- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04874948
Absorption, Elimination and Safety of 14C-labeled Radioactive BTZ-043, a New Compound in TB Treatment
A Single-Center, Open Label Study to Investigate the Mass Balance, Excretion Pathways and Metabolites After a Single Oral Dose of 500 MG, 3.7 MBq, [14C]BTZ-043 in Healthy Male Volunteers
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
A total of 4 evaluable subjects completing all procedures are required. Six (6) subjects will be enrolled in the cohort in order to have 4 evaluable subjects.
The study will consist of a screening period (Day -21 to -2), a baseline period (Day -1), a single dose treatment on Day 1 with a minimum of 96 hours (=4 days) post dose in-house observation period (Days -1 up to afternoon Day 5), and a follow-up visit 30 days (±2 days) after the [14C]BTZ-043 dose.
Subjects will be administered a single 500 mg [14C]BTZ-043 dose as drinking suspension. Subjects will be confined to the clinical site for at least 96 hours following drug administration (ie, afternoon of Day 5). During this time, blood, feces, and urine samples for measurement of [14C]BTZ-043 and metabolites will be collected.
The subjects will be released from the clinic approximately 96 hours to 168 hours after dose administration and upon satisfactory recovery of radioactivity (at least 90%) approved by the Sponsor's scientific advisor after consulation of the Sponsor.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Groningen, Netherlands
- PRA Health Sciences (PRA) - Early Development Services (EDS)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Sex : male
- Age : 18 years to 55 years, inclusive, at screening.
- Body mass index (BMI) : 18.0 to 29.0 kg/m2, inclusive, at screening.
- Weight : 55 to 90 kg, inclusive, at screening.
- Status : healthy subjects.
- Male subjects, if not surgically sterilized, must agree to use adequate contraception and not donate sperm from admission to the clinical research center until 90 days after the follow-up visit. Adequate contraception for the male subject (and his female partner, if she is of childbearing potential) is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm, a cervical cap, or a condom. Total abstinence, in accordance with the lifestyle of the subject, is also acceptable.
- All prescribed medication must have been stopped at least 30 days prior to admission to the clinical research center.
- All over-the-counter medications, vitamin preparations (especially vitamin C), other food supplements, and herbal medications (eg, St. John's wort) must have been stopped at least 14 days prior to admission to the clinical research center. An exception is made for paracetamol, which is allowed up to 48 hours prior to study drug administration.
- No vaccination within 14 days prior to study drug administration.
- Ability and willingness to abstain from alcohol from 48 hours (2 days) prior to screening and admission to the clinical research center.
- Ability and willingness to abstain from methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, and energy drinks), grapefruit (juice), corn (whole corn kernels and popcorn), cruciferous vegetables, and bitter oranges from 48 hours (2 days) prior to admission to the clinical research center.
- Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, ECG, and vital signs, as judged by the Investigator.
- Willing and able to sign the ICF.
Exclusion Criteria:
- Participation in another study with a radiation burden of >0.1 mSv and ≤1 mSv in the period of 1 year prior to screening; a radiation burden of >1.1 mSv and ≤2 mSv in the period of 2 years prior to screening; a radiation burden of >2.1 mSv and ≤3 mSv in the period of 3 years prior to screening, etc.
- Exposure to radiation for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton [excluding spinal column]), or during work within 1 year prior to drug administration.
- Irregular defecation pattern (less than once per day on average).
- Employee of PRA, Nuvisan, or the Sponsor.
- History of relevant drug and/or food allergies.
- Using tobacco products within 60 days prior to drug administration.
- History of alcohol abuse or drug addiction (including soft drugs like cannabis products).
- Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines, gamma-hydroxybutyric acid, tricyclic antidepressants, and alcohol) at screening or admission to the clinical research center.
- Average intake of more than 24 grams of alcohol per day.
- Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or HIV 1 and 2 antibodies.
- Participation in a drug study within 30 days prior to drug administration in the current study. Participation in more than 4 drug studies in the 12 months prior to drug administration in the current study.
- Donation or loss of more than 450 mL of blood within 60 days prior to drug administration. Donation or loss of more than 1.5 liters of blood in the 10 months prior to drug administration in the current study.
- Significant and/or acute illness within 5 days prior to drug administration that may impact safety assessments, in the opinion of the Investigator.
- Unwillingness to consume the Food and Drug Administration (FDA)-recommended high-fat breakfast.
- Unsuitable veins for infusion or blood sampling.
- Positive nasopharyngeal PCR test for SARS-CoV-2 on Day -1.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Single oral administration of 500 mg BTZ-043 containing 3.7 MBq of [14C]BTZ-043
4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043
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Single oral administration of 14C-labeled radioactive 500mg BTZ-043
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Plasma Concentration (Cmax) of total radioactivity
Time Frame: Day 1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Total radioactivity concentrations in plasma
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Day 1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Time to attain maximum observed plasma concentration (tmax) of total radioactivity
Time Frame: Day 1 to Day 5.
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Time to maximum total radioactivity concentrations in plasma
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Day 1 to Day 5.
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Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of total radioactivity
Time Frame: Day 1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Area under the plasma concentration-time curve up to time t, where t is the last point with concentrations above the lower limit of quantification
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Day 1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Area under the plasma concentration-time curve from time 0 to infinity (AUCinf) of total radioactivity
Time Frame: Day 1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Calculated as: AUC0-inf=AUC0-t+Clast/kel,where Clast is the last measurable plasma concentration
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Day 1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Terminal elimination rate constant (Kel) of total radioactivity
Time Frame: Day 1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Fraction that is eliminated from the body during a given period of time
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Day 1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Terminal elimination half-life (t1/2) of total radioactivity
Time Frame: Day 1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Day 1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Cumulative amount excreted in urine (Ae urine) of total radioactivity
Time Frame: Urine collection Day -1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Urine collection Day -1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Cumulative amount of total radioactivity excreted in feces (Ae feces)
Time Frame: Feces collection Day -2 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Feces collection Day -2 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Cumulative amount of total radioactivity excreted in vomit, if produced (Ae vomit)
Time Frame: Collection up to 8 hours after the administration of the study drug
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If produced, vomit will be collected up to 8 hours after the administration of the study drug for total radioactivity determination.
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Collection up to 8 hours after the administration of the study drug
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Total amount of total radioactivity excreted (Ae total)
Time Frame: Day -2 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Calculated as Aetotal=Aeurine+Aefeces(+Aevomit)
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Day -2 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Fraction of the total radioactivity administered excreted in urine (%) (Fe urine) of total radioactivity
Time Frame: Urine collection Day -1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Urine collection Day -1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Fraction of the total radioactivity administered excreted in feces (%) (Fe feces)
Time Frame: Feces collection Day -2 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Feces collection Day -2 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Fraction of the total radioactivity administered excreted in vomit(%) (Fe vomit)
Time Frame: If produced, vomit will be collected up to 8 hours after the administration of the study drug for total radioactivity determination.
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If produced, vomit will be collected up to 8 hours after the administration of the study drug for total radioactivity determination.
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Fraction of the total radioactivity administered (Fe total) excreted in urine, feces, and vomit (if produced) (%)
Time Frame: Urine collection Day -1 to Day 5. Feces collection Day -2 to Day 5. If produced, vomit will be collected up to 8 hours after the administration of the study drug for total radioactivity determination.
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Urine collection Day -1 to Day 5. Feces collection Day -2 to Day 5. If produced, vomit will be collected up to 8 hours after the administration of the study drug for total radioactivity determination.
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Maximum Observed Plasma Concentration (Cmax) of BTZ-043 and main metabolites
Time Frame: Day 1 to Day 3.
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Total concentrations of BTZ-043 and main metabolites in plasma
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Day 1 to Day 3.
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Time to attain maximum observed plasma concentration (tmax) of BTZ-043 and main metabolites
Time Frame: Day 1 to Day 3.
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Time to maximum concentrations of BTZ-043 and main metabolites in plasma
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Day 1 to Day 3.
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Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of BTZ-043 and main metabolites
Time Frame: Day 1 to Day 3.
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Area under the plasma concentration-time curve up to time t, where t is the last point with concentrations above the lower limit of quantification
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Day 1 to Day 3.
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Area under the plasma concentration-time curve from time 0 to infinity (AUCinf) of BTZ-043 and main metabolites
Time Frame: Day 1 to Day 3.
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Calculated as: AUC0-inf=AUC0-t+Clast/kel,where Clast is the last measurable plasma concentration
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Day 1 to Day 3.
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Terminal elimination half-life of total radioactivity (t1/2) of BTZ-043 and main metabolites
Time Frame: Day 1 to Day 3.
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Day 1 to Day 3.
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Terminal elimination rate constant (Kel) of BTZ-043 and main metabolites
Time Frame: Day 1 to Day 3.
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Fraction that is eliminated from the body during a given period of time
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Day 1 to Day 3.
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Fraction of the dose administered excreted in urine (%) (Fe urine) of BTZ-043 and main metabolites
Time Frame: Urine collection Day -1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Urine collection Day -1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Cumulative amount excreted in urine (Ae urine) of BTZ-043 and main metabolites
Time Frame: Urine collection Day -1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Urine collection Day -1 to Day 5. Further timepoints possible up to total recovery of radioactivity.
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Apparent oral clearance (CL/F) of BTZ-043
Time Frame: Day 1 to Day 3.
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Calculated as dose/AUC0-inf.
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
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Day 1 to Day 3.
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Apparent volume of distribution (Vz/F) at terminal phase of BTZ-043
Time Frame: Day 1 to Day 3.
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The theoretical volume in which the a drug would need to be distributed to produce a desired plasma concentration.
Apparent volume of distribution after oral dose is influenced by the fraction absorbed.
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Day 1 to Day 3.
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Renal clearance (CL r) of BTZ-043
Time Frame: Day 1 to Day 3.
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Hypothetical volume of plasma from which a substance is completely removed per unit time.
Using noncompartmental analysis.
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Day 1 to Day 3.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with treatment-related adverse events oncerning safety laboratory graded using the most current version of the MedDRA:
Time Frame: At screening, on Day -1 (admission), Day 2, and Day 4; and at follow-up.
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Laboratory tests: Clinical laboratory tests including clinical chemistry, hematology, and urinalysis
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At screening, on Day -1 (admission), Day 2, and Day 4; and at follow-up.
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Number of participants with treatment-related adverse events concerning vital signs graded using the most current version of the MedDRA:
Time Frame: At screening, on Day -1 (admission), Day 2, and Day 4; and at follow-up.
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Supine systolic and diastolic blood pressure, pulse, body temperature, and respiratory rate: at screening; at admission; at predose and at 1 hour, 4 hours, and 24 hours postdose; at discharge; and at follow-up.
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At screening, on Day -1 (admission), Day 2, and Day 4; and at follow-up.
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Number of participants with treatment-related adverse events concerning physical examination graded using the most current version of the MedDRA:
Time Frame: At Screening, Day -1, and follow-up/early termination
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Complete physical examinations will be conducted, Symptom driven physical examinations may be conducted at any time, per the Investigator's discretion.
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At Screening, Day -1, and follow-up/early termination
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Number of participants with treatment-related adverse events concerning 12-lead electrocardiogram graded using the most current version of the MedDRA:
Time Frame: At screening; Day -1, and 1 hour, 4 hours, and 24 hours postdose; at discharge; and at follow-up.
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12-lead ECG
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At screening; Day -1, and 1 hour, 4 hours, and 24 hours postdose; at discharge; and at follow-up.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jan Jaap van Lier, MD, PRA Health Sciences (PRA) - Early Development Services (EDS)
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Respiratory Tract Diseases
- Disease Attributes
- Bacterial Infections and Mycoses
- Gram-Positive Bacterial Infections
- Actinomycetales Infections
- Lung Diseases
- Infections
- Communicable Diseases
- Mycobacterium Infections
- Tuberculosis
- Tuberculosis, Pulmonary
- Respiratory Tract Infections
- Bacterial Infections
Other Study ID Numbers
- LMU-IMPH-BTZ-043-03
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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