A Food Effect Study of Besifovir in Healthy Subjects

An Open Label, Randomized, 2-sequence, 2-period, Single-dose Cross-over Design Clinical Trial to Evaluate the Food Effect on Pharmacokinetics of BESIVO in Healthy Adult Volunteers

To investigate the PK characteristics and the effect of food on the PK in healthy volunteers who receive Besifovir dipivoxil in fed versus fasted condition

Study Overview

• Status: Completed
• Conditions: Food Effect; Health Subjects
• Intervention / Treatment: Drug: Besifovir dipivoxil

Detailed Description

A randomized, open-label, 2-sequence, 2-period, single-dose cross-over clinical trial to investigate the pharmacokinetics incorporating a comparison of fed/fasted pharmacokinetics of Besifovir dipivoxil in healthy volunteers

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Inje University Busan Paik Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject who has the ability to comprehend the study objectives, contents and the property of the study drug before participating in the trial
2. Age of 19 to 50 years and Body Mass Index [BMI] of 18.0 to 27.0 kg/m2
3. Subject with no congenital or chronic disease and no medically symptomatic findings
4. Subject must be healthy on the basis of vital signs, 12-lead ECG, physical examination and laboratory test performed at screening.

Exclusion Criteria:

1. Medical history

   • History of clinically significant of gastrointestinal system, hepatic portal system, cardiovascular system, respiratory system, endocrine system, renal-urinary system, immunologic system, musculoskeletal system, neurological, or psychiatric system, blood tumor, ophthalmology, otolaryngology disorder(as determined by the Investigator).
   • Prior history of a gastrointestinal disorder that may affect drug absorption, distribution, metabolism and elimination (e.g., Crohn's disease, ulcer or surgery, except for simple appendectomy or hernia surgery)

2. Clinical tests

   • Systolic Blood Pressure: lower than 90mmHg or higher than 140mmHg, Diastolic Blood Pressure: lower than 60mmHg or higher than 180mmHg

   • Repeated measurement of laboratory value outside the reference range that the investigator considers to be of clinical relevance

     1. Aspartate transaminase [AST] or alanine aminotransferase [ALT] > 1.5 x upper limit of normal range
     2. Total bilirubin > 1.5 x upper limit of normal range
     3. estimated glomerular filtration rate [eGFR] < 75mL/min/1.73m2 (using Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equations)
     4. Positive screening on Hepatitis B surface antigen(HBsAg), anti-Hepatitis C virus(HCV), anti-Human immunodeficiency virus(HIV) or Syphilis reagin test
   • Subjects with clinically significant abnormalities in 12-lead ECG determined by repeated measurement

3. Allergy, hypersensitivity, and drug abuse

   • History of significant hypersensitivity to Besifovir, this drug ingredient or other drug (e.g., aspirin, antibiotics)
   • History of clinically significant allergy/hypersensitivity
   • A history of drug abuse (especially, central nervous system agents such as sleeping pills, central painkillers, opiates or psychotropic drugs) or the presence of positive reactions to drugs that have abuse potential in urine screenings for drugs(amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines)

4. The contraindication of comedication drugs and diets

   • Subject who has taken drugs for drug metabolizing enzyme induction and inhibition within 1 month before the first adminstration
   • Subject who has taken other ethical the count [ETC] drugs (including prescription of herbal medicine) within the last 14 days, or over the count [OTC] drugs within the last 10 days (as determined by the Investigators)
   • Subject who has taken abnormal meals (eg. ingestion of grapefruit juice, garlic extract, broccoli, and kale) which can affect to drug absorption, distribution, metabolism, and excretion [ADME] and supplements within 7 days prior to administration of trial medication and during the trial
   • Subject who has participated in any other bioequivalence study or clinical trial and taken other investigational products within 3 months prior to the first adminstration

5. Donation and receipt of blood

   • Subject who had whole blood donation within 2 months prior to administration of trial medication
   • Subject who had component blood donation or transfusion within 1 months prior to administration of trial medication

6. Pregnant and contraception

   • Pregnant, positive of pregnancy test or breast-feeding women

   • Subjects who do not use medically acceptable contraception during the entire period of the trial

     1. Use of intrauterine device
     2. Use of intercourse contraceptive (male or female) and spermicide
     3. Vasectomy
     4. Tubectomy, canal ligation and hysterectomy

7. Other criteria

   • Use of Xanthine (eg. green tea, coffee, black tea, coke, cocoa, chocolate, energy drink, and etc.) within 3 days prior to administration of trial medication and during the trial
   • Intake of more than 30g of alcohol per day or who can't abstain from alcohol during the trial
   • Subjects who can't quit smoking during the trial
   • Subjects who are considered to be unacceptable in this study under the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A-fasted dosing followed by fed dosing; Fasted dosing of Besifovir dipivoxil followed by fed dosing; Dosing in the fasted state followed by fed dosing	Drug: Besifovir dipivoxil; 150mg Besifovir dipivoxil, single dose, oral; Other Names: Besivo tab
Experimental: B-fed dosing followed by fasted dosing; Fed dosing of Besifovir dipivoxil followed by fasted dosing; Dosing in the fed state followed by fasted dosing	Drug: Besifovir dipivoxil; 150mg Besifovir dipivoxil, single dose, oral; Other Names: Besivo tab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration [Cmax] of Besifovir	The Cmax is the maximum observed plasma concentration.	Up to 24 Hours after study drug administration
Area Under the Curve [AUC] of of Besifovir	Area under the plasma concentration versus time curve for Besifovir	Up to 24 Hours after study drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Besifovir	Area under the plasma concentration-time curve from time zero to infinite time	Up to 24 Hours after study drug administration
Time to reach the Cmax [Tmax] of Besifovir	Time to reach the Cmax of Besifovir	Up to 24 Hours after study drug administration
Apparent terminal half-life [t1/2]	apparent terminal half-life of Besifovir	Up to 24 Hours after study drug administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Besifovir: incidence of treatment emergent adverse event [TEAE]'s, abnormalities	Safety of Besifovir administered orally will be assessed by incidence of treatment emergent adverse event [TEAE]'s, abnormalities in vital sign assessments, ECG's, clinical laboratory assessments, and physical exams	Up to 14 days after last study drug administration

Collaborators and Investigators

• Sponsor: IlDong Pharmaceutical Co Ltd
• Investigators: Principal Investigator: jong-Lyul GhimK, Inje University

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2019
• Primary Completion (Actual): January 28, 2019
• Study Completion (Actual): February 12, 2019

Study Registration Dates

• First Submitted: March 19, 2019
• First Submitted That Met QC Criteria: March 21, 2019
• First Posted (Actual): March 22, 2019

Study Record Updates

• Last Update Posted (Actual): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 21, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: ID-BVCL-402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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