GLPG2737 on Top of Orkambi in Subjects With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— PELICAN  

Official title:

A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate GLPG2737 in Orkambi-treated Subjects With Cystic Fibrosis Homozygous for the F508del Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03474042
• Other study ID #: GLPG2737-CL-202
• Secondary ID: 2017-002181-42
• Status: Completed
• Phase: Phase 2
• Start date: November 29, 2017
• Est. completion date: April 10, 2018

Study information

• Verified date: June 2018
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate GLPG2737 administered orally b.i.d. for 28 days to adult male and female subjects with a confirmed diagnosis of cystic fibrosis homozygous for the F508del CFTR mutation and on stable treatment with Orkambi.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 10, 2018
• Est. primary completion date: April 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female subject =18 years of age on the day of signing the ICF.

• A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation.

• Stable intake of physician prescribed Orkambi (lumacaftor 400 mg/ivacaftor 250 mg b.i.d.) for at least 12 weeks prior to the first study drug administration, and planned continuation of Orkambi for the duration of the study.

• FEV1 =40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator).

• Sweat chloride concentration =60 mmol/L at screening.

Exclusion Criteria:

• History of serious allergic reaction to any drug as determined by the investigator (e.g., anaphylaxis requiring hospitalization) and/or known sensitivity to any component of the study drug.

• 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 (including rhinosinusitis) requiring a change in therapy within 4 weeks prior to the first study drug administration.

• History of hepatic cirrhosis with portal hypertension (e.g.,signs/symptoms of splenomegaly, esophageal varices, etc.).

• Abnormal liver function test at screening, defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/or gammaglutamyl transferase (GGT) =3 x the upper limit of normal (ULN), and/or total bilirubin =1.5 x the ULN at screening.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• GLPG2737
GLPG2737 oral capsules administered twice daily for 28 days on top of Orkambi.
• Placebo
Placebo oral capsules administered twice daily for 28 days on top of Orkambi.

Locations

Country	Name	City	State
Germany	Study Site II	Berlin
Germany	Study Site X	Dresden
Germany	Study Site III	Essen
Germany	Study Site IV	Frankfurt
Germany	Study Site I	Heidelberg
Germany	Study Site V	Köln
Germany	Study Site VI	München
Germany	Study Site IX	Stuttgart
Germany	Study Site VIII	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in sweat chloride concentration compared to placebo	To assess Change from baseline in sweat chloride concentration compared to placebo.	Between day 1 pre-morning dose and Day 28.
Secondary	Change versus placebo in the proportion of subjects with adverse events.	To assess safety and tolerability by the number and percentage of subjects with adverse events.	Between Day 1 and 3 weeks after the last dose.
Secondary	Change from baseline in sweat chloride concentration.	To assess the change from baseline in sweat chloride concentration.	From baseline (pre-morning dose on Day 1) through 28 days.
Secondary	Change in percent predicted forced expiratory volume in 1 second (FEV1).	To assess the change from baseline in percent predicted forced expiratory volume in 1 second (FEV1).	From baseline (pre-morning dose on Day 1) through 28 days.
Secondary	Change in the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R).	To assess the change from baseline in the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R).	From baseline (pre-morning dose on Day 1) through 28 days.
Secondary	Maximum observed plasma concentration of GLPG2737 (Cmax)	To characterize the PK of GLPG2737 and its active metabolite, ivacaftor, and lumacaftor.	Between day 1 pre-dose and day 14.
Secondary	Area under the plasma concentration-time curve from time zero until 8 hours (AUC0-8h) post-dose calculated by the linear up - logarithmic down trapezoidal rule (on Day 14)	To characterize the PK of GLPG2737 and its active metabolite G1125498 (M4), ivacaftor, and lumacaftor.	Between day 1 pre-dose and day 14.
Secondary	Trough plasma concentration observed at the end of the dosing interval (Ctrough).	To characterize the PK of GLPG2737 and its active metabolite G1125498 (M4), ivacaftor, and lumacaftor.	Between day 1 pre-dose and day 28.