Drug-Drug Interaction Study: ASP2151 and Midazolam

Healthy Clinical Trial

Official title:

A Single-centre, Open-label Study in Healthy Men to Investigate the Effect of Repeated Oral Doses of ASP2151 on the Pharmacokinetics of Midazolam in Healthy Men

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02403635
• Other study ID #: M522101-EU24
• Status: Completed
• Phase: Phase 1
• Start date: April 2015
• Est. completion date: May 2015

Study information

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

Clinical Trial Summary

CYP3A4 is involved in the metabolism of many drugs. So, it is important to assess in vivo the induction effect of ASP2151 on that enzyme to determine the extent of any possible drug interactions. The aim of this trial is to investigate the potential for interaction of ASP2151 with the CYP3A4 probe substrate midazolam.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: May 2015
• Est. primary completion date: May 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 (129,000-346,000/µL).

• 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.

• Presence or history of sleep apnoea or myasthenia gravis.

• 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 pathways.

• 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 5 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:
• Midazolam

• 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 1-hydroxymidazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
Other	Time of Peak Concentration (Tmax) of 1-hydroxymidazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
Other	Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of 1-hydroxymidazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
Other	Half-life (t1/2) of 1-hydroxymidazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
Other	Trough Plasma Concentration (Ctrough) of ASP2151		Days 5 to 12
Other	Peak Plasma Concentration (Cmax) of ASP2151		pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12
Other	Time of Peak Concentration (Tmax) of ASP2151		pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12
Other	Area Under Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of ASP2151		pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12
Other	Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-8) of ASP2151		pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12
Other	Half-life (t1/2) of ASP2151		pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12
Other	Apparent Volume of Distribution (Vd/F) of ASP2151		pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12
Other	Apparent Total Body Clearance (CL/F) of ASP2151		pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12
Other	Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Midazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
Other	Apparent Volume of Distribution (Vd/F) of Midazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
Other	Apparent Total Body Clearance (CL/F) of Midazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
Primary	Peak Plasma Concentration (Cmax) of Midazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
Primary	Time of Peak Concentration (Tmax) of Midazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
Primary	Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-8) of Midazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
Primary	Half-life (t1/2) of Midazolam		prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26
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