Pharmacokinetics of Besifovir in Adults With Normal and Impaired Renal Function

A Non-randomized, Open, Single-dose, Parallel Designed Clinical Study to Evaluate Safety and Pharmacokinetic Characteristics After Oral Administration of Besivo® in Patients With Renal Impairment and Healthy Adult Volunteers

This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of Besifovir and its metabolite, LB80331, in participants with normal and impaired renal function

Study Overview

• Status: Unknown
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: Besifovir Dipivoxil Maleate

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kim Min Jung; Phone Number: 8225263179; Email: mjkim90@ildong.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All Individuals:

1. Have no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including vital signs, 12-lead electrocardiogram (ECG), or clinical laboratory tests.
2. Patients who were explained about the purpose, methods and effects of the clinical trial and then, signed a written consent form

Individuals with mild, moderate, or severe renal impairment must also meet the following additional inclusion criteria to be eligible for participation in this study:

1. Age of 19 to 65 years at the time of the screening visit.
2. A person whose body mass index (BMI) is greater than 18 kg/m^2 and less than 27 kg/m^2 at the time of the screening visit.

3. Individuals with severe renal impairment, estimated Glomerular Filtration Rate (eGFR) must be 15-29 mL/min/1.73m^2 (using the Modification of Diet in Renal Disease (MDRD) method) at the time of the screening visit.

   Individuals with moderate renal impairment, eGFR must be 30-59 mL/min/1.73m^2 (using the MDRD method) at the time of the screening visit.

   Individuals with mild renal impairment, eGFR must be 60-89 mL/min/1.73m^2 (using the MDRD method) at the time of the screening visit.

4. Stable renal impairment with no clinically significant changes within 3 months prior to the screening visit.

Individuals with normal renal function must also meet the following additional inclusion criteria to be eligible for participation in this study:

1. A healthy adult who is at least 19 years old at the time of the screening visit.
2. A person whose BMI is greater than 18 kg/m^2 and less than 30 kg/m^2 at the time of the screening visit.

Exclusion Criteria:

1. Medical history

   • Clinically significant cardiovascular, respiratory, renal, gastrointestinal, hepatic, hematologic, neurologic, thyroid or any other medical illness or psychiatric disorder, as determined by the Investigator
   • A person with a history of chronic hepatitis B
   • A person with a history of gastrointestinal disorders (ex. Crohn's disease, ulcerative colitis, etc.) or surgery (except for simple appendectomy or herniotomy) that may affect the absorption of the investigational product.

2. A person who shows the following in the diagnostic test during the screening period.

   • Positive screening test for Hepatitis B Virus surface Antigen (HBs-Ag), human immunodeficiency virus (HIV) test, hepatitis C test, Venereal Disease Research Laboratory (VDRL) test
   • Clinically significant abnormal ECG findings.
   • Aspartate aminotransferase (AST) and aminotransferase (ALT) values exceed the upper limit of normal range (ULN) by more than 2 times.
   • Total Bilirubin, Gamma-Glutamyl Transpeptidase (γ-GTP) > 1.5 X ULN, Creatine Phosphokinase (CK) > 2 X ULN
   • Clinically significant laboratory abnormalities or abnormalities which are deemed to interfere with the ability to interpret study data.
3. A person who has a history of drug abuse or whose urine drug screening test result during the screening period came back positive for abusive drug use.

4. The contraindication of comedication drugs and diets

   • A person who has been administered with the investigational product or a bioequivalence study drug in another clinical trial within 180 days of the screening visit.

5. Other criteria

   • A woman whose urine human chorionic gonadotropin (hCG) test results were positive and who is pregnant or breastfeeding.
   • A person who has donated partial or full amount of blood within 60 days of the screening visit, who has given blood through apheresis within 28 days, or who has been transfused within 28 days.
   • History of regular alcohol intake > 21 units per week of alcohol before 28 dyas or unwilling to abstain from alcohol for study period before the start of admission until the final Completion Visit assessments.
   • A person who has smoked excessively within 28 days of the screening visit or whose (> 10 cigarettes/day) or◦ who can't quit smoking during the trial
   • Consumption of caffeine products within 28 days (caffeine drink > 7 glass/day) who can't abstain from caffeine products during the trial
   • Consumption of any grapefruit juice within 48 hours before administration of investigational product or subjects who can't abstain from grapefruit juice during the trial
   • Fertile subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 2 weeks after the administration of investigational product.
   • Unwillingness or inability to follow the procedures outlined in the protocol.
   • 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: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy Subjects	Drug: Besifovir Dipivoxil Maleate; Besifovir 150 mg q.d.
Experimental: Mild Renal Impairment (RI)	Drug: Besifovir Dipivoxil Maleate; Besifovir 150 mg q.d.
Experimental: Moderate RI	Drug: Besifovir Dipivoxil Maleate; Besifovir 150 mg q.d.
Experimental: Severe RI	Drug: Besifovir Dipivoxil Maleate; Besifovir 150 mg q.d.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetics (PK) profiles of LB80331: Area under the plasma concentration-time curve (AUC)_0-t	This endpoint will measure the plasma PK profiles of LB80331. PK parameters that will be measured include AUC_0-t	Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hours
Plasma pharmacokinetics (PK) profiles of LB80331: Cmax	This endpoint will measure the plasma PK profiles of LB80331. PK parameters that will be measured include Cmax	Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile of Besifovir as measured by incidence of adverse events and laboratory abnormalities	Review of adverse events and safety labs	Up to 16 days

Collaborators and Investigators

• Sponsor: IlDong Pharmaceutical Co Ltd

Study record dates

Study Major Dates

• Study Start (Anticipated): February 13, 2020
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: January 28, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Actual): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 29, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Maleic acid
• Other Study ID Numbers: ID-BVCL-103

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