Drug-Drug Interaction Study: ASP2151 and Midazolam

NCT02403635 | Completed Phase 1 Results

• 1 other identifier: M522101-EU24
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Keywords

HSV; Herpes; volunteers; drug-drug interaction

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) 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

• 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 Outcomes (1)

• Number of Participants With Serious and Non-Serious Adverse Events

  Up to 32 days after the last dose

Other Outcomes (15)

• 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

• 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

• 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

Study Arms (1)

Midazolam + ASP2151

OTHER

400 mg ASP2151 followed by 7.5 mg midazolam

Drug: Midazolam; Drug: ASP2151

Interventions

Midazolam DRUG

Also known as: Midazolam-ratiopharm

Midazolam + ASP2151

ASP2151 DRUG

Midazolam + ASP2151

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maruho Europe Limited: lead

Study Sites (1)

Hammersmith Medicines Research Ltd

London, NW10 7EW, United Kingdom

Location

MeSH Terms

Conditions

Herpes Simplex

Interventions

Midazolam; ASP2151

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Maruho Co.,Ltd. Kyoto R&D Center
• Organization: Clinical Development Dept.

ctinfo@mii.maruho.co.jp

+81-75-325-3255

Study Officials

• Joachim Dr Kempeni

  Maruho Europe Ltd

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2015
• First Posted: March 31, 2015
• Study Start: April 1, 2015
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: February 21, 2019
• Results First Posted: January 14, 2019

Record last verified: 2019-01

Locations

GB (1)