E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cohort A: Male patients with localized prostate cancer scheduled to undergo radical prostatectomy and patients with benign prostate hyperplasia scheduled to undergo simple prostatectomy
Cohort B: Male and female patients undergoing complete tonsillectomy
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Cohorte A* : Patients de sexe masculin atteints d’un cancer localisé de la prostate devant subir une prostatectomie totale (PT) et les patients atteints d’hyperplasie bénigne de la prostate (BPH) devant subir une prostatectomie simple
Cohorte B : Patients de sexe masculin ou féminin devant faire l’objet d’une amygdalectomie totale
*En France, seuls les patients avec BPH seront inclus dans la cohorte A
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E.1.1.1 | Medical condition in easily understood language |
Cohort A: Male patients with localized prostate cancer and patients with benign prostate hyperplasia
Cohort B: patients undergoing complete tonsillectomy |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To obtain pharmacokinetic data of gepotidacin in plasma and interstitial space fluid of prostate and tonsillar tissue after the administration of a single oral dose of 1500 mg gepotidacin |
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E.2.2 | Secondary objectives of the trial |
Pharmacokinetic/pharmacodynamic (PK/PD) calculations in relation to common pathogens and possible breakpoints.
Collection of safety data of gepotidacin
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Cohort A only: • Clinically localized prostate cancer or benign prostate hyperplasia • Man undergoing a 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: o Is not a woman of childbearing potential (WOCBP) or o 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
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E.4 | Principal 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 o 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
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E.5 End points |
E.5.1 | Primary end point(s) |
- area under the concentration time curve (AUC) from zero to last observed concentration (AUC0-t), AUC from zero to infinity (AUC0-∞), maximum drug concentration (Cmax), half-life (t1/2), time to reach maximum drug concentration (tmax) in tissue (calculated with a population pharmacokinetic model)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- defined time points after administration of the study drug - PK calculations will be done after chemical analysis of the concentration data is finished |
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E.5.2 | Secondary end point(s) |
• area under the concentration time curve (AUC) from zero to last observed concentration (AUC0-t), AUC from zero to infinity (AUC0-∞), Cmax, t1/2, tmax, apparent volume of distribution (Vd), Clearance (Cl) in plasma (calculated using non-compartmental analysis and a population pharmacokinetic model) • penetration ratio calculated as the ratio between the plasma (Ct, plasma) and tissue (Ct, tissue) free drug concentrations collected at the same time. • PK/PD parameters Cmax/MIC, AUC/MIC, T>MIC in tissue and plasma (if applicable) considering currently established/discussed susceptibility breakpoints of relevant pathogens • determination of target attainment for relevant pathogens • collection of adverse events during study participation
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- defined time points after administration of the study drug - PK and PK/PD calculations will be done after chemical analysis of the concentration data is finished |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |