Drug-Drug Interaction Study: ASP2151 and Montelukast

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Montelukast
* Drug: ASP2151


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Montelukast<br>10mg montelukast alone followed by 10mg montelukast + 400mg ASP2151 | Drug: Montelukast<br> <br> * Other names: SINGULAIR;Drug: ASP2151<br> <br> |
| Other: ASP2151<br>10mg montelukast + 400mg ASP2151 followed by 10mg montelukast alone | Drug: Montelukast<br> <br> * Other names: SINGULAIR;Drug: ASP2151<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of Montelukast |  | Blood samples were taken at pre-dose of Day 1 and 0.5, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48 and 72h after post doses in first or second intervention | 
| Time of Peak Concentration (Tmax) of Montelukast |  | Blood samples were taken at pre-dose of Day 1 and 0.5, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48 and 72h after post doses in first or second intervention | 
| Area Under the Curve (AUC) of Montelukast |  | Blood samples were taken at pre-dose of Day 1 and 0.5, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48 and 72h after post doses in first or second intervention | 
| Half-Life (t1/2) of Montelukast |  | Blood samples were taken at pre-dose of Day 1 and 0.5, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48 and 72h after post doses in first or second intervention | 
| Apparent Volume of Distribution (Vd/f) of Montelukast |  | Blood samples were taken at pre-dose of Day 1 and 0.5, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48 and 72h after post doses in first or second intervention | 
| Apparent Total Body Clearance (CL/f) of Montelukast |  | Blood samples were taken at pre-dose of Day 1 and 0.5, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 48 and 72h after post doses in first or second intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious and Non-Serious Adverse Events | Refer to the result of adverse event. | Up to 32 days after the last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSV, Herpes, volunteers, drug-drug interaction