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

NCT05935917 | Completed Phase 1 FDA Drug

• 1 other identifier: EBS-BCV-001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Smallpox

Keywords

Smallpox; Pharmacokinetics (PK); Bioequivalence (BE); Orthopox; CMX001-129

Outcome Measures

Primary Outcomes (23)

• PK endpoint - Peak Plasma Concentration (Cmax)

  Assess maximum observed plasma concentration of Brincidofovir

  Through 96 hours post-dose

• 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

• 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

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (2)

Treatment AB - Form H (test tablet) first

ACTIVE COMPARATOR

Treatment AB: Participants assigned to Treatment AB in Period 1, will be given a single 100 mg tablet of Form H (test tablet). In Period 2, participants will be given a single 100 mg tablet of Form II (reference tablet) after a 14 day washout period.

Drug: Brincidofovir

Treatment BA - Form II (reference tablet) first

ACTIVE COMPARATOR

Treatment BA: Participants assigned to Treatment BA in Period 1, will be given a single 100 mg tablet of Form II (reference tablet). In Period 2, participants will be given a single 100 mg tablet of Form H (test tablet) after a 14 day washout period.

Drug: Brincidofovir

Interventions

Brincidofovir DRUG

100 mg tablet of Form H and 100 mg tablet of Form II

Also known as: CMX001-129

Treatment AB - Form H (test tablet) first; Treatment BA - Form II (reference tablet) first

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Alanine transaminase (ALT), aspartate aminotransferase (AST) and gammaglutamyl transferase (GGT) x ≤1.5 upper limit of normal reference range (ULN)
• Total Bilirubin x ≤1.5 ULN
• 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.

You may not qualify if:

• 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 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).

Sponsors & Collaborators

• Emergent BioSolutions: lead

Study Sites (1)

Altasciences

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

Smallpox

Interventions

brincidofovir

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Dave Cassie, MSc

  Director, Clinical Research

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, single-dose, randomized, two-period, crossover study to evaluate BE of BCV plasma PK parameters after administration of single 100 mg doses of BCV using the Form H (test tablet) and Form II (reference tablet) under fasting conditions in normal healthy adults. The study will also evaluate the safety of BCV following administration of two 100 mg single doses of BCV. Eligible participants will be randomized in a 1:1 ratio to one of two treatment sequences, Treatment AB or Treatment BA.

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: July 7, 2023
• Study Start: May 30, 2023
• Primary Completion: August 14, 2023
• Study Completion: September 27, 2023
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)