Drug-Drug Interaction Study: ASP2151 and Ritonavir

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

ASP2151 is an experimental treatment for herpes. HIV infected people are susceptible to contracting other infections because of their compromised immune system. As HIV patients will be taking drugs to treat the virus this study aims to see if ASP2151 would interact with one of the drugs that is commonly prescribed to HIV patients (ritonavir).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ritonavir; Drug: ASP2151

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7EW
    • Hammersmith Medicines Research Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy volunteers
• 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.

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 metabolic pathway (unless judged as not clinical significant by the investigator and sponsor).
• 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.
• Loss of more than 400 mL blood during the 3 months before the trial, eg as a blood donor.
• Presence or history of drug or alcohol abuse, or intake of more than 21 units of alcohol weekly or more than 10 cigarettes daily.
• Evidence of drug abuse on urine testing.
• Positive test for hepatitis B, hepatitis C, HIV1 or HIV2.
• Blood pressure (BP) and heart rate (HR) 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 400mg ASP2151; 400mg ASP2151 alone followed by 400mg ASP2151 + 600mg ritonavir	Drug: ritonavir; Other Names: Norvir; Drug: ASP2151
Other: 1200mg ASP2151; 1200mg ASP2151 alone followed by 1200mg ASP2151 + 600mg ritonavir	Drug: ritonavir; Other Names: Norvir; Drug: ASP2151

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peak Plasma Concentration (Cmax) of ASP2151	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
Time of Peak Concentration (Tmax) of ASP2151	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
Area Under the Curve (AUC) of ASP2151	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
Half-Life (t1/2) of ASP2151	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
Apparent Total Body Clearance (CL/F) of ASP2151 From Plasma	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
Apparent Volume of Distribution (Vd/F) of ASP2151	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 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 31 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax) of ASP1955888-00	ASP1955888-00 is a metabolite of the study drug (ASP2151)	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
Time of Peak Concentration (Tmax) of ASP1955888-00	ASP1955888-00 is a metabolite of the study drug (ASP2151)	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
Area Under the Curve (AUC) of ASP1955888-00	ASP1955888-00 is a metabolite of the study drug (ASP2151)	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
Half-life (t1/2) of ASP1955888-00	ASP1955888-00 is a metabolite of the study drug (ASP2151)	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
Apparent Total Body Clearance (CL/F) From Plasma of ASP1955888-00	ASP1955888-00 is a metabolite of the study drug (ASP2151)	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention
Apparent Volume of Distribution (Vd/F) of ASP1955888-00	ASP1955888-00 is a metabolite of the study drug (ASP2151)	Blood samples were taken at pre-dose of Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72h after post doses in first or second intervention

Collaborators and Investigators

• Sponsor: Maruho Europe Limited

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 15, 2014
• First Submitted That Met QC Criteria: August 20, 2014
• First Posted (Estimate): August 22, 2014

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: HIV; volunteers; drug-drug interaction; HSV; Herpes
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir
• Other Study ID Numbers: M522101-EU22; 2014-002174-37 (EudraCT Number)