Drug-Drug Interaction Study of Intravenous Administration of SyB V-1901 and Cyclosporine in Japanese Healthy Subjects

Study Overview
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Brief Summary
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To evaluate the effect of coadministered cyclosporine on the pharmacokinetics of brincidofovir following simultaneous administration of SyB V-1901 with cyclosporine, or coadministration of cyclosporine at 2 hours after the completion of SyB V-1901 infusion in healthy adult subjects

Detailed Description
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This study is an open-label, randomized and crossover study designed to evaluate the effect of cyclosporine on the pharmacokinetics of SyB V-1901. Healthy adult subjects will receive an IV dose of SyB V-1901 alone, simultaneous administration of SyB V-1901 with cyclosporine, and coadministration of cyclosporine at 2 hours after completion of SyB V-1901 infusion. Eligible subjects will be randomized to one of two groups, to receive the treatment sequence of assigned group.

Official Title
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An Open-label, Randomized, Crossover Study to Evaluate the Drug Interaction of Coadministered Cyclosporine on the Pharmacokinetics and Safety of Intravenous Administration of SyB V-1901 in Japanese Healthy Subjects

Conditions
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Drug Drug Interaction

Intervention / Treatment
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* Drug: SyB V-1901
* Drug: Cyclosporine


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Healthy adult male aged between 20 to 55 years at informed consent BMI from 18 to 32 kg/m2 with a body weight of ≥ 50 kg Creatinine Clearance ≥ 60 mL/min at screening Judged to be in good general health, based on the review of medical history and the screening and Pre-Day1 examination Main Exclusion Criteria: Positive for HIV antibody, or HBs antigen, or HCV antibody at the screening or within 6 months prior to the start of screening Have a history of infection of SARS-CoV-2, or subjects who have close contact with infected patients of SARS-CoV-2 within 2 weeks prior to screening or visit to epidemic area of SARS-CoV-2 infection in outside of Japan or have close contact with person who visit to epidemic area of SARS-CoV-2 infection within 2 weeks prior to screening Positive for SARS-CoV-2 polymerase chain reaction (PCR) in lower respiratory tract specimens, nasopharyngeal swabs or saliva and so on at screening or have a fever ≥ 37.5 °C and respiratory symptoms Have a history of drug abuse or alcohol dependence within 2 years prior to the start of screening Have a history of gastrointestinal disorders or cholecystectomy etc., which could interfere with the absorption of cyclosporine or could interfere with normal gastrointestinal anatomy or motility, but except for uncomplicated appendectomy. Have a history or symptoms of cardiovascular disease, including but not limited to coronary artery disease, hypertension, congestive heart disease, and clinically significant cardiac disorder. Have a history of hematological disorders or have a risk of gastrointestinal bleeding Have a history of chronic liver disease or hepatic impairment, including but not limited to alcoholic liver disease, chronic viral hepatitis, autoimmune hepatitis, steatosis or hemochromatosis. Have increased Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) greater than ULN at screening or Pre-Day1 History of Gilbert's syndrome or increased total bilirubin greater than 1.5x the upper limit of the normal range at screening or Pre-Day1 Have symptoms of infection within 2 weeks prior to Pre-Day1 Have clinically significant abnormal hemoglobin at the screening or Pre-Day1, or a clinically significant iron deficiency Have a history of blood donation or had clinically significant blood loss within 30 days prior to Day 1, or platelet/plasma donation within 7 days prior to Day 1 Have received any investigational drug, or device within 30 days prior to Day1 History of tobacco- or nicotine-containing product use within 6 months prior to Day1

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>SyB V-1901 alone, Simultaneous administration of SyB V-1901 and cyclosporine, Coadministration of cyclosporine at 2 hours after the completion of SyB V-1901 infusion | Drug: SyB V-1901<br>* SyB V-1901 10 mg via IV infusion for 2 hours<br>Drug: Cyclosporine<br>* 200 mg Capsule<br>|
| Experimental: Group 2<br>Simultaneous administration of SyB V-1901 and cyclosporine, SyB V-1901 alone, Coadministration of cyclosporine at 2 hours after the completion of SyB V-1901 infusion | Drug: SyB V-1901<br>* SyB V-1901 10 mg via IV infusion for 2 hours<br>Drug: Cyclosporine<br>* 200 mg Capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of brincidofovir (BCV) |  | From initiation of SyB V-1901 administration though 16 days | 
| Area under the plasma concentration versus time curve (AUC) of BCV |  | From initiation of SyB V-1901 administration though 16 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of cidofovir (CDV) |  | From initiation of SyB V-1901 administration though 16 days | 
| AUC of CDV |  | From initiation of SyB V-1901 administration though 16 days | 
| Cmax of Intercellular Cidofovir diphosphate (CDV-PP) in Peripheral Blood Mononuclear Cells (PBMCs) |  | From initiation of SyB V-1901 administration though 18 days | 
| AUC of Intercellular CDV-PP in PBMCs |  | From initiation of SyB V-1901 administration though 18 days | 
| Cmax of cyclosporine in blood |  | From initiation of cyclosporine administration though 16 days | 
| AUC of cyclosporine in blood |  | From initiation of cyclosporine administration though 16 days | 
| Number of subjects with adverse events (AE) |  | Follow up 22 days post dose | 
| Number of subjects with severity of AEs |  | Follow up 22 days post dose | 
| Number of subjects with abnormal findings for laboratory parameters |  | Follow up 22 days post dose | 
| Number of subjects with abnormal findings for blood pressure |  | Follow up 22 days post dose | 
| Number of subjects with abnormal findings for respiratory rate |  | Follow up 22 days post dose | 
| Number of subjects with abnormal findings for heart rate |  | Follow up 22 days post dose | 
| Number of subjects with abnormal findings for temperature |  | Follow up 22 days post dose |