Drug-Drug Interaction Study: ASP2151 and Montelukast

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02321748
• Other study ID #: M522101-EU23
• Status: Completed
• Phase: Phase 1
• Start date: December 2014
• Est. completion date: April 2015

Study information

• Verified date: February 2019
• Source: Maruho Europe Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Montelukast

• ASP2151

Locations

Country	Name	City	State
United Kingdom	Hammersmith Medicines Research Ltd	London

Sponsors (1)

Lead Sponsor	Collaborator
Maruho Europe Limited

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Peak Plasma Concentration (Cmax) of Methyl Hydroxymontelukast		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
Other	Time of Peak Concentration (Tmax) of Methyl Hydroxymontelukast		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
Other	Area Under the Curve (AUC) of Methyl Hydroxymontelukast		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
Other	Half-Life (t1/2) of Methyl Hydroxymontelukast		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
Other	Peak Plasma Concentration (Cmax) of ASP2151		Blood samples were taken at pre-dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24h after post doses in first or second intervention
Other	Time of Peak Concentration (Tmax) of ASP2151		Blood samples were taken at pre-dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24h after post doses in first or second intervention
Other	Area Under the Curve (AUC) of ASP2151		Blood samples were taken at pre-dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24h after post doses in first or second intervention
Other	Half-Life (t1/2) of ASP2151		Blood samples were taken at pre-dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24h after post doses in first or second intervention
Other	Apparent Volume of Distribution (Vd/f) of ASP2151		Blood samples were taken at pre-dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24h after post doses in first or second intervention
Other	Apparent Total Body Clearance (CL/f) of ASP2151		Blood samples were taken at pre-dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24h after post doses in first or second intervention
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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