Study Evaluating the Bioequivalence of Brincidofovir Form H and Form II Tablets in Healthy Adults

Smallpox Clinical Trial

— BCV-001  

Official title:

A Phase 1, Open-label, Single-dose, Randomized, Two-period, Crossover Study Evaluating the Bioequivalence of Brincidofovir Form H and Form II Tablets in Healthy Adult Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05935917
• Other study ID #: EBS-BCV-001
• Status: Completed
• Phase: Phase 1
• Start date: May 30, 2023
• Est. completion date: September 27, 2023

Study information

• Verified date: April 2024
• Source: Emergent BioSolutions
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to evaluate whether both Form H and Form II, 100mg brincidofovir tablets are bioequivalent, when given under fasting conditions in healthy adults.

Participants will be randomized to each receive one tablet of Form H and one tablet of Form II,14 days apart and undergo pharmacokinetic testing pre-dose and post-dose to evaluate safety. This is an open-label, single-dose, randomized, two-period, crossover study.

Description:

Primary Objectives:

• To evaluate the bioequivalence (BE) of brincidofovir (BCV) hydrate (Form H) tablet and the Form II tablet when administered under fasting conditions in healthy adult participants.

• To characterize plasma BCV pharmacokinetics (PK) following single doses of BCV when administered in healthy adult participants.

Safety Objective:

• To evaluate the safety of BCV following administration of single dose of 100 mg BCV Form H and BCV Form II tablet in healthy adult participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: September 27, 2023
• Est. primary completion date: August 14, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Able and willing to provide informed consent voluntarily signed by participant.

• Male or female between 18 to 70 years of age, inclusive at screening.

• Body mass index (BMI) from 18 to 32 kg/m² with a minimum body weight of = 50 kg, inclusive at screening.

• Women must be of nonchildbearing potential, i.e., postmenopausal woman (defined as spontaneous amenorrhea for 1-year prior to Period 1 Day 1) with a confirmed follicle stimulating hormone (FSH) level in laboratory's "postmenopausal" reference range; or a premenopausal woman documented as surgically sterile following either a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, tubal ligation.

• Males must be surgically sterilized (confirmed by documented azoospermia at least 90 days after procedure).

• Overtly healthy as determined by medical evaluation and judgment of the investigator including medical history, physical examination (PE), laboratory tests, vital signs (VS), and eletrocardiogram (ECG) at screening and Day -1. [Note: hematology, serum chemistry, and urinalysis parameters must fall within the laboratory's normal reference ranges or have been determined by the investigator to have no clinical significance in the context of this study.] Except:

1. Alanine transaminase (ALT), aspartate aminotransferase (AST) and gammaglutamyl transferase (GGT) x =1.5 upper limit of normal reference range (ULN)

2. Total Bilirubin x =1.5 ULN

3. Hemoglobin (Hb) =10.5 g/dL for females or =12 g/dL for males

• Able to comply with the dosing instructions and available to complete the study schedule of assessments.

Exclusion Criteria:

• History or current symptoms of any serious psychiatric illness, including addiction, which could interfere with participant treatment, assessment, or compliance with the protocol.

• History of chronic liver disease or hepatic impairment, including but not limited to alcoholic liver disease, chronic viral hepatitis, autoimmune hepatitis, steatosis, or hemochromatosis. Note: A remote (=12 months prior to screening) history of hepatitis A infection will not be cause for exclusion.

• History of Gilbert's syndrome or current evidence of the disease based on laboratory information at screening visit or Day -1.

• History of hematological disorders, including disorders such as a bleeding disorder or a risk of gastrointestinal bleeding.

• Clinically significant history of difficulty with blood donation, including vasovagal syncope (fainting), and/or poor venous access for the purposes of phlebotomy.

• Positive (reactive) serological test result at the screening evaluation consistent with possible infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus type 1 or 2 (HIV).

• Positive test for drugs of abuse and/or alcohol at either screening or check-in days.

• Clinically significant infection (e.g., COVID-19, cold, flu, or febrile illness) within 14 days prior to Period 1 Day 1.

• Donated a unit of blood or had clinically significant blood loss within 30 days prior to Period 1 Day 1 or donated plasma within 14 days prior to Period 1 Day 1.

• Received any investigational drug, agent, or device within 30 days prior to Period 1 Day 1, or current participation in another interventional study.

• Consumed any fruit juice including grapefruit juice, pomegranate juice, cranberry juice, orange juice, and Seville orange juice (also known as sour, bitter or bigarade orange) within 3 days prior to Period 1 Day 1 and throughout the study, unless prior approval is granted by both the investigator and the medical monitor.

• Received any medication or herbal product (e.g., St. John's wort) known to induce or inhibit hepatic metabolizing enzymes and/or transporters within 30 days or 5 half-lives of the compound, whichever is longer, prior to Period 1 Day 1 and throughout the study, unless approval is granted by both the investigator and the medical monitor.

• Received any vaccines (including COVID-19 vaccine) within 14 days prior to Period 1 Day 1 and throughout the study, unless approval is granted by both the investigator and the medical monitor.

• Any condition or set of circumstances that, in the judgment of the investigator, could interfere with the participant's ability to comply with the dosing schedule and completion of the study evaluations (e.g., participants who are unable to communicate or cooperate with the investigator).

Related Conditions & MeSH terms

• Smallpox

Intervention

Drug:
• Brincidofovir
100 mg tablet of Form H and 100 mg tablet of Form II

Locations

Country	Name	City	State
United States	Altasciences	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Emergent BioSolutions

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK endpoint - Peak Plasma Concentration (Cmax)	Assess maximum observed plasma concentration of Brincidofovir	Through 96 hours post-dose
Primary	PK endpoint - AUClast	Assess area under the plasma concentration-time curve from time 0 to time of the last measurable concentration (AUC 0 - last) of Brincidofovir	Through 96 hours post-dose
Primary	PK endpoint - AUCinf	Assess area under the plasma concentration-time curve from time 0 to infinity (AUC 0 - inf) of Brincidofovir	Through 96 hours post-dose
Primary	Incidence of treatment adverse events (AEs)	Incidence of treatment-emergent AEs, treatment-related AEs, severe AEs, AEs leading to withdrawal and serious adverse events	Through end of study visit (within 14 days after 2nd dose)
Primary	Descriptive statistical summary abnormal Heart Rate	Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal heart rate	Through end of study visit (within 14 days after 2nd dose)
Primary	Descriptive statistical summary abnormal Respiratory Rate	Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal respiratory rate	Through end of study visit (within 14 days after 2nd dose)
Primary	Descriptive statistical summary abnormal Systolic Blood Pressure and Diastolic Blood Pressure (mmHg)	Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal Systolic Blood Pressure	Through end of study visit (within 14 days after 2nd dose)
Primary	Descriptive statistical summary abnormal Body Temperature (Celsius)	Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal body temperature	Through end of study visit (within 14 days after 2nd dose)
Primary	Chemistry parameters: Total Protein, Albumin, Globulin (g/dL)	Descriptive statistical summary (summarized by treatment, study day, and time) of Total Protein, Albumin, Globulin	Through end of study visit (within 14 days after 2nd dose)
Primary	Chemistry parameter: Albumin/Globulin ratio	Descriptive statistical summary (summarized by treatment, study day, and time) of albumin/globulin ratio	Through end of study visit (within 14 days after 2nd dose)
Primary	Chemistry parameters: alkaline phosphatase, ALT, AST, GGT and Creatine phosphokinase (U/L)	Descriptive statistical summary (summarized by treatment, study day, and time) of alkaline phosphatase, ALT, AST, GGT and Creatine phosphokinase	Through end of study visit (within 14 days after 2nd dose)
Primary	Chemistry parameters: bilirubin (total and direct), BUN, serum calcium, glucose (random), serum phosphate, serum uric acid and serum magnesium (mg/dL)	Descriptive statistical summary (summarized by treatment, study day, and time) of bilirubin (total and direct), BUN, serum calcium, glucose (random), serum phosphate, serum uric acid and serum magnesium	Through end of study visit (within 14 days after 2nd dose)
Primary	Chemistry parameters: serum chloride, CO2, serum sodium and serum potassium (mmol/L)	Descriptive statistical summary (summarized by treatment, study day, and time) of serum chloride, CO2, serum sodium and serum potassium	Through end of study visit (within 14 days after 2nd dose)
Primary	Chemistry parameter: Creatinine (g/24h)	Descriptive statistical summary (summarized by treatment, study day, and time) of creatinine	Through end of study visit (within 14 days after 2nd dose)
Primary	Chemistry parameter: eGFR (ml/min)	Descriptive statistical summary (summarized by treatment, study day, and time) of eGFR	Through end of study visit (within 14 days after 2nd dose)
Primary	Chemistry parameter: LDH (units/L)	Descriptive statistical summary (summarized by treatment, study day, and time) of LDH	Through end of study visit (within 14 days after 2nd dose)
Primary	Hematology parameters: basophils, eosinophils, lymphocytes, monocytes and neutrophils (cells/uL)	Descriptive statistical summary (summarized by treatment, study day, and time) of basophils, eosinophils lymphocytes, monocytes and neutrophils	Through end of study visit (within 14 days after 2nd dose)
Primary	Hematology parameters: leukocytes and platelets (thousand/uL)	Descriptive statistical summary (summarized by treatment, study day, and time) of leukocytes and platelets	Through end of study visit (within 14 days after 2nd dose)
Primary	Hematology parameters: proportion of basophils, eosinophils, lymphocytes, monocytes and neutrophils	Descriptive statistical summary (summarized by treatment, study day, and time) of basophils/leukocytes, eosinophils//leukocytes, lymphocytes//leukocytes, monocytes//leukocytes and neutrophils//leukocytes	Through end of study visit (within 14 days after 2nd dose)
Primary	Hematology parameter: erythrocytes (million/uL)	Descriptive statistical summary (summarized by treatment, study day, and time) of erythrocytes	Through end of study visit (within 14 days after 2nd dose)
Primary	Hematology parameter: erythrocytes mean corpuscular volume (MCV) (fL)	Descriptive statistical summary (summarized by treatment, study day, and time) of erythrocytes MCV	Through end of study visit (within 14 days after 2nd dose)
Primary	Hematology parameter: hematocrit (%)	Descriptive statistical summary (summarized by treatment, study day, and time) of hematocrit	Through end of study visit (within 14 days after 2nd dose)
Primary	Hematology parameter: hemoglobin (g/dL)	Descriptive statistical summary (summarized by treatment, study day, and time) of hemoglobin	Through end of study visit (within 14 days after 2nd dose)