Safety and Efficacy of Weekly Testosterone Cypionate Auto-Injector in Men With Hypogonadism

Inclusion criteria

• Adults assigned male at birth, aged 18 to 75 years.
• Documented diagnosis of hypogonadism (low testosterone) with at least one associated symptom, such as reduced sexual desire, erectile dysfunction, fatigue, reduced energy, loss of muscle mass, decreased body hair, or mood changes.
• Fasting morning serum total testosterone concentration below 300 ng/dL on two separate occasions, at least 72 hours apart, during screening. One additional test may be allowed if one of the initial measurements is 300 ng/dL or higher.
• Body mass index (BMI) between 18.5 and 39.9 kg/m².
• Prostate-specific antigen (PSA) level between 0 and 2.5 ng/mL for participants aged 50 years or younger, or between 0 and 4.0 ng/mL for participants older than 50 years.
• Willingness to use effective contraception throughout the study and for 30 days after the last dose of study medication.
• Low-density lipoprotein (LDL) cholesterol below 190 mg/dL.
• Hemoglobin level of 16 g/dL or lower for participants without previous testosterone replacement therapy, or 17 g/dL or lower for participants who received testosterone replacement therapy within 30 days before screening.
• Participants with diabetes must have been on a stable antidiabetic treatment regimen for at least 4 weeks before screening and have HbA1c of 9.0% or lower, or have diabetes considered adequately controlled by the investigator.
• Participants with high cholesterol or other lipid disorders must have been on stable lipid-lowering treatment for at least 4 weeks before screening or have their condition considered adequately controlled by the investigator.
• Participants with high blood pressure must have been on stable antihypertensive treatment for at least 1 month before screening or have blood pressure considered adequately controlled by the investigator. Participants with normal blood pressure who are not receiving antihypertensive treatment are also eligible.
• Participants previously receiving testosterone replacement therapy must complete the required washout period before qualifying testosterone measurements: generally 2 weeks for oral, buccal, or transdermal treatment as specified in the protocol; 5 weeks for intramuscular testosterone; or the required interval following testosterone implants.
• Adequate venous access for collection of multiple blood samples.
• Willing and able to provide written informed consent and comply with all study procedures, treatment requirements, and scheduled visits.

Exclusion criteria

• Known allergy, hypersensitivity, or unusual reaction to testosterone products or cottonseed oil.
• Current opioid use, subject to the protocol's specific medication restrictions.
• Two serum total testosterone measurements below 100 ng/dL during screening.
• Hematocrit of 52% or higher at the initial screening visit.
• Current or previous prostate cancer.
• Any cancer diagnosed or treated within the previous 5 years, except non-melanoma skin cancer.
• A prostate nodule or abnormal hardening detected during digital rectal examination.
• Significant urinary obstruction due to prostate disease or severe lower urinary tract symptoms, including an International Prostate Symptom Score (I-PSS) greater than 19.
• Severe congestive heart failure classified as New York Heart Association Class III or IV.
• Heart attack, stroke, transient ischemic attack, unstable angina requiring hospitalization, coronary angioplasty, coronary bypass surgery, uncontrolled cardiac arrhythmia, carotid artery procedure, or major peripheral vascular procedure within 6 months before screening.
• Clinically significant electrocardiogram (ECG) abnormality, history of long QT syndrome, or unexplained sudden death in a first-degree relative.
• History of or current treatment for blood clots or conditions associated with increased blood clotting, including deep vein thrombosis, pulmonary embolism, or known thrombophilia. Low-dose aspirin (81 mg) is permitted.
• Untreated sleep apnea.
• History of polycythemia vera or secondary polycythemia (an abnormally high red blood cell count).
• Clinically significant cardiovascular, kidney, liver, blood, psychiatric, neurological, endocrine, gastrointestinal, or respiratory disorder that could interfere with study participation or place the participant at increased risk, as determined by the investigator.
• Endocrine disorders requiring treatment other than hypogonadism, unless replacement medication has been stable for at least 3 months before study entry.
• Severe kidney impairment, defined as estimated glomerular filtration rate (eGFR) below 30 mL/min.
• Liver enzyme levels (ALT or AST) greater than three times the upper limit of normal.
• Positive screening test for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibody.
• History of drug or alcohol abuse within the previous 2 years that could interfere with study participation or evaluation, as determined by the investigator.
• Positive drug screening test without an appropriate documented prescription and medical indication, except where the protocol permits tetrahydrocannabinol (THC) use under applicable state law.
• Clinically significant tobacco or cigarette use within the previous 2 years, as determined by the investigator. Light smokers (5 or fewer cigarettes daily) may participate.
• Active suicidal thoughts involving a method, intent, or plan within the previous 6 months.
• Suicide attempt within the previous 12 months.
• New or worsening depression, anxiety, or suicidal thoughts within the previous 6 months, as specified in the protocol.
• Skin conditions at the intended injection site that could interfere with assessment of injection site reactions, including significant scarring, tattoos, eczema, psoriasis, urticaria, or other skin disorders.
• Tattoo removal near the intended injection site within 6 months before screening.
• Recent or current use of medications affecting testosterone concentrations or androgen activity, including finasteride, dutasteride, spironolactone, flutamide, bicalutamide, ketoconazole, anabolic steroids, or similar medications, without the required washout period.
• Use of over-the-counter products, herbal preparations, or dietary supplements known to affect testosterone levels within 7 days before study entry.
• Use of clomiphene, enclomiphene, or androgenic steroid derivatives within 6 months before screening.
• Use of anti-estrogen treatment within 90 days before screening.
• Use of estrogen, gonadotropin-releasing hormone agonists, growth hormone, or anti-androgen treatment within 12 months before screening.
• Use of dehydroepiandrosterone (DHEA), other androgens, anabolic steroids, sex hormones, or supplements affecting testosterone pharmacokinetics without completing the protocol-required washout period. DHEA requires at least 4 weeks of washout.
• Use of systemic adrenocorticotropic hormone or prohibited oral or injectable depot corticosteroids. Inhaled corticosteroids for respiratory conditions are permitted.
• Recent use of high-potency opioid medications or systemic glucocorticoids above 7.5 mg/day prednisone equivalent, subject to protocol-specified exceptions.
• Use of long-acting opioid pain medications within 1 month before treatment initiation.
• Concurrent use of medications that could significantly affect testosterone absorption, distribution, metabolism, elimination, or treatment safety.
• Participation in another investigational drug study without completing the required washout period, or use of another investigational drug during this study.
• A sexual partner planning pregnancy during the study.
• Development of gynecomastia (enlargement of male breast tissue) within the previous 6 months.
• Planned major surgical or dental procedure expected to cause blood loss of 500 mL or more during the study.
• Blood or plasma donation within 56 days before screening, or donation of more than 500 mL within the previous 3 months.
• History of poor adherence to medical treatment or concern about reliability in following study requirements, as determined by the investigator.
• Inability to understand the informed consent information in English or another language for which a certified translation is available.
• Any other condition or circumstance that, in the investigator's judgment, makes participation unsuitable or unsafe.