Clinical trial NCT04542252: Drug-Drug Interaction Study of Intravenous Administration of SyB V-1901 and Cyclosporine in Japanese Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Drug Interaction
Lead sponsor: SymBio Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-09-09
Enrollment: 13
Sex: MALE
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of brincidofovir (BCV)
timeFrame: From initiation of SyB V-1901 administration though 16 days
measure: Area under the plasma concentration versus time curve (AUC) of BCV
timeFrame: From initiation of SyB V-1901 administration though 16 days
Secondary outcomes:
measure: Cmax of cidofovir (CDV)
timeFrame: From initiation of SyB V-1901 administration though 16 days
measure: AUC of CDV
timeFrame: From initiation of SyB V-1901 administration though 16 days
measure: Cmax of Intercellular Cidofovir diphosphate (CDV-PP) in Peripheral Blood Mononuclear Cells (PBMCs)
timeFrame: From initiation of SyB V-1901 administration though 18 days
measure: AUC of Intercellular CDV-PP in PBMCs
timeFrame: From initiation of SyB V-1901 administration though 18 days
measure: Cmax of cyclosporine in blood
timeFrame: From initiation of cyclosporine administration though 16 days
measure: AUC of cyclosporine in blood
timeFrame: From initiation of cyclosporine administration though 16 days
measure: Number of subjects with adverse events (AE)
timeFrame: Follow up 22 days post dose
measure: Number of subjects with severity of AEs
timeFrame: Follow up 22 days post dose
measure: Number of subjects with abnormal findings for laboratory parameters
timeFrame: Follow up 22 days post dose
measure: Number of subjects with abnormal findings for blood pressure
timeFrame: Follow up 22 days post dose
measure: Number of subjects with abnormal findings for respiratory rate
timeFrame: Follow up 22 days post dose
measure: Number of subjects with abnormal findings for heart rate
timeFrame: Follow up 22 days post dose
measure: Number of subjects with abnormal findings for temperature
timeFrame: Follow up 22 days post dose
Other outcomes:
measure: Genotype of CYP4F2
timeFrame: Pre-Day1
measure: Genotype of OATP1B1
timeFrame: Pre-Day1
Locations:
city: Hachioji-shi
country: Japan
facility: Research Site
state: Tokyo
Study officials:
affiliation: SymBio Pharmaceuticals
name: Takeshi Yoshida
role: STUDY_DIRECTOR
References: