Cystic Fibrosis
Conditions
Brief summary
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.
Interventions
DRUGGLPG2222 50 mg
Oral tablet(s) containing GLPG2222
DRUGGLPG2222 100 mg
Oral tablet(s) containing GLPG2222
DRUGPlacebo
Matching oral tablet(s) containing placebo
DRUGGLPG2222 200 mg
Oral tablet(s) containing GLPG2222
DRUGGLPG2222 400 mg
Oral tablet(s) containing GLPG2222
Sponsors
Galapagos NV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF). 2. A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation 3. Weight ≥ 40 kg. 4. Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline 5. Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening
Exclusion criteria
1. 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. 2. Unstable pulmonary status or respiratory tract infection requiring a change in therapy within 4 weeks of baseline. 3. Need for supplemental oxygen during the day, and \>2 liters per minute (LPM) while sleeping. 4. Use of CFTR modulator therapy (e.g. lumacaftor or ivacaftor) within 4 weeks prior to the first study drug administration. 5. History of hepatic cirrhosis with portal hypertension. 6. 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) 7. Estimated creatinine clearance \< 60 mL/min using the Cockcroft-Gault formula at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events | First administration (Day 1) through Follow-up (Day 43) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29 | Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation | 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. |
| Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29 | Prior to dosing on Days 1 and 29, or at early discontinuation | 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. |
| Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222 | Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29 | 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. |
| Mean Change From Baseline in Sweat Chloride Concentration at Day 29 | Prior to dosing on Days 1 and 29, or at early discontinuation | 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). |
| Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h]) | Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29 | 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. |
| 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 | Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29 | 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. |
| Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL) | Days 15 and 29 (predose) | 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. |
Countries
Belgium, Netherlands, Serbia, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pooled Placebo Participants received three matching placebo tablets orally, QD for 29 days. | 11 |
| Cohort A: GLPG2222 50 mg QD Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets, orally, QD for 29 days. | 10 |
| Cohort A: GLPG2222 100 mg QD Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets, orally, QD for 29 days. | 10 |
| Cohort B: GLPG2222 200 mg QD Participants received two GLPG2222 100 mg tablets and one matching placebo tablet, orally, QD for 29 days. | 14 |
| Cohort B: GLPG2222 400 mg QD Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days. | 14 |
| Total | 59 |
Baseline characteristics
| Characteristic | Pooled Placebo | Total | Cohort B: GLPG2222 400 mg QD | Cohort B: GLPG2222 200 mg QD | Cohort A: GLPG2222 100 mg QD | Cohort A: GLPG2222 50 mg QD |
|---|---|---|---|---|---|---|
| Age, Continuous | 27.0 years | 27.0 years | 26.0 years | 32.0 years | 24.0 years | 26.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 56 Participants | 13 Participants | 13 Participants | 10 Participants | 9 Participants |
| Sex: Female, Male Female | 4 Participants | 25 Participants | 5 Participants | 7 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 34 Participants | 9 Participants | 7 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 | 0 / 10 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 9 / 11 | 8 / 10 | 10 / 10 | 11 / 14 | 9 / 14 |
| serious Total, serious adverse events | 2 / 11 | 0 / 10 | 1 / 10 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events
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).
Time frame: First administration (Day 1) through Follow-up (Day 43)
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events | Any TEAE | 9 Participants |
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events | Any Serious TEAE | 2 Participants |
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Mild | 6 Participants |
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Moderate | 2 Participants |
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Severe | 1 Participants |
| Pooled Placebo | Number of Participants With Treatment-Emergent Adverse Events | Any Treatment-related TEAE | 2 Participants |
| Cohort A: GLPG2222 50 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Severe | 0 Participants |
| Cohort A: GLPG2222 50 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any Treatment-related TEAE | 2 Participants |
| Cohort A: GLPG2222 50 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any TEAE | 8 Participants |
| Cohort A: GLPG2222 50 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Mild | 4 Participants |
| Cohort A: GLPG2222 50 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Moderate | 4 Participants |
| Cohort A: GLPG2222 50 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any Serious TEAE | 0 Participants |
| Cohort A: GLPG2222 100 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Moderate | 2 Participants |
| Cohort A: GLPG2222 100 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Severe | 1 Participants |
| Cohort A: GLPG2222 100 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any TEAE | 10 Participants |
| Cohort A: GLPG2222 100 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Mild | 7 Participants |
| Cohort A: GLPG2222 100 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any Serious TEAE | 1 Participants |
| Cohort A: GLPG2222 100 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any Treatment-related TEAE | 6 Participants |
| Cohort B: GLPG2222 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Moderate | 2 Participants |
| Cohort B: GLPG2222 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any Serious TEAE | 0 Participants |
| Cohort B: GLPG2222 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Mild | 8 Participants |
| Cohort B: GLPG2222 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any Treatment-related TEAE | 5 Participants |
| Cohort B: GLPG2222 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Severe | 1 Participants |
| Cohort B: GLPG2222 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any TEAE | 11 Participants |
| Cohort B: GLPG2222 400 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Severe | 0 Participants |
| Cohort B: GLPG2222 400 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Mild | 9 Participants |
| Cohort B: GLPG2222 400 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any Serious TEAE | 0 Participants |
| Cohort B: GLPG2222 400 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any Treatment-related TEAE | 1 Participants |
| Cohort B: GLPG2222 400 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Worst TEAE Intensity=Moderate | 0 Participants |
| Cohort B: GLPG2222 400 mg QD | Number of Participants With Treatment-Emergent Adverse Events | Any TEAE | 9 Participants |
Secondary
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
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.
Time frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Population: PK Population; data were not calculable for 1 patient.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | 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 | 3850 ng.h/mL | Standard Deviation 1670 |
| Cohort A: GLPG2222 50 mg QD | 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 | 9670 ng.h/mL | Standard Deviation 3770 |
| Cohort A: GLPG2222 100 mg QD | 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 | 22900 ng.h/mL | Standard Deviation 7530 |
| Cohort B: GLPG2222 200 mg QD | 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 | 46400 ng.h/mL | Standard Deviation 25500 |
Secondary
Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29
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.
Time frame: Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29 | -1.0 % predicted FEV1 | Standard Error 1.45 |
| Cohort A: GLPG2222 50 mg QD | Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29 | 0.1 % predicted FEV1 | Standard Error 1.5 |
| Cohort A: GLPG2222 100 mg QD | Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29 | -0.3 % predicted FEV1 | Standard Error 1.51 |
| Cohort B: GLPG2222 200 mg QD | Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29 | 0.0 % predicted FEV1 | Standard Error 1.27 |
| Cohort B: GLPG2222 400 mg QD | Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29 | 1.3 % predicted FEV1 | Standard Error 1.26 |
Comparison: Day 29: GLPG2222 50 mg QD vs. Pooled Placebop-value: 0.59495% CI: [-3.1, 5.4]ANCOVA
Comparison: Day 29: GLPG2222 100 mg QD vs. Pooled Placebop-value: 0.755395% CI: [-3.5, 4.8]ANCOVA
Comparison: Day 29: GLPG2222 200 mg QD vs. Pooled Placebop-value: 0.595895% CI: [-2.9, 4.9]ANCOVA
Comparison: Day 29: GLPG2222 400 mg QD vs. Pooled Placebop-value: 0.240395% CI: [-1.6, 6.2]ANCOVA
Secondary
Mean Change From Baseline in Sweat Chloride Concentration at Day 29
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).
Time frame: Prior to dosing on Days 1 and 29, or at early discontinuation
Population: Intent-to-treat (ITT) population: all enrolled participants who received at least one dose of study drug and had at least one post-baseline assessment with efficacy data. Only participants with non-missing data at baseline were included in the analysis; 3 participants had missing sweat chloride concentration data at baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Mean Change From Baseline in Sweat Chloride Concentration at Day 29 | -2.5 mmol/L | Standard Error 2.79 |
| Cohort A: GLPG2222 50 mg QD | Mean Change From Baseline in Sweat Chloride Concentration at Day 29 | -5.8 mmol/L | Standard Error 3.08 |
| Cohort A: GLPG2222 100 mg QD | Mean Change From Baseline in Sweat Chloride Concentration at Day 29 | -6.6 mmol/L | Standard Error 3.29 |
| Cohort B: GLPG2222 200 mg QD | Mean Change From Baseline in Sweat Chloride Concentration at Day 29 | -18.3 mmol/L | Standard Error 2.49 |
| Cohort B: GLPG2222 400 mg QD | Mean Change From Baseline in Sweat Chloride Concentration at Day 29 | -8.8 mmol/L | Standard Error 2.49 |
Comparison: Day 29: GLPG2222 50 mg QD vs. Pooled Placebop-value: 0.429195% CI: [-11.6, 5]ANCOVA
Comparison: Day 29: GLPG2222 100 mg QD vs. Pooled Placebop-value: 0.347795% CI: [-12.8, 4.6]ANCOVA
Comparison: Day 29: GLPG2222 200 mg QD vs. Pooled Placebop-value: <0.000195% CI: [-23.2, -8.3]ANCOVA
Comparison: Day 29: GLPG2222 400 mg QD vs. Pooled Placebop-value: 0.099595% CI: [-13.9, 1.2]ANCOVA
Secondary
Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29
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.
Time frame: Prior to dosing on Days 1 and 29, or at early discontinuation
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29 | -2.4 units on a scale | Standard Error 3.32 |
| Cohort A: GLPG2222 50 mg QD | Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29 | 0.4 units on a scale | Standard Error 3.47 |
| Cohort A: GLPG2222 100 mg QD | Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29 | -0.7 units on a scale | Standard Error 3.48 |
| Cohort B: GLPG2222 200 mg QD | Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29 | 4.5 units on a scale | Standard Error 2.93 |
| Cohort B: GLPG2222 400 mg QD | Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29 | -0.8 units on a scale | Standard Error 2.93 |
Comparison: Day 29: GLPG2222 50 mg QD vs. Pooled Placebop-value: 0.574995% CI: [-6.9, 12.4]ANCOVA
Comparison: Day 29: GLPG2222 100 mg QD vs. Pooled Placebop-value: 0.738195% CI: [-8.1, 11.3]ANCOVA
Comparison: Day 29: GLPG2222 200 mg QD vs. Pooled Placebop-value: 0.128295% CI: [-2, 15.7]ANCOVA
Comparison: Day 29: GLPG2222 400 mg QD vs. Pooled Placebop-value: 0.721295% CI: [-7.3, 10.5]ANCOVA
Secondary
Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)
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.
Time frame: Days 15 and 29 (predose)
Population: PK Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL) | 48.1 ng/mL | Standard Deviation 33.7 |
| Cohort A: GLPG2222 50 mg QD | Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL) | 132 ng/mL | Standard Deviation 87.2 |
| Cohort A: GLPG2222 100 mg QD | Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL) | 343 ng/mL | Standard Deviation 204 |
| Cohort B: GLPG2222 200 mg QD | Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL) | 677 ng/mL | Standard Deviation 659 |
Secondary
Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222
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.
Time frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Population: Pharmacokinetic (PK) Population: all participants who were exposed to GLPG2222 and who had available and evaluable PK data (excluding all protocol violations/deviations or adverse events that may have had an impact on the PK analysis). Data were not calculable for 1 patient.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222 | 478 ng/mL | Standard Deviation 128 |
| Cohort A: GLPG2222 50 mg QD | Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222 | 1170 ng/mL | Standard Deviation 395 |
| Cohort A: GLPG2222 100 mg QD | Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222 | 2490 ng/mL | Standard Deviation 535 |
| Cohort B: GLPG2222 200 mg QD | Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222 | 5330 ng/mL | Standard Deviation 2700 |
Secondary
Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h])
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.
Time frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29
Population: PK Population; data were not calculable for 1 patient.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pooled Placebo | Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h]) | 2.0 hours |
| Cohort A: GLPG2222 50 mg QD | Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h]) | 2.0 hours |
| Cohort A: GLPG2222 100 mg QD | Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h]) | 3.0 hours |
| Cohort B: GLPG2222 200 mg QD | Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h]) | 2.0 hours |