Overview

The goal of this clinical trial is to evaluate three doses of the drug leflutrozole on improvement of semen quality in men with hypogonadotropic hypogonadism, a condition that affects hormone levels and fertility. It will also study the safety of leflutrozole.

The main questions it aims to answer are:

• Does leflutrozole improve semen quality?
• What medical problems do participants experience when taking leflutrozole?

Researchers will compare leflutrozole to a placebo (a look-alike substance that contains no drug).

Participants will:

• Take leflutrozole or a placebo orally once a week for 16 weeks.
• Visit the clinic every 4 weeks for checkups and tests.
• Provide semen samples to measure changes in semen quality.
• Have their blood tested to measure hormone levels and ensure safety.
• Be monitored for any side effects.

Eligibility

Inclusion Criteria:

• Signed informed consent form prior to any-related trial activity.
• Adult men aged 18-49 years (both inclusive).
• Low serum total testosterone concentration on two occasions.
• Serum Sex Hormone Binding Globulin within or above normal range at screening.
• Serum estradiol (E2) level within or above normal range at screening.
• Serum Luteinizing Hormone level within or below normal range at screening.
• Low total motile sperm count in two samples.
• Semen volume ≥1.0 mL in two samples.
• Ability to understand and comply with the requirements of the protocol.

Exclusion Criteria:

• Anatomical abnormalities of the testes or malignant or benign tumors of the testes.
• Pituitary or hypothalamic disease.
• Prostate disease.
• Treatment with one or more of the following prescription drugs or over-the-counter medications or supplements for 6 months prior to the screening visit:
  1. Compounds with androgenic or estrogenic properties (i.e., agonist or antagonist) or that affect production of sex hormones.
  2. 5-α reductase inhibitors, e.g., finasteride and dutasteride.
  3. Fertility drugs, including clomiphene, FSH, hMG and hCG preparations.
  4. Growth hormone.
  5. Opioid-receptor antagonists, e.g., naloxone and long-acting opioids.
  6. Selective α-adrenergic-receptor antagonists (alpha blockers).
  7. Topical or systemic testosterone replacement therapy (TRT).
  8. Anabolic steroids.
• Inability to reliably produce the required semen samples for trial assessments due

  to significant erectile dysfunction, anorgasmia, or other reasons.

• Participation in any clinical trial using clinical intervention within 3 months before the screening visit or 5 half-lives of investigational product administration, whichever is shorter.
• Any clinically significant 12-lead ECG abnormalities at screening.
• Known history of thromboembolic disease.
• Grade 3 lower extremity edema.
• Known cardiovascular disease.
• Known history of osteoporosis or fragility fractures.
• Known moderate or severe impairment of renal or hepatic function.
• Untreated diagnosis of sleep apnea.
• History of cancer within the last 5 years.
• Known alcohol and/or drug abuse within the last 12 months prior to randomization or evidence of such abuse indicated by the laboratory results during the screening assessments.
• Known chronic opioid use and/or misuse within the last 12 months prior to randomization.
• Any psychiatric or medical disorder or circumstance, which in the investigator's opinion might jeopardize participant's safety or compliance with the protocol.
• Hypersensitivity to any active ingredients or excipients in the medicinal products used in this trial.