Drug Drug Interaction
Conditions
Brief summary
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
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.
Interventions
DRUGSyB V-1901
SyB V-1901 10 mg via IV infusion for 2 hours
DRUGCyclosporine
200 mg Capsule
Sponsors
SymBio Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration versus time curve (AUC) of BCV | From initiation of SyB V-1901 administration though 16 days |
| Maximum Plasma Concentration (Cmax) of brincidofovir (BCV) | From initiation of SyB V-1901 administration though 16 days |
Secondary
| Measure | Time frame |
|---|---|
| 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 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 |
| Number of subjects with adverse events (AE) | Follow up 22 days post dose |
| Cmax of cidofovir (CDV) | From initiation of SyB V-1901 administration though 16 days |
Other
| Measure | Time frame |
|---|---|
| Genotype of CYP4F2 | Pre-Day1 |
| Genotype of OATP1B1 | Pre-Day1 |
Countries
Japan
Outcome results
None listed