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Study Evaluating the Bioequivalence of Brincidofovir Form H and Form II Tablets in Healthy Adults (BCV-001)

Primary Purpose

Smallpox

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Brincidofovir
Sponsored by
Emergent BioSolutions
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Smallpox focused on measuring Smallpox, Pharmacokinetics (PK), Bioequivalence (BE), Orthopox, CMX001-129

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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: 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. 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).

Sites / Locations

  • AltasciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Treatment AB - Form H (test tablet) first

Treatment BA - Form II (reference tablet) first

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

PK endpoint - Peak Plasma Concentration (Cmax)
Assess maximum observed plasma concentration of Brincidofovir
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
PK endpoint - AUCinf
Assess area under the plasma concentration-time curve from time 0 to infinity (AUC 0 - inf) of Brincidofovir
Incidence of treatment adverse events (AEs)
Incidence of treatment-emergent AEs, treatment-related AEs, severe AEs, AEs leading to withdrawal and serious adverse events
Descriptive statistical summary abnormal Heart Rate
Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal heart rate
Descriptive statistical summary abnormal Respiratory Rate
Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal respiratory rate
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
Descriptive statistical summary abnormal Body Temperature (Celsius)
Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal body temperature
Chemistry parameters: Total Protein, Albumin, Globulin (g/dL)
Descriptive statistical summary (summarized by treatment, study day, and time) of Total Protein, Albumin, Globulin
Chemistry parameter: Albumin/Globulin ratio
Descriptive statistical summary (summarized by treatment, study day, and time) of albumin/globulin ratio
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
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
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
Chemistry parameter: Creatinine (g/24h)
Descriptive statistical summary (summarized by treatment, study day, and time) of creatinine
Chemistry parameter: eGFR (ml/min)
Descriptive statistical summary (summarized by treatment, study day, and time) of eGFR
Chemistry parameter: LDH (units/L)
Descriptive statistical summary (summarized by treatment, study day, and time) of LDH
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
Hematology parameters: leukocytes and platelets (thousand/uL)
Descriptive statistical summary (summarized by treatment, study day, and time) of leukocytes and platelets
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
Hematology parameter: erythrocytes (million/uL)
Descriptive statistical summary (summarized by treatment, study day, and time) of erythrocytes
Hematology parameter: erythrocytes mean corpuscular volume (MCV) (fL)
Descriptive statistical summary (summarized by treatment, study day, and time) of erythrocytes MCV
Hematology parameter: hematocrit (%)
Descriptive statistical summary (summarized by treatment, study day, and time) of hematocrit
Hematology parameter: hemoglobin (g/dL)
Descriptive statistical summary (summarized by treatment, study day, and time) of hemoglobin

Secondary Outcome Measures

Full Information

First Posted
June 5, 2023
Last Updated
July 5, 2023
Sponsor
Emergent BioSolutions
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1. Study Identification

Unique Protocol Identification Number
NCT05935917
Brief Title
Study Evaluating the Bioequivalence of Brincidofovir Form H and Form II Tablets in Healthy Adults
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 30, 2023 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Emergent BioSolutions

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Smallpox
Keywords
Smallpox, Pharmacokinetics (PK), Bioequivalence (BE), Orthopox, CMX001-129

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment AB - Form H (test tablet) first
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Treatment BA - Form II (reference tablet) first
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Brincidofovir
Other Intervention Name(s)
CMX001-129
Intervention Description
100 mg tablet of Form H and 100 mg tablet of Form II
Primary Outcome Measure Information:
Title
PK endpoint - Peak Plasma Concentration (Cmax)
Description
Assess maximum observed plasma concentration of Brincidofovir
Time Frame
Through 96 hours post-dose
Title
PK endpoint - AUClast
Description
Assess area under the plasma concentration-time curve from time 0 to time of the last measurable concentration (AUC 0 - last) of Brincidofovir
Time Frame
Through 96 hours post-dose
Title
PK endpoint - AUCinf
Description
Assess area under the plasma concentration-time curve from time 0 to infinity (AUC 0 - inf) of Brincidofovir
Time Frame
Through 96 hours post-dose
Title
Incidence of treatment adverse events (AEs)
Description
Incidence of treatment-emergent AEs, treatment-related AEs, severe AEs, AEs leading to withdrawal and serious adverse events
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Descriptive statistical summary abnormal Heart Rate
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal heart rate
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Descriptive statistical summary abnormal Respiratory Rate
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal respiratory rate
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Descriptive statistical summary abnormal Systolic Blood Pressure and Diastolic Blood Pressure (mmHg)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal Systolic Blood Pressure
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Descriptive statistical summary abnormal Body Temperature (Celsius)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of abnormal body temperature
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Chemistry parameters: Total Protein, Albumin, Globulin (g/dL)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of Total Protein, Albumin, Globulin
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Chemistry parameter: Albumin/Globulin ratio
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of albumin/globulin ratio
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Chemistry parameters: alkaline phosphatase, ALT, AST, GGT and Creatine phosphokinase (U/L)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of alkaline phosphatase, ALT, AST, GGT and Creatine phosphokinase
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Chemistry parameters: bilirubin (total and direct), BUN, serum calcium, glucose (random), serum phosphate, serum uric acid and serum magnesium (mg/dL)
Description
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
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Chemistry parameters: serum chloride, CO2, serum sodium and serum potassium (mmol/L)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of serum chloride, CO2, serum sodium and serum potassium
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Chemistry parameter: Creatinine (g/24h)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of creatinine
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Chemistry parameter: eGFR (ml/min)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of eGFR
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Chemistry parameter: LDH (units/L)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of LDH
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Hematology parameters: basophils, eosinophils, lymphocytes, monocytes and neutrophils (cells/uL)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of basophils, eosinophils lymphocytes, monocytes and neutrophils
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Hematology parameters: leukocytes and platelets (thousand/uL)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of leukocytes and platelets
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Hematology parameters: proportion of basophils, eosinophils, lymphocytes, monocytes and neutrophils
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of basophils/leukocytes, eosinophils//leukocytes, lymphocytes//leukocytes, monocytes//leukocytes and neutrophils//leukocytes
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Hematology parameter: erythrocytes (million/uL)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of erythrocytes
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Hematology parameter: erythrocytes mean corpuscular volume (MCV) (fL)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of erythrocytes MCV
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Hematology parameter: hematocrit (%)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of hematocrit
Time Frame
Through end of study visit (within 14 days after 2nd dose)
Title
Hematology parameter: hemoglobin (g/dL)
Description
Descriptive statistical summary (summarized by treatment, study day, and time) of hemoglobin
Time Frame
Through end of study visit (within 14 days after 2nd dose)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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: 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. 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vanja Komlenovic, MSc.
Phone
431-688-5916
Email
vkomlenovic@ebsi.com
First Name & Middle Initial & Last Name or Official Title & Degree
Dave Cassie, MSc.
Phone
204-997-0108
Email
dcassie@ebsi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dave Cassie, MSc
Organizational Affiliation
Director, Clinical Research
Official's Role
Study Director
Facility Information:
Facility Name
Altasciences
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66212
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin K Kankam, M.D.
Phone
913-696-1601
Email
mkankam@altasciences.com
First Name & Middle Initial & Last Name & Degree
Katie E Kurtz, MSN, FNP-C
Phone
913-696-1601
Email
kkurtz@altasciences.com
First Name & Middle Initial & Last Name & Degree
Martin K Kankam, M.D
First Name & Middle Initial & Last Name & Degree
Kanwal N Chaudry, M.D.
First Name & Middle Initial & Last Name & Degree
Debra J Kelsh, M.D.
First Name & Middle Initial & Last Name & Degree
Jamie S Adams, MSN, FNP-C
First Name & Middle Initial & Last Name & Degree
Katie E Kurtz, MSN, FNP-C
First Name & Middle Initial & Last Name & Degree
Catherine E Angell, MSN, FNP-C
First Name & Middle Initial & Last Name & Degree
Erin L Jorgensen, MSN, FNP-C

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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