- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03119649
A Study to Evaluate Multiple Doses of GLPG2222 in Adult Subjects With Cystic Fibrosis
October 19, 2018 updated by: Galapagos NV
A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate Multiple Doses of GLPG2222 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation
This is a Phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 4 different doses of GLPG2222 administered for 4 weeks to adult subjects with a confirmed diagnosis of CF and homozygous for the F508del Cystic Fibrosis Transmembrane conductance Regulator (CFTR) mutation.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
59
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Antwerp, Belgium
- UZ Antwerpen
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Brussels, Belgium
- UZ Brussel
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Ghent, Belgium
- UZ Gent
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Leuven, Belgium
- Uz Leuven
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Amsterdam, Netherlands
- AMC Amsterdam
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Rotterdam, Netherlands
- Erasmus Medisch Centrum
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The Hague, Netherlands
- HAGA ziekenhuis
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Utrecht, Netherlands
- UMC Utrecht
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Novi Beograd, Serbia
- Mother and child health institute of Serbia
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Barcelona, Spain
- Hospital Universitari Vall d'Hebron
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Madrid, Spain
- Hospital Universitario La Paz
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Valencia, Spain
- Hospital Universitarii Plitecnic La Fe
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Cambridge, United Kingdom
- Papworth Hospital
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Leeds, United Kingdom
- St James University Hospital
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Liverpool, United Kingdom
- Liverpool Heart and Chest Hospital
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Southampton, United Kingdom
- Southampton General Hospital
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Alabama
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Chatom, Alabama, United States, 35233
- Child Health Research Unit at UAB
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Arkansas
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Little Rock, Arkansas, United States, 72205
- University of Arkansas for Medical Sciences
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Florida
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Orlando, Florida, United States, 32803
- Central Florida Pulmonary Group
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Illinois
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Glenview, Illinois, United States, 60026
- Cystic Fibrosis Center of Chicago
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Maine
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Portland, Maine, United States, 04102
- Maine Medical Center
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Maryland
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Baltimore, Maryland, United States, 21205
- John Hopkins University School of Medicine
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South Carolina
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Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 99 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF).
- A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation
- Weight ≥ 40 kg.
- Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline
- Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening
Exclusion Criteria:
- 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.
- Unstable pulmonary status or respiratory tract infection requiring a change in therapy within 4 weeks of baseline.
- Need for supplemental oxygen during the day, and >2 liters per minute (LPM) while sleeping.
- Use of CFTR modulator therapy (e.g. lumacaftor or ivacaftor) within 4 weeks prior to the first study drug administration.
- History of hepatic cirrhosis with portal hypertension.
- 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) ≥ 3x the upper limit of normal (ULN); and/or total bilirubin (>1.5 times ULN)
- Estimated creatinine clearance < 60 mL/min using the Cockcroft-Gault formula at screening.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort A: GLPG2222 50 mg once daily (QD)
Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days.
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Oral tablet(s) containing GLPG2222
Matching oral tablet(s) containing placebo
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Experimental: Cohort A: GLPG2222 100 mg QD
Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days.
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Matching oral tablet(s) containing placebo
Oral tablet(s) containing GLPG2222
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Experimental: Cohort B: GLPG2222 200 mg QD
Participants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days.
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Matching oral tablet(s) containing placebo
Oral tablet(s) containing GLPG2222
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Experimental: Cohort B: GLPG2222 400 mg QD
Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days.
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Matching oral tablet(s) containing placebo
Oral tablet(s) containing GLPG2222
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Placebo Comparator: Cohort A Placebo
Participants received three matching placebo tablets, orally, QD for 29 days.
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Matching oral tablet(s) containing placebo
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Placebo Comparator: Cohort B Placebo
Participants received three matching placebo tablets, orally, QD for 29 days.
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Matching oral tablet(s) containing placebo
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-Emergent Adverse Events
Time Frame: First administration (Day 1) through Follow-up (Day 43)
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Number of participants with any treatment-emergent adverse events (TEAEs) and serious or treatment-related TEAEs, as well as number of patients with TEAEs by worst intensity reported (mild, moderate, or severe).
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First administration (Day 1) through Follow-up (Day 43)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Mean Change From Baseline in Sweat Chloride Concentration at Day 29
Time Frame: Prior to dosing on Days 1 and 29, or at early discontinuation
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Two sweat collections, one from each arm, were obtained.
Mean sweat chloride concentration was determined from both arms and measured as millimoles per liter (mmol/L).
Baseline was defined as the predose value on Day 1 (or the last non-missing predose measurement).
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Prior to dosing on Days 1 and 29, or at early discontinuation
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Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29
Time Frame: Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation
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Percent predicted FEV1 for age, gender, and height was determined from standardized spirometry assessments and estimated using the 2012 Global Lungs Initiative equation.
Baseline was defined as the last non-missing predose assessment on Day 1.
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Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation
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Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29
Time Frame: Prior to dosing on Days 1 and 29, or at early discontinuation
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The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis.
The respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), derived from Questions 40, 41, 42, 45, and 46 if at least 50% of the questions had non-missing data.
The scale score ranged from 0-100; higher scores indicated fewer symptoms and better health-related quality of life with a negative change indicating a worsening of symptoms.
A change of 4 is considered clinically relevant.
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Prior to dosing on Days 1 and 29, or at early discontinuation
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Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222
Time Frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
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Maximum concentration of GLPG2222 after multiple dosing (ng/ML), obtained directly from the observed concentration versus time data.
All pharmacokinetic (PK) parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.
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Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
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Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)
Time Frame: Days 15 and 29 (predose)
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Plasma concentration of GLPG2222 observed at pre-dose (ng/mL), obtained directly from the observed concentration versus time data.
Ctrough was calculated using both Day 15 and Day 29 PK data.
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Days 15 and 29 (predose)
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Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h])
Time Frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
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Time of occurrence of maximum concentration of GLPG2222 after multiple dosing (h), obtained directly from the observed concentration versus time data.
All PK parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.
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Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
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Mean Area Under the Concentration-Time Curve From Time 0 up to 24 Hours Following Multiple Dosing (AUC[0-t]; ng.h/mL) of GLPG2222
Time Frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
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Area under the concentration-time curve from time 0 up to 24 hours following multiple dosing (ng.h/mL), calculated by linear up/log down trapezoidal summation.
All PK parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.
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Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 18, 2017
Primary Completion (Actual)
October 19, 2017
Study Completion (Actual)
October 19, 2017
Study Registration Dates
First Submitted
April 11, 2017
First Submitted That Met QC Criteria
April 17, 2017
First Posted (Actual)
April 18, 2017
Study Record Updates
Last Update Posted (Actual)
November 16, 2018
Last Update Submitted That Met QC Criteria
October 19, 2018
Last Verified
October 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GLPG2222-CL-202
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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