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

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

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

Study Overview

• Status: Completed
• Conditions: Drug Drug Interaction
• Intervention / Treatment: Drug: SyB V-1901; Drug: Cyclosporine

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Hachioji-shi, Tokyo, Japan
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; 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; SyB V-1901 10 mg via IV infusion for 2 hours; Drug: Cyclosporine; 200 mg Capsule
Experimental: Group 2; 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; SyB V-1901 10 mg via IV infusion for 2 hours; Drug: Cyclosporine; 200 mg Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Time Frame
Genotype of CYP4F2	Pre-Day1
Genotype of OATP1B1	Pre-Day1

Collaborators and Investigators

• Sponsor: SymBio Pharmaceuticals
• Investigators: Study Director: Takeshi Yoshida, SymBio Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2020
• Primary Completion (Actual): December 22, 2020
• Study Completion (Actual): January 29, 2021

Study Registration Dates

• First Submitted: August 29, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 25, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: BCV-HV01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No