Overview

Penetration of the Innovative Antibiotic Gepotidacin Into Prostate and Tonsillar Tissue

Status:
Not yet recruiting
Trial end date:
2021-12-01
Target enrollment:
0
Participant gender:
All
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. 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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Institut National de la Santé Et de la Recherche Médicale, France
Collaborator:
Medizinischen Universität Wien
Criteria
Inclusion Criteria:

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:

- 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)

Exclusion Criteria:

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):

- 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.