Trypanosomiases, AfricanPhase 1NCT04270981
ADME Study of Acoziborole in Healthy Subjects
A Phase 1 study testing [14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 nCi) 14C in people with Trypanosomiases, African, run by Drugs for Neglected Diseases at 1 site in United Kingdom.
Trial summary
This is a single centre, open-label, single group, non-randomised, single oral dose study in healthy male subjects designed to assess the mass balance recovery, PK, metabolite profile and metabolite identification, and exploratory pharmacodynamics of acoziborole. It is planned to enrol 6 subjects. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Trypanosomiases, African
- What is being tested?
- [14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 nCi) 14C
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Feb 2020to 8 Jul 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Healthy Caucasian males.
- Age 18 to 55 years of age at the time of signing informed consent.
- Body mass index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening.
- Must be willing and able to communicate and participate in the whole study.
- Must have regular bowel movements (i.e., average stool production of ≥1 and ≤3 stools per day).
- Normal blood pressure (BP): Systolic BP between 90 and 140 (160 if >45 years old) mmHg (inclusive), diastolic BP 45 to 90 mmHg (inclusive), measured after 10 min rest in supine position at screening and pre-dose.
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- A resting heart rate (HR) between 45 and 100 bpm (inclusive), measured after 10 min rest in supine position at screening and pre-dose.
- ECG recording without clinically significant abnormality, including QTcF measure of ≤450 msec at screening and pre-dose.
- Must provide written informed consent.
- Must agree to adhere to the contraception requirements
- Subjects must be able to swallow multiple capsules.
Who cannot join
- Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1.
- Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
- History of any drug or alcohol abuse in the past 2 years
- Regular alcohol consumption >21 units per week and (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type) as confirmed by a positive alcohol breath test at screening or any on admission to the clinical unit.
- Current smokers and those who have smoked within the last 6 months. As confirmed by a breath carbon monoxide reading of greater than 10 ppm at screening or admission
- Subjects with pregnant or lactating partners.
Show all 25Show fewer
- Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 year. No occupationally exposed worker shall participate in the study.
- Subjects who have been enrolled in an ADME study in the last 12 months.
- Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening.
- Clinically significant abnormal clinical chemistry, haematology, urinalysis (especially alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) or clinically significant abnormal physical examination findings as judged by the investigator .
- Abnormal thyroid function test results
- Abnormal renal function (estimate glomerular filtration rate [eGFR] <80 mL/min).
- Confirmed positive drugs of abuse test result .
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
- History of any clinically significant acute or chronic cardiovascular, renal, hepatic, neurological (especially seizures), immunological, psychiatric, myopathies, bleeding tendency, respiratory and particularly GI disease, especially peptic ulceration and chronic gastritis, GI bleeding, ulcerative colitis, Crohn's Disease or Irritable Bowel Syndrome, as judged by the investigator.
- Any relevant GI complaints within 7 days of dosing.
- Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients.
- Presence or history of clinically significant allergy requiring treatment (including asthma, urticaria, clinically significant allergic rash or other severe allergic diathesis), as judged by the investigator. Hay fever is allowed unless it is active.
- Donation or loss of greater than 400 mL of blood within the previous 3 months or more than 100 mL within 30 days before signing ICF to this trial.
- Subjects who are taking any prescribed drug in the 14 days before screening or require regular use of any prescription medication during the study
- Subjects who have taken, any over-the-counter medications, including vitamins, analgesics or antacids, herbal remedies or St. John's wort in the 7 days before IMP administration . Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as determined by the PI.
- Use of enzyme-altering drugs (e.g. barbiturates, phenothiazines, cimetidine) within 30 days or 5 half-lives, whichever is longer, of study Day 1.
- Surgery within 12 weeks prior to screening, with the exception of appendectomy or at the discretion of the Investigator for minor surgery.
- Any surgery (e.g. gastric bypass) or medical condition that may affect absorption of orally administered drugs.
- Failure to satisfy the investigator of fitness to participate for any other reason.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label, Single-dose, Single Period Study to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of 14C-Acoziborole
This is a single centre, open-label, single group, non-randomised, single oral dose study in healthy male subjects designed to assess the mass balance recovery, PK, metabolite profile and metabolite identification, and exploratory pharmacodynamics of acoziborole. It is planned to enrol 6 subjects.
All subjects will receive an oral dose of 960 mg [14C] acoziborole on a single occasion as 4 capsules containing a small amount of radioactivity (not more than [NMT] 1000 nCi [37 KBq] 14C).
Read the detailed description
The present study aims to further understand and quantify the absorption, distribution, metabolism and elimination (ADME) of acoziborole in humans through the assessment of the mass balance recovery after a single oral dose of [14C]-acoziborole. The routes and rates of elimination of [14C]-acoziborole will be determined and plasma, urine and faecal samples will be used for metabolic profiling and structural identification.
Subjects will be screened for inclusion in the study up to 28 days before dosing. Subjects will be admitted in the evening on the day before dosing (Day 1).
Subjects will be dosed on the morning of Day 1 following an overnight fast of a minimum of 9 h, and will remain resident in the clinic until up to 240 h after dosing (up to Day 11). Subjects will return to the clinical unit for 5 additional 48 h collection periods, admitting to the clinical unit the evening before the collection period. The additional collection periods will be on Days 14 to 17, 28 to 31, 58 to 61, 88 to 91 and 118 to 121. A follow up call will take place 5 to 10 days post-final discharge to ensure the ongoing wellbeing of subjects.
- Conditions
- Trypanosomiases, African
- Being tested
- [14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 nCi) 14C
- Medical subject headings
- Trypanosomiasis, African
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 nCi) 14CDrug
Also called no other name
960 mg (4 × 240 mg capsules)of acoziborole in oral and fasted condition
| Study group | Role | What they receive |
|---|---|---|
| [14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 | Experimental | single administration of 960 mg (4 × 240 mg capsules) acoziborole in oral and fasted condition Receives: Drug: [14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 nCi) 14C |
What is being measured
The primary outcome is the main question the study is designed to answer.
total radioactivity in urines and feces
Total radioactivity in urine and faeces at each time interval and cumulative radioactivity excretion (mass balance). For the sample collection periods following 240 h after the dose, excretion will be interpolated between collection periods
Measured: 121 days
Secondary outcomes (11)
Plasma and urine concentrations of acoziborole and of its main metabolite, SCYX 3109
Plasma and urine concentrations of acoziborole and of its main metabolite, SCYX 3109, to determine relevant PK parameters
Measured: 121 days
Total radioactivity in whole blood (optional), plasma, urine and faeces
Total radioactivity in whole blood (optional), plasma, urine and faeces at each time point, to determine relevant PK parameters
Measured: 121 days
Quantitative metabolite profiling and identification of metabolites in pooled samples of plasma, urine and faeces
Quantitative metabolite profiling and identification of metabolites in pooled samples of plasma, urine and faeces, using liquid chromatography (LC)/accelerator mass spectrometry (AMS) in conjunction with LC/tandem mass spectrometry (MS-MS)
Measured: 121 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with adverse events
Safety and tolerability of 14C acoziborole after single dose as measured by d number of subjects with adverse events
Measured: 126 days
safety and tolerability of 14C acoziborole after single dose as measured by adverse events severity
Safety and tolerability of 14C acoziborole after single dose as measured by adverse events severity
Measured: 126 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with vital signs findings
Safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with vital signs findings
Measured: 121 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with 12 -lead ECG findings
Safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with 12 -lead ECG findings
Measured: 121 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with clinical laboratory tests findings (hematology)
Safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with clinical laboratory tests findings (hematology)
Measured: 121 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with clinical laboratory tests findings (biochemistry)
Safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with clinical laboratory tests findings (biochemistry)
Measured: 121 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with physical examination findings
Safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with physical examination findings
Measured: 121 days
Amount of radioactivity in plasma, faeces and urine over time
Amount of radioactivity in plasma, faeces and urine over time exploratory and optional
Measured: 121 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2020
- Study start5 Feb 2020
- Primary completion8 Jul 2020
- Study completion8 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Trypanosomiases, AfricanStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- single centre, open-label, single group, non-randomised, single oral dose study in healthy male subjects
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sharan Sidhu, MBChB, Principal investigator, Quotient Clinical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04270981
- Sponsor's protocol ID
- DNDi-OXA-03-HAT
- Status last verified
- Apr 2021
- First submitted
- 10 Feb 2020
- Last updated
- 27 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Single-dose, Single Period Study to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of 14C-Acoziborole
- ClinicalTrials.gov ID
- NCT04270981
- Acronym / sponsor ID
- DNDi-OXA-03-HAT
- Conditions
- Trypanosomiases, African
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Study start
- 5 Feb 2020 (actual)
- Primary completion
- 8 Jul 2020 (actual)
- Study completion
- 8 Jul 2020 (actual)
- First posted
- 17 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single centre, open-label, single group, non-randomised, single oral dose study in healthy male subjects designed to assess the mass balance recovery, PK, metabolite profile and metabolite identification, and exploratory pharmacodynamics of acoziborole. It is planned to enrol 6 subjects.
All subjects will receive an oral dose of 960 mg [14C] acoziborole on a single occasion as 4 capsules containing a small amount of radioactivity (not more than [NMT] 1000 nCi [37 KBq] 14C).
Detailed description
The present study aims to further understand and quantify the absorption, distribution, metabolism and elimination (ADME) of acoziborole in humans through the assessment of the mass balance recovery after a single oral dose of [14C]-acoziborole. The routes and rates of elimination of [14C]-acoziborole will be determined and plasma, urine and faecal samples will be used for metabolic profiling and structural identification.
Subjects will be screened for inclusion in the study up to 28 days before dosing. Subjects will be admitted in the evening on the day before dosing (Day 1).
Subjects will be dosed on the morning of Day 1 following an overnight fast of a minimum of 9 h, and will remain resident in the clinic until up to 240 h after dosing (up to Day 11). Subjects will return to the clinical unit for 5 additional 48 h collection periods, admitting to the clinical unit the evening before the collection period. The additional collection periods will be on Days 14 to 17, 28 to 31, 58 to 61, 88 to 91 and 118 to 121. A follow up call will take place 5 to 10 days post-final discharge to ensure the ongoing wellbeing of subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single centre, open-label, single group, non-randomised, single oral dose study in healthy male subjects
| Arm | Type | Receives |
|---|---|---|
| [14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 | Experimental | Drug: [14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 nCi) 14Csingle administration of 960 mg (4 × 240 mg capsules) acoziborole in oral and fasted condition |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy Caucasian males.
- Age 18 to 55 years of age at the time of signing informed consent.
- Body mass index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening.
- Must be willing and able to communicate and participate in the whole study.
- Must have regular bowel movements (i.e., average stool production of ≥1 and ≤3 stools per day).
Key exclusion criteria (25 listed)
- Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1.
- Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
- History of any drug or alcohol abuse in the past 2 years
- Regular alcohol consumption >21 units per week and (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type) as confirmed by a positive alcohol breath test at screening or any on admission to the clinical unit.
- Current smokers and those who have smoked within the last 6 months. As confirmed by a breath carbon monoxide reading of greater than 10 ppm at screening or admission
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 nCi) 14CAlso: no other name960 mg (4 × 240 mg capsules)of acoziborole in oral and fasted condition | Drug | [14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 |
Primary outcome
total radioactivity in urines and feces
Time frame: 121 days
Total radioactivity in urine and faeces at each time interval and cumulative radioactivity excretion (mass balance). For the sample collection periods following 240 h after the dose, excretion will be interpolated between collection periods
11 secondary outcomes
Plasma and urine concentrations of acoziborole and of its main metabolite, SCYX 3109
Time frame: 121 days
Total radioactivity in whole blood (optional), plasma, urine and faeces
Time frame: 121 days
Quantitative metabolite profiling and identification of metabolites in pooled samples of plasma, urine and faeces
Time frame: 121 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with adverse events
Time frame: 126 days
safety and tolerability of 14C acoziborole after single dose as measured by adverse events severity
Time frame: 126 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with vital signs findings
Time frame: 121 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with 12 -lead ECG findings
Time frame: 121 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with clinical laboratory tests findings (hematology)
Time frame: 121 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with clinical laboratory tests findings (biochemistry)
Time frame: 121 days
safety and tolerability of 14C acoziborole after single dose as measured by number of subjects with physical examination findings
Time frame: 121 days
Amount of radioactivity in plasma, faeces and urine over time
Time frame: 121 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sharan Sidhu, MBChB principal investigator
Quotient Clinical
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [14C]-acoziborole capsule, 240 mg containing NMT 9.25 kBq (250 nCi) 14C in people with Trypanosomiases, African, run by Drugs for Neglected Diseases at 1 site in United Kingdom.
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 11 inclusion and 25 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 27 Apr 2021. 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 United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
total radioactivity in urines and feces (time frame: 121 days). 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 27 Apr 2021.