Trial Outcomes & Findings for Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690 in Subjects With Idiopathic Pulmonary Fibrosis (IPF) (NCT NCT02738801)

NCT ID: NCT02738801

Last Updated: 2020-11-06

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

From screening up to Day 98

Results posted on

2020-11-06

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Once Daily (QD) Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Overall Study STARTED	6	17
Overall Study COMPLETED	5	15
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Once Daily (QD) Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Overall Study Adverse Event	1	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo QD n=6 Participants Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD n=17 Participants Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.	Total n=23 Participants Total of all reporting groups
Age, Continuous	64.0 years n=5 Participants	67.0 years n=7 Participants	66.0 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	17 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From screening up to Day 98

Population: Safety Population: all randomized participants who received at least one dose of GLPG1690.

Outcome measures

Outcome measures
Measure	Placebo QD n=6 Participants Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD n=17 Participants Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Number of Patients With Treatment-Emergent Adverse Events (AEs)	4 Participants	11 Participants

PRIMARY outcome

Timeframe: Baseline, predose on Days 7, 14, 28, 56, 84, and 98 (or at early discontinuation), and at 1.5, 4, and 6 hours postdose on Day 28

Population: Pharmacokinetic (PK) Analysis Set: all randomized participants who received at least one dose of GLPG1690 and for whom evaluable PK data were available. Excludes 1 patient who withdrew because of an AE prior to Week 1 (and had only PK concentrations for baseline and early discontinuation) and 1 patient with only a single predose sample at Week 4

Outcome measures

Outcome measures
Measure	Placebo QD n=15 Participants Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Mean Maximum Observed Plasma Concentration (Cmax; Micrograms Per Milliliter [µg/mL]) of GLPG1690	6.06 µg/mL Standard Deviation 4.92	—

PRIMARY outcome

Timeframe: Baseline, predose on Days 7, 14, 28, 56, 84, and 98 (or at early discontinuation), and at 1.5, 4, and 6 hours postdose on Day 28

Population: PK Analysis Population; excludes 1 patient who withdrew because of an AE prior to Week 1 (and had only PK concentrations for baseline and early discontinuation) and 1 patient with only a single predose sample at Week 4.

Outcome measures

Outcome measures
Measure	Placebo QD n=15 Participants Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Median Time to Occurrence of GLPG1690 Cmax (Tmax; Hours [h])	4 hours Interval 1.5 to 6.0	—

PRIMARY outcome

Timeframe: Baseline, predose on Days 7, 14, 28, 56, 84, and 98 (or at early discontinuation), and at 1.5, 4, and 6 hours postdose on Day 28

Outcome measures

Outcome measures
Measure	Placebo QD n=15 Participants Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Mean Area Under the Plasma Concentration-Time Curve (AUC[t]; µg.h/mL) of GLPG1690	55.6 µg.h/mL Standard Deviation 46.6	—

PRIMARY outcome

Timeframe: Baseline, predose on Days 7, 14, 28, 56, 84, and 98 (or at early discontinuation), and at 1.5, 4, and 6 hours postdose on Day 28

Outcome measures

Outcome measures
Measure	Placebo QD n=15 Participants Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Mean GLPG1690 Plasma Concentration Observed at Predose (Ctrough; µg/mL)	0.624 µg/mL Standard Deviation 0.846	—

PRIMARY outcome

Timeframe: Baseline (Day -1), predose and 1.5 and 6 hours postdose on Day 28, predose on Day 84, and Day 98 (or early discontinuation)

Population: Pharmacodynamic (PD) Population: all randomized participants who received at least one dose of GLPG1690 and had at least one postbaseline assessment with PD data. Only patients with assessments at both baseline and the pre-specified visit(s) were included in the analysis.

LPA species C18:2 concentrations were determined in blood using a validated liquid chromatography tandem mass spectometry (LC/MS-MS) method. The baseline reference timepoint was Day -1 (mean of the pre-dosing duplicates).

Outcome measures

Outcome measures
Measure	Placebo QD n=6 Participants Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD n=17 Participants Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood Baseline	0.4180 peak area ratio Standard Error 0.1088	0.3311 peak area ratio Standard Error 0.0670
Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood Day 28	0.3650 peak area ratio Standard Error 0.0895	0.1476 peak area ratio Standard Error 0.0380
Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood Day 28 (1.5 hours postdose)	0.4071 peak area ratio Standard Error 0.1352	0.0479 peak area ratio Standard Error 0.0120
Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood Day 28 (6 hours postodse)	0.3402 peak area ratio Standard Error 0.1373	0.0314 peak area ratio Standard Error 0.0046
Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood Day 84	0.4080 peak area ratio Standard Error 0.1090	0.0898 peak area ratio Standard Error 0.0160
Mean Peak Area Ratio of Lysophosphatidic Acid (LPA) C18:2 Species in Blood Day 98	0.4672 peak area ratio Standard Error 0.1647	0.5172 peak area ratio Standard Error 0.1660

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 84

Population: PD Population; only patients with assessments at both baseline and the pre-specified visit were included in the analysis.

LPA species C18:2 concentrations were determined in BALF using a validated LC/MS-MS method. The baseline reference timepoint was Day -1 (mean of the pre-dosing duplicates).

Outcome measures

Outcome measures
Measure	Placebo QD n=6 Participants Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD n=17 Participants Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Mean Peak Area Ratio of LPA C18:2 Species in Bronchoalveolar Lavage Fluid (BALF) Baseline	0.0026 peak area ratio Standard Error 0.0011	0.0009 peak area ratio Standard Error 0.0002
Mean Peak Area Ratio of LPA C18:2 Species in Bronchoalveolar Lavage Fluid (BALF) Day 84	0.0035 peak area ratio Standard Error 0.0028	0.0011 peak area ratio Standard Error 0.0002

Adverse Events

Placebo QD

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

GLPG1690 600 mg QD

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo QD n=6 participants at risk Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD n=17 participants at risk Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Cardiac disorders Atrioventricular block second degree	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Infections and infestations Lower respiratory tract infection	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Infections and infestations Urinary tract infection	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Renal and urinary disorders Acute kidney injury	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)

Other adverse events

Additional Information

Evelyn Fox

Galapagos NV

Phone: 003215342900

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator must agree that before publishing or communicating any results of the trial, the sponsor has at least 60 days for full review of the information prior to submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo QD n=6 participants at risk Participants received matching oral capsules QD for 12 weeks.	GLPG1690 600 mg QD n=17 participants at risk Participants received 600 mg GLPG1690, administered as oral capsules QD for 12 weeks.
Infections and infestations Lower respiratory tract infection	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	11.8% 2/17 • From Screening to final follow-up visit (Day 98)
Infections and infestations Nasopharyngitis	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	11.8% 2/17 • From Screening to final follow-up visit (Day 98)
Infections and infestations Infected cyst	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Infections and infestations Pyelonephritis acute	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Infections and infestations Respiratory tract infection	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Infections and infestations Upper respiratory tract infection	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Infections and infestations Orchitis	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Infections and infestations Urinary tract infection	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	11.8% 2/17 • From Screening to final follow-up visit (Day 98)
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	11.8% 2/17 • From Screening to final follow-up visit (Day 98)
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	11.8% 2/17 • From Screening to final follow-up visit (Day 98)
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Respiratory, thoracic and mediastinal disorders Haemothorax	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
General disorders Fatigue	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
General disorders Peripheral swelling	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Investigations Blood creatinine increased	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Investigations Gamma-glutamyltransferase increased	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Investigations Electrocardiogram PR prolongation	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Musculoskeletal and connective tissue disorders Joint swelling	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Musculoskeletal and connective tissue disorders Osteoarthritis	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Nervous system disorders Headache	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Nervous system disorders Loss of consciousness	0.00% 0/6 • From Screening to final follow-up visit (Day 98)	5.9% 1/17 • From Screening to final follow-up visit (Day 98)
Cardiac disorders Bradycardia	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Renal and urinary disorders Acute kidney injury	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Renal and urinary disorders Dysuria	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)
Vascular disorders Orthostatic hypotension	16.7% 1/6 • From Screening to final follow-up visit (Day 98)	0.00% 0/17 • From Screening to final follow-up visit (Day 98)