Testicular Abnominalies
Conditions
Keywords
Testicular toxicities
Brief summary
This study is a randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of zoliflodacin on testicular function in healthy adult men. Participants will be screened within 21 days before randomization (Day 1), including collection of 2 semen samples (each collected after a ≥48 hours and ≤7 days ejaculation-free period). Approximately 220 participants who provide written informed consent and meet all inclusion and no exclusion criteria will be enrolled and randomized in a 1:1 fashion to receive a single dose of either zoliflodacin 3 g or placebo administered as an oral suspension on Day 1. Each participant will be contacted by telephone at Week 1 and at Week 7 post dosing to review adverse events (AEs), concomitant medications and procedures, and genitourinary symptoms. Each participant will return to the trial site at Week 13 for collection of 2 semen samples (each collected after a ≥48 hours and ≤7 days ejaculation-free period). A serum sample will also be collected for hormone testing (luteinizing hormone \[LH\], follicle-stimulating hormone \[FSH\], and total testosterone) at Week 13 to support biological interpretation of any decrease in sperm concentration. Participants who do not have a ≥50% decrease from baseline in sperm concentration at Week 13 will complete the trial at Week 13 (end of trial). Participants with a ≥50% decrease from baseline in sperm concentration at Week 13 will return to the trial site at Week 26 for collection of 2 semen samples (independent ejaculates, each collected after a ≥48 hours and ≤7 days ejaculation-free period) for evaluation of the reversibility of the Week 13 finding, following completion of a one additional spermatogenic cycle post completion of dosing/drug exposure (FDA 2018) (end of trial). All Adverse Events, medications, and procedures will be recorded from the signing of the informed consent form (ICF) through the end-of-trial visit (Week 13, Week 26, or Early Termination)
Interventions
DRUGZoliflodacin
Oral suspension of Zoliflodacin 3g
DRUGPlacebo
Oral suspension of matching placebo
Sponsors
Global Antibiotics Research and Development Partnership
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double blind, placebo controlled
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Man with good general health status, as determined by medical history, physical examination, screening laboratory tests, vital signs (including temperature), and clinical judgment 2. Age 18 to 45 years at informed consent 3. Weight ≥35 kg at Screening 4. Laboratory results at Screening, including FSH, LH, and total testosterone, within laboratory reference ranges 5. Semen parameters for each semen sample collected during Screening meeting the following criteria (WHO 2021): * sperm concentration ≥16 million/mL * semen volume ≥1.4 mL * total sperm per ejaculate ≥39 million * progressive motility ≥ 30% * sperm morphology : normal forms ≥4% 6. Willingness to use a highly effective form of contraception with female sexual partners of reproductive potential for 3 months after the last study drug dose 7. Provision of written informed consent 8. Willingness to participate and comply with all aspects of the trial through the entire trial period
Exclusion criteria
1. History of male reproductive health issues including, but not limited to, known hypothalamic-pituitary disorders (e.g., pituitary macroadenomas, pituitary infarction, hyperprolactinemia, panhypopituitarism), primary hypogonadism (e.g., cryptorchidism, Klinefelter's syndrome), Grade III varicocele, testicular torsion, orchitis, unilateral orchiectomy, or prostate gland pathology 2. Prior diagnosis of male impaired fertility (including reduced fertility) 3. History of antisperm antibodies 4. History of radiation to the testicles 5. History of clinically significant trauma to or surgery on the scrotum or testicles, including vasectomy 6. Known hypersensitivity to zoliflodacin or formulation excipients 7. Disorders of sperm transport including, but not limited to, retrograde ejaculation and immotile cilia syndrome 8. Sexual dysfunction of a nature that would prevent sperm collection in accordance with the protocol requirements (phosphodiesterase inhibitor use is permitted) 9. Uncontrolled thyroid dysfunction (e.g., untreated hypothyroidism or hyperthyroidism) 10. Any chronic medical or psychiatric condition that, in the opinion of the investigator, may harm the participant or make the participant unsuitable for the trial or would prevent compliance with the trial protocol procedures 11. History of major surgery or trauma within 4 weeks before Day 1 or anticipated need for major surgery during the trial 12. Febrile illness within 4 weeks before Screening 13. Clinically significant urinary tract infection, prostatitis, epididymitis, or STI diagnosed or treated within 4 weeks before Screening 14. Genitourinary sign or symptom indicative of a current STI (urethral discharge, dysuria, or genital lesion) at Screening or Day 1 15. Positive nucleic acid amplification test (NAAT) result for N gonorrhoeae at Screening 16. Positive serologic test for HIV-1 or HIV-2 antibody, hepatitis B surface antigen, or hepatitis C antibody or for any other pathogen tested according to the trial site standards for blood and semen handling 17. Use within 13 weeks before Screening of or anticipated need during the trial for a medication known to affect spermatogenesis or reproductive hormone regulation including, but not limited to, the following medications: * testosterone * gonadotropin analogues * anabolic steroids * antiandrogens (e.g., spironolactone, finasteride, dutasteride, ketoconazole) * 5-α reductase inhibitors * α-1 blockers * chemotherapeutic agents * chronic (≥90 days) use of opioids * other hormone-modulating medications 18. Use within 14 days before Day 1 of a moderate or strong cytochrome P450 isoenzyme 3A4 (CYP3A4) inducer (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort) or anticipated need for moderate or strong CYP3A4 inducers from Day 1 to Day 3 19. Current tobacco use of ≥1 pack/day or equivalent 20. Current alcohol use \>5 units per week 21. Known or suspected drug abuse 22. A positive drug or alcohol screen result at Screening or Day 1 visit 23. Participation in an interventional clinical study within 30 days or 5 half-lives of the study drug, whichever is longer, before Day 1 -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sperm concentration | Week 13 (and potentially week 26) | Percentage of participants with a ≥50% decrease from baseline in sperm concentration (million/mL) at Week 13 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Semen Volume | At baseline and week 13 | Change in semen volume (in mL) |
| Sperm count | At Baseline and week 13 | Total sperm count per ejaculate (million) |
| Progressive mobility | At Baseline and Week 13 | Sperm exhibiting active forward movement (μm/s) |
| Morphology | At baseline and week 13 | Evaluated using Tygerberg Strict Criteria (%) |
| Serum Hormones (LH) | At Baseline and Week 13 | Change in luteinizing hormone (LH), shift analysis relative to reference ranges |
| Serum hormones (FSH) | At Baseline and Week 13 | Change in Follicle Stimulating Hormone (FSH), shift analysis relative to reference ranges |
| Serum Hormones (Testosterone) | At baseline and week 13 | Change in Testosterone, shift analysis relative to reference ranges |
Countries
Germany, United Kingdom
Contacts
CONTACTJovana Albig, MD
Outcome results
None listed