PRS Account Galapagos NV
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP