Drug-Drug Interaction Study: ASP2151 and Montelukast

A Single-centre, Open-label, Randomised, Crossover, Drug-drug Interaction Study in Healthy Men to Investigate the Effect of a Single Dose of ASP2151 on the Pharmacokinetics of Montelukast

CYP2C8 is involved in the metabolism of many drugs. So, it is important to assess in vivo the inhibitory effect of ASP2151 on that enzyme to determine any possible drug interactions. The aim of this trial is to investigate the potential for interaction of ASP2151 with the CYP2C8 probe substrate montelukast.

Inclusion Criteria:

• A body mass index (Quetelet index) in the range 18.0-30.9.
• Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
• Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate.
• Willingness to give written consent to have data entered into The Overvolunteering Prevention System.

Exclusion Criteria:

• Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
• Any of the following liver function tests higher than 1.5 times the ULN at the screening visit: aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP, bilirubin, gamma glutamyl transpeptidase (gamma-GT).
• Platelet counts outside normal limits.
• Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous.
• Clinically significant impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness.
• History of bleeding diathesis.
• Surgery (eg stomach bypass) or medical condition that might affect absorption of medicines.
• Presence or history of severe adverse reaction to any drug, history of multiple drug allergies (multiple defined as >3), or sensitivity to trial medication.
• Use, during the 28 days before the first dose of trial medication, of any prescription medicine, or any other medicine or herbal remedy (such as St John's wort) known to interfere with the CYP3A4, CYP2C19, CYP2C8 or CYP2C9 metabolic pathway (unless judged as not clinical significant by the investigator and sponsor). See Appendix 1: for common CYP3A4, CYP2C19, CYP2C8 and CYP2C9 interactors/substrates.
• Use, during the 7 days before the first dose of trial medication, of any over the counter medicine, with the exception of paracetamol (acetaminophen).
• Participation in another clinical trial of a new chemical entity or a prescription medicine within the previous 3 months.
• Presence or history of drug or alcohol abuse, or intake of more than 21 units of alcohol weekly or more than 10 cigarettes daily.
• Blood pressure and heart rate in seated position at the screening examination outside the ranges 90-140 mm Hg systolic, 40-90 mm Hg diastolic; heart rate 40_100 beats/min. However, if the investigator deems the result to be not clinically significant the subject may be included.
• Possibility that the volunteer will not cooperate with the requirements of the protocol.
• Evidence of drug abuse on urine testing.
• Positive test for hepatitis B, hepatitis C, HIV1 or HIV2.
• Loss of more than 400 mL blood during the 3 months before the trial, eg as a blood donor.
• Objection by General Practitioner (GP) to volunteer entering trial.