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

Drug Drug Interaction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04542252
• Other study ID #: BCV-HV01
• Status: Completed
• Phase: Phase 1
• Start date: November 9, 2020
• Est. completion date: January 29, 2021

Study information

• Verified date: April 2021
• Source: SymBio Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: January 29, 2021
• Est. primary completion date: December 22, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Drug Interaction

Intervention

Drug:
• SyB V-1901
SyB V-1901 10 mg via IV infusion for 2 hours
• Cyclosporine
200 mg Capsule

Locations

Country	Name	City	State
Japan	Research Site	Hachioji-shi	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
SymBio Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Genotype of CYP4F2		Pre-Day1
Other	Genotype of OATP1B1		Pre-Day1
Primary	Maximum Plasma Concentration (Cmax) of brincidofovir (BCV)		From initiation of SyB V-1901 administration though 16 days
Primary	Area under the plasma concentration versus time curve (AUC) of BCV		From initiation of SyB V-1901 administration though 16 days
Secondary	Cmax of cidofovir (CDV)		From initiation of SyB V-1901 administration though 16 days
Secondary	AUC of CDV		From initiation of SyB V-1901 administration though 16 days
Secondary	Cmax of Intercellular Cidofovir diphosphate (CDV-PP) in Peripheral Blood Mononuclear Cells (PBMCs)		From initiation of SyB V-1901 administration though 18 days
Secondary	AUC of Intercellular CDV-PP in PBMCs		From initiation of SyB V-1901 administration though 18 days
Secondary	Cmax of cyclosporine in blood		From initiation of cyclosporine administration though 16 days
Secondary	AUC of cyclosporine in blood		From initiation of cyclosporine administration though 16 days
Secondary	Number of subjects with adverse events (AE)		Follow up 22 days post dose
Secondary	Number of subjects with severity of AEs		Follow up 22 days post dose
Secondary	Number of subjects with abnormal findings for laboratory parameters		Follow up 22 days post dose
Secondary	Number of subjects with abnormal findings for blood pressure		Follow up 22 days post dose
Secondary	Number of subjects with abnormal findings for respiratory rate		Follow up 22 days post dose
Secondary	Number of subjects with abnormal findings for heart rate		Follow up 22 days post dose
Secondary	Number of subjects with abnormal findings for temperature		Follow up 22 days post dose