Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of GLPG0974 in Subjects With Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

Exploratory, Phase II, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of GLPG0974 in Subjects With Mild to Moderate Ulcerative Colitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01829321
• Other study ID #: GLPG0974-CL-201
• Secondary ID: 2012-005521-73
• Status: Completed
• Phase: Phase 2
• First received: April 9, 2013
• Last updated: April 24, 2014
• Start date: April 2013
• Est. completion date: April 2014

Study information

• Verified date: April 2014
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlLatvia: State Agency of MedicinesSlovakia: State Institute for Drug Control
• Study type: Interventional

Clinical Trial Summary

• Approximately 45 patients suffering from mild to moderate ulcerative colitis will be examined for any side effects (safety and tolerability) that may occur when taking GLPG0974 or matching placebo (2:1 ratio) for 28 days.

• During the course of the study, patients will also be evaluated for improvement of disease activity by different efficacy measures, the amount of GLPG0974 present in the blood determined (PK) and the effects of GLPG0974 on selected biomarkers (PD) in the blood, colon biopsies and faeces will be explored.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

• Men or women between 18 to 75 years of age inclusive, on the day of signing the informed consent with a documented history of UC.

• Presence of mild-to-moderately active ulcerative colitis as evidenced by clinical signs and endoscopy.

• Medication: 5-ASA.

• Absence of infectious colitis.

Key Exclusion Criteria:

• History of sensitivity to any component of the study drug

• Any concurrent illness, condition, disability or clinically significant abnormality (including lab tests) that represents a safety risk , may affect the interpretation of data, or may prevent the subject to safely complete the assessments

• Positive serology for HIV 1 or 2 or hepatitis B or C, or any history of HIV or hepatitis.

• History of active infections requiring intravenous antibiotics within the past four weeks prior to randomization.

• History of bowel surgery, or presence or history of intestinal malignancy.

• Suspicion of Crohn's disease, indeterminate colitis, microscopic colitis, ischaemic colitis or radiation-induced colitis.

• History of lower GI bleeding disorder, other than UC.

• A history of significant psychological, neurologic, hepatic, renal, endocrine, cardiovascular, gastrointestinal (other than UC), pulmonary or metabolic disease.

• History of tuberculosis (TB) infection.

• Treatment with systemic corticosteroids within 1 week prior to randomization.

• Treatment with TNF-a inhibitors or other biologics within 2 months prior to randomization.

• Treatment with immunosuppressants, initiated or changed within 3 months prior to randomization .

• Current use of probiotic or prebiotic preparations

• Regular daily use of NSAIDs, within 7 days prior to randomization.

• Administration of any experimental therapy within 90 days or 5x the half-life.

• History of drug or alcohol abuse.

• Pregnant or lactating women.

• Medical, psychiatric, cognitive, or other conditions that compromise the subject's ability to complete the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• GLPG0974
1 capsule in the morning and 1 capsule in the evening with food during 28 days
• Placebo
1 capsule in the morning and 1 capsule in the evening with food during 28 days

Locations

Country	Name	City	State
Belgium	Imelda	Bonheiden
Belgium	UZ Gent	Gent
Belgium	AZ Groeninge	Kortrijk
Belgium	UZ Leuven	Leuven
Czech Republic	Hepato-Gastroenterologie HK, s.r.o.	Hradec Kralove
Czech Republic	Fakulní nemocnice Olomouc	Olomouc
Czech Republic	Homolka Hospitál	Prague
Czech Republic	Nemocnice Slaný	Slany
Czech Republic	Krajská zdravotní a.s., Masarykova nemocnice v Ústí nad Labem T. Bati a.s.	Usti nad Labem
Czech Republic	Krajská nemocnice Tomáše Bati - Zlin	Zlin
Czech Republic	Nemocnice Znojmo	Znojmo
Latvia	Latvijas Juras Medicinas Centrs	Riga
Latvia	Rigas slimnica Bikor Holim	Riga
Latvia	SIA Gremošanas slimibu centrs "Gastro"	Riga
Slovakia	Univerzitná nemocnica Bratislava	Bratislava
Slovakia	Fakultná Nemocnica Nitra	Nitra

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

Belgium,  Czech Republic,  Latvia,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse events	To evaluate the safety and tolerability of GLPG0974 in terms of the number of adverse events reported	Screening up to Follow up (14 days after last dosing)	Yes
Primary	Changes in physical exam measures	To evaluate the safety and tolerability of GLPG0974 in terms of the changes in physical exam measures reported	Screening up to Follow up (14 days after last dosing)	Yes
Primary	Changes in vital signs as measured by heart rate, blood pressure and oral temperature	To evaluate the safety and tolerability of GLPG0974 in terms of the changes in vital signs as measured by heart rate, blood pressure and oral temperature reported	Screening up to Follow up (14 days after last dosing)	Yes
Primary	Changes in 12-lead ECG measures	To evaluate the safety and tolerability of GLPG0974 in terms of the changes in 12-lead ECG measures reported	Screening up to Follow up (14 days after last dosing)	Yes
Primary	Changes in blood safety lab parameters	To evaluate the safety and tolerability of GLPG0974 in terms of changes in blood safety lab parameters reported	Screening up to Follow up (14 days after last dosing)	Yes
Primary	Changes in urine safety lab parameters	To evaluate the safety and tolerability of GLPG0974 in terms of changes in urine safety lab parameters reported	Screening up to Follow up (14 days after last dosing)	Yes
Secondary	Changes in (partial) Mayo clinical disease activity score	To evaluate the efficacy of GLPG0974 in terms of changes in (partial) Mayo clinical disease activity score reported	From Day 1 to Day 29	No
Secondary	Changes in histopathological clinical activity score in colon biopsies	To evaluate the efficacy of GLPG0974 in terms of changes in histopathological clinical activity score (Geboes score) in colon biopsies reported	Day 1 and Day 29	No
Secondary	The amount of GLPG0974 in plasma over time after multiple oral doses of GLPG0974	To evaluate the amount of GLPG0974 in plasma over time after multiple oral doses of GLPG0974 - pharmacokinetics (PK) in ulcerative colitis patients	Day 8, Day 15 and Day 29	No
Secondary	Changes in the levels of faecal calprotectin over time after multiple oral doses of GLPG0974	To evaluate the changes in the levels of calprotectin in faeces over time after multiple oral doses of GLPG0974 - pharmacodynamics (PD) in ulcerative colitis patients	Screening up to Day 29	No
Secondary	Changes in the levels of C-reactive protein in serum over time after multiple oral doses of GLPG0974	To evaluate the changes in the levels of C-reactive protein in serum over time after multiple oral doses of GLPG0974 - pharmacodynamics (PD) in ulcerative colitis patients	Screening up to Day 29	No
Secondary	Changes in the levels of myeloperoxidase (MPO) in colon biopsies over time after multiple oral doses of GLPG0974	To evaluate the changes in the levels of MPO in colon biopsies over time after multiple oral doses of GLPG0974 - pharmacodynamics (PD) in ulcerative colitis patients	Day 1 and Day 29	No
Secondary	Changes in the levels of predominant microbiota in faeces over time after multiple oral doses of GLPG0974	To evaluate the changes in the levels of predominant microbiota in faeces over time after multiple oral doses of GLPG0974 - pharmacodynamics (PD) in ulcerative colitis patients	Day 1 and Day 29	No
Secondary	Changes in the levels of predominant microbiota in colon biopsies over time after multiple oral doses of GLPG0974	To evaluate the changes in the levels of predominant microbiota in colon biopsies over time after multiple oral doses of GLPG0974 - pharmacodynamics (PD) in ulcerative colitis patients	Day 1 and Day 29	No