Drug-Drug Interaction Study: ASP2151 and Ciclosporin

Study Overview
=================
Brief Summary
-----------------
ASP2151 is an experimental treatment for herpes. Patients undergoing organ and tissue transplantation may be prescribed ciclosporin to suppress their immune system to give the transplant an increased chance of not being rejected. A patient with a compromised immune system is more susceptible to infections such as herpes, which will require treatment.

Official Title
-----------------
A Single-centre, Open-label, Randomised, Cross-over, Drug-drug Interaction Study to Investigate the Effect of Repeated Oral Doses of Ciclosporin on the Single-dose Pharmacokinetics of nASP2151 in Healthy Mean

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: ASP2151 400mg + 100mg ciclosporin
* Drug: ASP2151 1200mg + 100mg ciclosporin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A body mass index (Quetelet index) in the range 18.0-30.9 kg/m2. 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 (TOPS). 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), alkaline phosphatase (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. Receipt of a live vaccine in the 3 months before the first dose of study medication, or planned immunisation with a live vaccine during the study. Evidence of any significant bacterial, viral, fungal or parasitic infection during the 4 weeks before dosing (minor fungal nail infections will not be regarded as significant); minor infection (eg common cold) not requiring anti-infective treatment during the 2 weeks before dosing. 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). See Appendix 1 for common CYP3A4 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. 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 5 cigarettes daily. Evidence of drug abuse on urine testing. Positive test for hepatitis B antigen (HBsAg); or positive test for hepatitis B core antibody (HBcAb). Positive test for hepatitis C, HIV1, HIV2, or active and latent tuberculosis. 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. Possibility that the volunteer will not cooperate with the requirements of the protocol. Objection by General Practitioner (GP) to volunteer entering trial.

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

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ASP2151 400mg<br>ASP2151 400mg + 100mg ciclosporin | Drug: ASP2151 400mg + 100mg ciclosporin<br> <br> |
| Other: ASP2151 1200mg<br>ASP2151 1200mg + 100mg ciclosporin | Drug: ASP2151 1200mg + 100mg ciclosporin<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of ASP2151 |  | prior to initial dose on Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after ASP2151 dosing on Day 1 and Day 7, and also 72 h after ASP2151 dosing on Day 7. | 
| Time of Peak Concentration (Tmax) of ASP2151 |  | prior to initial dose on Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after ASP2151 dosing on Day 1 and Day 7, and also 72 h after ASP2151 dosing on Day 7. | 
| Area Under the Curve (AUC) of ASP2151 |  | prior to initial dose on Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after ASP2151 dosing on Day 1 and Day 7, and also 72 h after ASP2151 dosing on Day 7. | 
| Half-Life (t1/2) of ASP2151 |  | prior to initial dose on Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after ASP2151 dosing on Day 1 and Day 7, and also 72 h after ASP2151 dosing on Day 7. | 
| Apparent Total Body Clearance (CL/F) of ASP2151 From Plasma |  | prior to initial dose on Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after ASP2151 dosing on Day 1 and Day 7, and also 72 h after ASP2151 dosing on Day 7. | 
| Apparent Volume of Distribution (Vd/F) of ASP2151 |  | prior to initial dose on Day 1 and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after ASP2151 dosing on Day 1 and Day 7, and also 72 h after ASP2151 dosing on Day 7. | 

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 after the Day 7 dose of ASP2151 | 

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