A Phase I, Open-Label, Randomized, Drug-Drug Interaction Study to Evaluate the Effect of Itraconazole and Voriconazole on the Single-Dose Pharmacokinetics of GLPG1690 in Healthy Male Subjects

A Study in Healthy Male Volunteers to Look at How the Test Medicine GLPG1690 is Taken up by the Body When Doses of Itraconazole and Voriconazole Are Given to Healthy Volunteers

Sponsors

Lead sponsor: Galapagos NV

Source Galapagos NV
Brief Summary

The sponsor wants to investigate how well the test medicine is taken up by the body when given alongside two other already approved medicines. This kind of study is known as a drug-drug interaction study. In this case the other medicines are itraconazole and voriconazole.

The sponsor will also look at the safety and tolerability of the test medicine when taken alone, and when taken with the approved medicines.

Overall Status Completed
Start Date March 16, 2018
Completion Date June 1, 2018
Primary Completion Date June 1, 2018
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Maximum observed plasma concentration of GLPG1690 (Cmax). At various time points between Day 1 pre-dose and Day 5
Area under the plasma concentration-time curve from time zero to infinity of GLPG1690 (AUC0-∞). At various time points between Day 1 pre-dose and Day 5
Apparent terminal half-life of GLPG1690 (t1/2,λz). At various time points between Day 1 pre-dose and Day 5
Secondary Outcome
Measure Time Frame
Number of incidents of TEAEs. Between screening and 10 days after the last dose
Enrollment 18
Condition
Intervention

Intervention type: Drug

Intervention name: GLPG1690

Description: A single oral dose of GLPG1690.

Intervention type: Drug

Intervention name: Itraconazole

Description: A single oral dose of itraconazole.

Arm group label: Treatment B

Intervention type: Drug

Intervention name: Voriconazole

Description: A single oral dose of voriconazole.

Arm group label: Treatment C

Eligibility

Criteria:

Inclusion Criteria:

- Written, signed and dated informed consent form (ICF) as approved by the Independent Ethics Committee (IEC), prior to any screening evaluations.

- Male subject between 18-55 years of age (extremes included) on the day of signing the ICF.

- Body mass index (BMI) between 18.0-32.0 kg/m², inclusive, with body weight at least 50 kg.

- Judged by the investigator to be in good health based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory results.

- Non-smoker, defined as an individual who has abstained from smoking (or the use of e-cigarettes or nicotine containing products) from at least 1 year prior to screening. A breath carbon monoxide reading of less than or equal to 10 ppm at screening and admission.

- Negative urine drug screen (at a minimum: amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, opiates, methadone, and tricyclic antidepressants) and alcohol breath test at screening and admission.

- Negative serology for human immunodeficiency virus (HIV) type 1 or 2, hepatitis B virus surface antigen (HBs-Ag) or hepatitis C virus antibody (HCV-Ab), or any history of hepatitis from any cause, with the exception of hepatitis A at screening.

- Subject must agree to use highly effective contraceptive measures as and must be able and willing to comply with the other prohibitions and restrictions as described in the protocol.

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 study drug or the excipients.

- Use of strong inhibitors and/or inducers of CYP3A4/5 and/or P-gp, including consumption of herbal medications (e.g. St. John's Wort) and grapefruit/grapefruit products within 7 days prior to the first study drug administration.

- Contra-indication for the use of itraconazole or voriconazole as described in the package insert.

- Abnormal liver function test, defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin and/or gamma-glutamyl transferase (GGT) > 1.5 x upper limit of normal (ULN). Retesting is allowed once. Subjects with documented Gilbert's syndrome are eligible for inclusion in the study.

- History of malignancy within the past 5 years (except for basal cell carcinoma of the skin that has been treated with no evidence of recurrence).

- Clinically relevant abnormalities detected on ECG regarding either rhythm, rate or conduction (e.g. QT interval corrected for the heart rate using Fridericia's formula [QTcF] ≥450 ms, or a known long QT syndrome). A first degree heart block or sinus arrhythmia is not considered as a significant abnormality.

- Clinically relevant abnormal vital signs and/or abnormalities detected during physical examination.

- Per judgment of the investigator, substantial blood loss (including blood donation), or a transfusion of any blood product within 8 weeks prior to the first study drug administration.

- Any condition or circumstances that, in the opinion of the investigator, could make a subject unlikely or unable to complete the study or comply with study procedures and requirements.

Gender: Male

Gender based: Yes

Minimum age: 18 Years

Maximum age: 55 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Christopher Brearley, BM, MRCP, MFPM Study Director Galapagos NV
Location
facility Quotient Sciences Limited
Location Countries

United Kingdom

Verification Date

June 2018

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Number Of Arms 3
Arm Group

Arm group label: Treatment A

Arm group type: Experimental

Description: single dose GLPG1690.

Arm group label: Treatment B

Arm group type: Experimental

Description: Single dose itraconazole + single dose GLPG1690.

Arm group label: Treatment C

Arm group type: Experimental

Description: Single dose voriconazole + single dose GLPG1690.

Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov