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

Sponsor
SymBio Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT04542252
Collaborator
(none)
13
1
2
2.7
4.9

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
13 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
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
Actual Study Start Date :
Nov 9, 2020
Actual Primary Completion Date :
Dec 22, 2020
Actual Study Completion Date :
Jan 29, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Maximum Plasma Concentration (Cmax) of brincidofovir (BCV) [From initiation of SyB V-1901 administration though 16 days]

  2. Area under the plasma concentration versus time curve (AUC) of BCV [From initiation of SyB V-1901 administration though 16 days]

Secondary Outcome Measures

  1. Cmax of cidofovir (CDV) [From initiation of SyB V-1901 administration though 16 days]

  2. AUC of CDV [From initiation of SyB V-1901 administration though 16 days]

  3. Cmax of Intercellular Cidofovir diphosphate (CDV-PP) in Peripheral Blood Mononuclear Cells (PBMCs) [From initiation of SyB V-1901 administration though 18 days]

  4. AUC of Intercellular CDV-PP in PBMCs [From initiation of SyB V-1901 administration though 18 days]

  5. Cmax of cyclosporine in blood [From initiation of cyclosporine administration though 16 days]

  6. AUC of cyclosporine in blood [From initiation of cyclosporine administration though 16 days]

  7. Number of subjects with adverse events (AE) [Follow up 22 days post dose]

  8. Number of subjects with severity of AEs [Follow up 22 days post dose]

  9. Number of subjects with abnormal findings for laboratory parameters [Follow up 22 days post dose]

  10. Number of subjects with abnormal findings for blood pressure [Follow up 22 days post dose]

  11. Number of subjects with abnormal findings for respiratory rate [Follow up 22 days post dose]

  12. Number of subjects with abnormal findings for heart rate [Follow up 22 days post dose]

  13. Number of subjects with abnormal findings for temperature [Follow up 22 days post dose]

Other Outcome Measures

  1. Genotype of CYP4F2 [Pre-Day1]

  2. Genotype of OATP1B1 [Pre-Day1]

Eligibility Criteria

Criteria

Ages Eligible for Study:
20 Years to 55 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
Yes
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Hachioji-shi Tokyo Japan

Sponsors and Collaborators

  • SymBio Pharmaceuticals

Investigators

  • Study Director: Takeshi Yoshida, SymBio Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
SymBio Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT04542252
Other Study ID Numbers:
  • BCV-HV01
First Posted:
Sep 9, 2020
Last Update Posted:
Apr 27, 2021
Last Verified:
Apr 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 27, 2021