Study to Evaluate the Effect of a Single Oral Dose of Zoliflodacin 3 g on Testicular Function in Healthy Adult Men

Official title

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of a Single Oral Dose of Zoliflodacin 3 g on Testicular Function in Healthy Adult Men

Overview

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

• Drug Zoliflodacin
  Oral suspension of Zoliflodacin 3g
• Drug Placebo
  Oral suspension of matching placebo

Primary outcome measures

• Sperm concentration [Time frame: Week 13 (and potentially week 26)]

Secondary outcome measures (7)

• Semen Volume [Time frame: At baseline and week 13]
• Sperm count [Time frame: At Baseline and week 13]
• Progressive mobility [Time frame: At Baseline and Week 13]
• Morphology [Time frame: At baseline and week 13]
• Serum Hormones (LH) [Time frame: At Baseline and Week 13]
• Serum hormones (FSH) [Time frame: At Baseline and Week 13]
• Serum Hormones (Testosterone) [Time frame: At baseline and week 13]

Eligibility criteria

Inclusion criteria

• Man with good general health status, as determined by medical history, physical examination, screening laboratory tests, vital signs (including temperature), and clinical judgment
• Age 18 to 45 years at informed consent
• Weight ≥35 kg at Screening
• Laboratory results at Screening, including FSH, LH, and total testosterone, within laboratory reference ranges
• 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%
• 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
• Provision of written informed consent
• Willingness to participate and comply with all aspects of the trial through the entire trial period

Exclusion criteria

• 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
• Prior diagnosis of male impaired fertility (including reduced fertility)
• History of antisperm antibodies
• History of radiation to the testicles
• History of clinically significant trauma to or surgery on the scrotum or testicles, including vasectomy
• Known hypersensitivity to zoliflodacin or formulation excipients
• Disorders of sperm transport including, but not limited to, retrograde ejaculation and immotile cilia syndrome
• Sexual dysfunction of a nature that would prevent sperm collection in accordance with the protocol requirements (phosphodiesterase inhibitor use is permitted)
• Uncontrolled thyroid dysfunction (e.g., untreated hypothyroidism or hyperthyroidism)
• 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
• History of major surgery or trauma within 4 weeks before Day 1 or anticipated need for major surgery during the trial
• Febrile illness within 4 weeks before Screening
• Clinically significant urinary tract infection, prostatitis, epididymitis, or STI diagnosed or treated within 4 weeks before Screening
• Genitourinary sign or symptom indicative of a current STI (urethral discharge, dysuria, or genital lesion) at Screening or Day 1
• Positive nucleic acid amplification test (NAAT) result for N gonorrhoeae at Screening
• 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
• 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
• 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
• Current tobacco use of ≥1 pack/day or equivalent
• Current alcohol use >5 units per week
• Known or suspected drug abuse
• A positive drug or alcohol screen result at Screening or Day 1 visit
• Participation in an interventional clinical study within 30 days or 5 half-lives of the study drug, whichever is longer, before Day 1 -

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Screening

Study locations

Germany · 1 center

• Parexel EPCU — Berlin

United Kingdom · 1 center

• Parexel EPCU — London

Identifiers

NCT: NCT07640477 · STI_PMR_Zoli007

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗