GonorrheaPhase 1AB-DirectNCT04484740
Penetration of the Innovative Antibiotic Gepotidacin Into Prostate and Tonsillar Tissue
A Phase 1 study testing Gepotidacin in people with Gonorrhea and Infection, Bacterial, run by Institut National de la Santé Et de la Recherche Médicale, France at 4 sites in 2 countries.
Trial summary
Gepotidacin is a new antibiotic that may potentially be used to treat prostatic infections and pharyngeal gonorrhoea. To date, no data exists on gepotidacin pharmacokinetics in those tissues. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gonorrhea, Infection, Bacterial
- What is being tested?
- Gepotidacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 29 Jan 2021to 27 May 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cohort A only:
- Clinically localized prostate cancer or benign prostate hyperplasia
- Male patient scheduled for prostatectomy
- Cohort B only:
- Male or female patient scheduled for complete tonsillectomy
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
Show all 15Show fewer
- Is not a woman of childbearing potential (WOCBP) or
- Is a WOCBP with a highly sensitive negative pregnancy test
- Both Cohorts:
- Age: above 18 years
- Body weight ≥40 kg and body mass index (BMI) within the range 18.5 - 32.0 kg/m2
- A signed and dated written informed consent form
- The subject is able to understand and willing to comply with protocol requirements and timetables, instructions and protocol-stated restrictions
- Negative serology (human immunodeficiency virus, hepatitis B-AG and C-AB) at screening
- Patient with a social security or health insurance (if applicable according to the local regulation)
Who cannot join
- Cohort A only:
- Any concerns of the investigator or the treating urologists that the participation in the study might impair histological assessment of the prostate tissue such as (but not limited to): lack of representative histology via previous biopsy AND inability to safely insert microdialysis probes in tissue with sufficient distance to the tumor (e.g. large or diffuse tumor, lack of MRI or PET image to locate tumor within the organ).
- Cohort B only:
- Pregnancy
- Women of childbearing potential who are not employing adequate contraceptive measures
- Accepted contraceptive measures are (have to be employed for at least 30 days prior to dosing until one week after the final examination):
Show all 53Show fewer
- intrauterine device
- intrauterine hormone-releasing system
- implantable progestogen-only hormone contraception associated with inhibition of ovulation
- combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal, injectable)
- progestogen-only hormone contraception associated with inhibition of ovulation (oral, injectable)
- condoms
- sexual abstinence
- surgical sterilization
- Acute tonsillitis or peritonsillar abscess
- History of peritonsillar abscess
- Tonsillectomy for cervical lymph node metastasis of cancer of unknown primary
- Both Cohorts:
- Individuals deprived of liberty and protected persons (under guardianship or curatorship).
- Medical Conditions
- Clinically significant abnormality in the past medical history or at the Screening physical examination that in the investigator's opinion may place the participant at risk or interfere with outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, renal, neurologic, gastrointestinal (GI), respiratory, hematologic, or immunologic disease.
- Any surgical or medical condition that may be aggravated by inhibition of acetylcholinesterase, such as:
- Poorly controlled asthma or chronic obstructive pulmonary disease at baseline and, in the opinion of the investigator, not stable on current therapy
- Acute severe pain, uncontrolled with conventional medical management
- Active peptic ulcer disease
- Parkinson disease
- Myasthenia gravis
- A history of seizure disorder requiring medications for control (this does not include a history of childhood febrile seizures)
- Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention, or any other condition that may place the participant at risk, in the opinion of the investigator.
- Within 2 months before Screening, either a confirmed history of Clostridium difficile diarrhoea infection or a past positive C. difficile toxin test.
- Uncompensated heart failure
- Severe left ventricular hypertrophy
- History of significant vasovagal and/or syncopal episodes or episodes of symptomatic bradycardia
- Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of drug and/or alcohol abuse within 6 months before screening, as determined by the investigator
- History of sensitivity to any of the study drug, components thereof, or a history of drug or other allergy that, in the opinion of the investigator contraindicates their participation.
- Subject is taking QT-prolonging drugs or drugs known to increase the risk of torsades de points (TdP) per the www.crediblemeds.org "Known Risk of TdP" category at the time of screening that cannot be discontinued. If discontinued they should be discontinued at screening and can be resumed after the last PK sample.
- Subject is taking strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitors CYP3A4 that cannot be discontinued. If discontinued, they should be discontinued at a minimum of 12 hours or 5 half-lifes from the scheduled gepotidacin dose and can be resumed after the last PK sample.
- Subject is taking strong P glycoprotein (P-gp) inhibitors that cannot be discontinued. If discontinued, they should be discontinued at a minimum of 12 hours or 5 half-lifes from the scheduled gepotidacin dose and can be resumed after the last PK sample.
- Prior/Concurrent Clinical Study Experience
- Previous exposure to gepotidacin. Participant has participated in a clinical trial and has received an investigational product prior to gepotidacin administration within 30 days, 5 half-lives, or twice the duration of the biological effect of investigational product (whichever is longer) Non-interventional studies are excepted.
- Diagnostic assessments
- Alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN).
- Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- History of any kidney disease or current or chronic history of impaired renal function as indicated by an estimated creatinine clearance <60 mL/min.
- History of regular alcohol consumption within 6 months of screening defined as an average weekly intake of >21 units (or an average daily intake of >3 units) for males or an average weekly intake of >14 units (or an average daily intake >2 units) for females. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 30 mL of spirits, or 100 mL of wine.
- History of regular use of more than 10 cigarettes or equivalent per day.
- Clinically significant abnormal findings in serum chemistry, hematology, or urinalysis results obtained at screening at investigators discretion
- Baseline corrected QT interval using the Fridericia formula (QTcF) of >450 msec.
- Other Exclusions
- Participant has donated blood in excess of 500 mL within 12 weeks prior to dosing or participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
- Participant is unable to comply with all study procedures, in the opinion of the investigator.
- Participant should not participate in the study, in the opinion of the investigator or sponsor.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
France3 sites
CHU POITIERS Département ORL
Poitiers, 86021
CHU POITIERS Département Urologie
Poitiers, 86021
CHRU TOURS Département Urologie
Tours, 37000
About this study
Official title: Penetration of the Innovative Antibiotic Gepotidacin Into Prostate and Tonsillar Tissue.
Gepotidacin is a new antibiotic that may potentially be used to treat prostatic infections and pharyngeal gonorrhoea. To date, no data exists on gepotidacin pharmacokinetics in those tissues. The present study is being carried out to determine concentrations of gepotidacin in plasma, prostate and tonsillar tissue of patients undergoing radical prostatectomy (RPE) for localized prostate, simple prostatectomy (PE) for benign prostate hyperplasia (BPH) or tonsillectomy (TE). This will contribute to a more complete understanding of the drug's penetration to its site of action.
Read the detailed description
A single dose of 1500 mg gepotidacin will be administered to patients who will undergo radical prostatectomy (RPE) or simple prostatectomy (PE) and patients undergoing tonsillectomy (TE). The individual time-points of gepotidacin administration will be chosen to ensure that the time-point of tissue removal corresponds with one of six different sampling time-points, as closely as possible.
After study drug administration RPE or TE will be performed according to clinical routine.
Subsequently, microdialysis (MD) probes will be inserted in the removed tissue (tonsillar or prostate tissue) ex-vivo and MD will be performed to determine unbound drug concentrations in the tissue.
Plasma PK samples will be collected just before study drug administration and up to 48h after administration of gepotidacin.
Since MD provides the concentration of the unbound fraction of gepotidacin, for comparison we will calculate the unbound fraction of the concentration values obtained through blood sampling. To this end, we will determine the protein binding using ultrafiltration for each subject at the time-point closest to the Cmax. The individual protein binding can then be used to calculate the unbound plasma fraction of gepotidacin. This will allow to transform the plasma PK data to the same scale as the microdialysis data.
Samples will be analysed using non-compartmental analysis (NCA) for plasma concentrations and population pharmacokinetic models (PopPK) for tissue concentrations pooled with plasma concentrations.
- Conditions
- Gonorrhea, Infection, Bacterial
- Being tested
- Gepotidacin
- Keywords
- tissue pharmacokinetics, gepotidacin, microdialysis
- Medical subject headings
- Gonorrhea, Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GepotidacinDrug
Single oral dose of 1500 mg gepotidacin
| Study group | Role | What they receive |
|---|---|---|
| Gepotidacin | Experimental | Not described Receives: Drug: Gepotidacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
area under the concentration time curve (AUC) from zero to last observed concentration (AUC0-t) in tissue
Pharmacokinetic parameters in tissue calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
AUC from zero to infinity (AUC0-∞) in tissue
Pharmacokinetic parameters in tissue calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
maximum drug concentration (Cmax) in tissue
Pharmacokinetic parameters in tissue calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
half-life (t1/2) in tissue
Pharmacokinetic parameters in tissue calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
time to reach maximum drug concentration (tmax) in tissue
Pharmacokinetic parameters in tissue calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
Secondary outcomes (11)
area under the concentration time curve (AUC) from zero to last observed concentration (AUC0-t) in plasma
Pharmacokinetic parameters in plasma calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
AUC from zero to infinity (AUC0-∞) in plasma
Pharmacokinetic parameters in plasma calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
Cmax in plasma
Pharmacokinetic parameters in plasma calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
t1/2 in plasma
Pharmacokinetic parameters in plasma calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
tmax in plasma
Pharmacokinetic parameters in plasma calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
apparent volume of distribution (Vd) in plasma
Pharmacokinetic parameters in plasma calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
Clearance (Cl) in plasma
Pharmacokinetic parameters in plasma calculated using a population pharmacokinetic model
Measured: Baseline to 48 hours after drug administration
T>MIC in tissue and plasma (if applicable)
PK/PD parameter
Measured: Baseline to 48 hours after drug administration
Cmax/MIC in tissue and plasma
PK/PD parameter
Measured: Baseline to 48 hours after drug administration
AUC/MIC in tissue and plasma (if applicable)
PK/PD parameter
Measured: Baseline to 48 hours after drug administration
collection of adverse events during study participation
Drug safety
Measured: at the final examination (2 to 5 days after study drug administration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2020
- Study start29 Jan 2021
- Primary completion27 May 2023
- Study completion27 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GonorrheaStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Collaborators
- Medical University of Vienna
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04484740
- Sponsor's protocol ID
- C19-28
- Other IDs
- 2019-004308-37, 2019
- Acronym
- AB-Direct
- Status last verified
- Feb 2025
- First submitted
- 10 Jul 2020
- Last updated
- 20 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Penetration of the Innovative Antibiotic Gepotidacin Into Prostate and Tonsillar Tissue.
- ClinicalTrials.gov ID
- NCT04484740
- Acronym / sponsor ID
- AB-Direct / C19-28
- Conditions
- Gonorrhea, Infection, Bacterial
- Keywords
- tissue pharmacokinetics, gepotidacin, microdialysis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Collaborators
- Medical University of Vienna
- Study start
- 29 Jan 2021 (actual)
- Primary completion
- 27 May 2023 (actual)
- Study completion
- 27 May 2023 (actual)
- First posted
- 24 Jul 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.
Gepotidacin is a new antibiotic that may potentially be used to treat prostatic infections and pharyngeal gonorrhoea. To date, no data exists on gepotidacin pharmacokinetics in those tissues. The present study is being carried out to determine concentrations of gepotidacin in plasma, prostate and tonsillar tissue of patients undergoing radical prostatectomy (RPE) for localized prostate, simple prostatectomy (PE) for benign prostate hyperplasia (BPH) or tonsillectomy (TE). This will contribute to a more complete understanding of the drug's penetration to its site of action.
Detailed description
A single dose of 1500 mg gepotidacin will be administered to patients who will undergo radical prostatectomy (RPE) or simple prostatectomy (PE) and patients undergoing tonsillectomy (TE). The individual time-points of gepotidacin administration will be chosen to ensure that the time-point of tissue removal corresponds with one of six different sampling time-points, as closely as possible.
After study drug administration RPE or TE will be performed according to clinical routine.
Subsequently, microdialysis (MD) probes will be inserted in the removed tissue (tonsillar or prostate tissue) ex-vivo and MD will be performed to determine unbound drug concentrations in the tissue.
Plasma PK samples will be collected just before study drug administration and up to 48h after administration of gepotidacin.
Since MD provides the concentration of the unbound fraction of gepotidacin, for comparison we will calculate the unbound fraction of the concentration values obtained through blood sampling. To this end, we will determine the protein binding using ultrafiltration for each subject at the time-point closest to the Cmax. The individual protein binding can then be used to calculate the unbound plasma fraction of gepotidacin. This will allow to transform the plasma PK data to the same scale as the microdialysis data.
Samples will be analysed using non-compartmental analysis (NCA) for plasma concentrations and population pharmacokinetic models (PopPK) for tissue concentrations pooled with plasma concentrations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gepotidacin | Experimental | Drug: Gepotidacin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Clinically localized prostate cancer or benign prostate hyperplasia
- Male patient scheduled for prostatectomy
- Male or female patient scheduled for complete tonsillectomy
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Age: above 18 years
Key exclusion criteria (53 listed)
- Any concerns of the investigator or the treating urologists that the participation in the study might impair histological assessment of the prostate tissue such as (but not limited to): lack of representative histology via previous biopsy AND inability to safely insert microdialysis probes in tissue with sufficient distance to the tumor (e.g. large or diffuse tumor, lack of MRI or PET image to locate tumor within the organ).
- Pregnancy
- Women of childbearing potential who are not employing adequate contraceptive measures
- Accepted contraceptive measures are (have to be employed for at least 30 days prior to dosing until one week after the final examination):
- Acute tonsillitis or peritonsillar abscess
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 |
|---|---|---|
| GepotidacinSingle oral dose of 1500 mg gepotidacin | Drug | Gepotidacin |
Primary outcome
area under the concentration time curve (AUC) from zero to last observed concentration (AUC0-t) in tissue
Time frame: Baseline to 48 hours after drug administration
Pharmacokinetic parameters in tissue calculated using a population pharmacokinetic model
AUC from zero to infinity (AUC0-∞) in tissue
Time frame: Baseline to 48 hours after drug administration
Pharmacokinetic parameters in tissue calculated using a population pharmacokinetic model
maximum drug concentration (Cmax) in tissue
Time frame: Baseline to 48 hours after drug administration
Pharmacokinetic parameters in tissue calculated using a population pharmacokinetic model
half-life (t1/2) in tissue
Time frame: Baseline to 48 hours after drug administration
Pharmacokinetic parameters in tissue calculated using a population pharmacokinetic model
time to reach maximum drug concentration (tmax) in tissue
Time frame: Baseline to 48 hours after drug administration
Pharmacokinetic parameters in tissue calculated using a population pharmacokinetic model
11 secondary outcomes
area under the concentration time curve (AUC) from zero to last observed concentration (AUC0-t) in plasma
Time frame: Baseline to 48 hours after drug administration
AUC from zero to infinity (AUC0-∞) in plasma
Time frame: Baseline to 48 hours after drug administration
Cmax in plasma
Time frame: Baseline to 48 hours after drug administration
t1/2 in plasma
Time frame: Baseline to 48 hours after drug administration
tmax in plasma
Time frame: Baseline to 48 hours after drug administration
apparent volume of distribution (Vd) in plasma
Time frame: Baseline to 48 hours after drug administration
Clearance (Cl) in plasma
Time frame: Baseline to 48 hours after drug administration
T>MIC in tissue and plasma (if applicable)
Time frame: Baseline to 48 hours after drug administration
Cmax/MIC in tissue and plasma
Time frame: Baseline to 48 hours after drug administration
AUC/MIC in tissue and plasma (if applicable)
Time frame: Baseline to 48 hours after drug administration
collection of adverse events during study participation
Time frame: at the final examination (2 to 5 days after study drug administration)
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 20 Feb 2025.
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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.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gepotidacin in people with Gonorrhea and Infection, Bacterial, run by Institut National de la Santé Et de la Recherche Médicale, France at 4 sites in 2 countries.
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 15 inclusion and 53 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 20 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France, Austria. 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?
area under the concentration time curve (AUC) from zero to last observed concentration (AUC0-t) in tissue (time frame: Baseline to 48 hours after drug administration). The study lists 5 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 20 Feb 2025.