AzTrials
AzTrials

TuberculosisPhase 1NCT04874948

Absorption, Elimination and Safety of 14C-labeled Radioactive BTZ-043, a New Compound in TB Treatment

A Phase 1 study testing 500mg BTZ-043 containing 3.7 MBq of [14C]BTZ-043 in people with Tuberculosis and Tuberculosis, Pulmonary, run by Michael Hoelscher at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is a Phase 1, single-center, open-label study to investigate the absorption, metabolism, and excretion of BTZ-043 after a single oral administration of 500 mg BTZ-043 containing 3.7 MBq of [14C]BTZ-043 in 4 healthy adult male subjects Read more about this study

Who is it for?
Ages 18 to 55 years, men onlyHealthy volunteers can take part
What is being tested?
500mg BTZ-043 containing 3.7 MBq of [14C]BTZ-043
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteNetherlands
Study dates
8 Oct 2021to 9 Nov 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
Show all 13Show fewer
  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site
  • PRA Health Sciences (PRA) - Early Development Services (EDS)

    Groningen

Other trials in Netherlands

About this study

Official title: 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

This study is a Phase 1, single-center, open-label study to investigate the absorption, metabolism, and excretion of BTZ-043 after a single oral administration of 500 mg BTZ-043 containing 3.7 MBq of [14C]BTZ-043 in 4 healthy adult male subjects

Read the 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.

Being tested
500mg BTZ-043 containing 3.7 MBq of [14C]BTZ-043
Keywords
Anti-Bacterial Agents
Medical subject headings
Tuberculosis, Tuberculosis, Pulmonary, Lung Diseases, Mycobacterium Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 500mg BTZ-043 containing 3.7 MBq of [14C]BTZ-043Drug

    Single oral administration of 14C-labeled radioactive 500mg BTZ-043

Study groups in NCT04874948
Study groupRoleWhat they receive
Single oral administration of 500 mg BTZ-043 containing 3.7 MBq of [14C]BTZ-043Experimental4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043
Receives: Drug: 500mg BTZ-043 containing 3.7 MBq of [14C]BTZ-043

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rates and Routes of Excretion

    To determine the rates and routes of excretion of [14C]BTZ-043-related radioactivity, including mass balance of total drug-related radioactivity in urine and feces (and vomit, if applicable), following the oral administration of a single 500 mg dose of [14C]BTZ-043 in healthy male volunteers. All excreta were collected for the analysis for 14C quick or normal counts of total radioactivity (as feasible). the radioactivity measured was translated into mg eq (Radioactivity equivalent to 1 mg BTZ-043).

    Measured: Urine and faeces were collected from the administration of the study medication until cumulative excretion reached 90% of total radioactivity administered. This was achieved by all subjects after 168 hours.

  2. Pharmacokinetics of Total Radioactivity in Blood and Plasma (Cmax)

    To determine the pharmacokinetics (PK) of total radioactivity in whole blood and in plasma. Measured radioactivity was translated into ng equivalent of BTZ-043. Based on the ng eq, pharmacokinetic parameters were calculated.

    Measured: Blood samples for total radioactivity were collected from day 1 until 168 h post dosing

  3. Pharmacokinetics of Total Radioactivity in Blood and Plasma (AUC-t)

    To determine the pharmacokinetics (PK) of total radioactivity in whole blood and in plasma. Measured radioactivity was translated into ng equivalent of BTZ-043. Based on the ng eq, pharmacokinetic parameters were calculated.

    Measured: Blood samples for total radioactivity were collected from day 1 until 168 h post dosing

  4. Pharmacokinetics of Total Radioactivity in Blood (T1/2)

    To determine the pharmacokinetics (PK) of total radioactivity in whole blood and in plasma. Measured radioactivity was translated into ng equivalent of BTZ-043. Based on the ng eq, pharmacokinetic parameters were calculated.

    Measured: Blood samples for total radioactivity were collected from day 1 until 168 h post dosing

  5. Pharmacokinetics of Total Radioactivity in Plasma (T1/2)

    To determine the pharmacokinetics (PK) of total radioactivity in whole blood and in plasma. Measured radioactivity was translated into ng equivalent of BTZ-043. Based on the ng eq, pharmacokinetic parameters were calculated.

    Measured: Blood samples for total radioactivity were collected from day 1 until 168 h post dosing

  6. Plasma PK of BTZ-043 and Main Metabolites (Cmax)

    To characterize the plasma PK of BTZ-043 and main metabolites by liquid chromatography-mass spectrometry (LC-MS), if applicable. BTZ-043 is metabolized in the human body. Some of the metabolites were known prior to this study like the main metabolite M2, a hydrid Meisenheimer complex or the aminometabolite M1. Metabolite M4 and M10 were known before as well, therefore, the bioanalytical methods mentioned above could be developed and validated for these metabolites.Pharmacokinetic parameters are calculated from the individual plasma level measurements.

    Measured: Day 1 to Day 3

  7. Plasma PK of BTZ-043 and Main Metabolites (AUC-last)

    To characterize the plasma PK of BTZ-043 and main metabolites by liquid chromatography-mass spectrometry (LC-MS), if applicable. BTZ-043 is metabolized in the human body. Some of the metabolites were known prior to this study like the main metabolite M2, a hydrid Meisenheimer complex or the aminometabolite M1. Metabolite M4 and M10 were known before as well, therefore, the bioanalytical methods mentioned above could be developed and validated for these metabolites. Pharmacokinetic parameters are calculated from the individual plasma level measurements.

    Measured: Day 1 to Day 3

  8. Plasma PK of BTZ-043 and Main Metabolites (t1/2)

    To characterize the plasma PK of BTZ-043 and main metabolites by liquid chromatography-mass spectrometry (LC-MS), if applicable. BTZ-043 is metabolized in the human body. Some of the metabolites were known prior to this study like the main metabolite M2, a hydrid Meisenheimer complex or the aminometabolite M1. Metabolite M4 and M10 were known before as well, therefore, the bioanalytical methods mentioned above could be developed and validated for these metabolites. Pharmacokinetic parameters are calculated from the individual plasma level measurements.

    Measured: Day 1 to Day 3

  9. Urine Concentrations of BTZ-043 and Main Metabolites

    Urine volume was measured after every micturation and hamilton pools have been prepared for analysis of BTZ-043 and main metabolites by LC-MS. BTZ-043 could only be measured in urine within the first 24h, then no additional BTZ-043 was excreted in urine anymore. The same applies for M1. M2, M4 total and M10 total excretion could be measured in urine up to 48h post dose.

    Measured: Assessed from time of dosing up to 168 h post dose. BTZ-043 and metabolites were excreted fom 0 - 24 h (BTZ-043 and M1) and from 0 - 48 h (M2, M4 total and M10 total).

Secondary outcomes (1)
  1. Number of Adverse Events

    To assess the safety and tolerability of a single 500 mg oral dose of BTZ-043 administered to healthy volunteers.

    Measured: Day -1 to day 32

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 May 2021
  2. Study start8 Oct 2021
  3. Primary completion15 Oct 2021
  4. Study completion9 Nov 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04874948
Sponsor's protocol ID
LMU-IMPH-BTZ-043-03
Status last verified
Dec 2024
First submitted
22 Apr 2021
Last updated
31 Dec 2024
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 500mg BTZ-043 containing 3.7 MBq of [14C]BTZ-043 in people with Tuberculosis and Tuberculosis, Pulmonary, run by Michael Hoelscher at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rates and Routes of Excretion (time frame: Urine and faeces were collected from the administration of the study medication until cumulative excretion reached 90% of total radioactivity administered. This was achieved by all subjects after 168 hours.). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2024.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in