Phase 1 Study of Dimethandrolone Undecanoate in Healthy Men

The study will be conducted in two centers.

28-Day Repeat-Dose, Dose-Escalation Study: Based on the safety and tolerability of the single dose study and serum DMA levels attained, three doses of two formulations of DMAU were selected for a dose-escalating 28-day repeat dose study. Safety will be assessed in subjects receiving lower dosages before additional men receive higher doses for 28 days. Up to 100 men will be randomized to receive either active drug or an identical number of capsules of placebo. The 24-hour detailed PK of DMA will be assessed on day 1 and 28. Trough levels of DMA will be obtained throughout the 28-day period and at 48 and 72 hours after the last dose. In addition to safety and tolerability, suppression of serum T, gonadotropins, and SHBG will also be assessed as secondary pharmacodynamic (PD) endpoints. Psychosexual diaries for 7 consecutive days and PHQ-9 (questionnaire)will be obtained before and at the end of the study period.

Inclusion criteria

• Male volunteers in good health as confirmed by physical examination, medical history, and clinical laboratory tests of blood and urine at the time of screening.
• 18 to 50 years of age.
• BMI < 33 calculated as weight in kg/ (height in m2 )
• No history of hormonal therapy use in the last three months prior to the first screening visit.
• Subject will agree to use a recognized effective method of contraception with his partner (i.e. at a minimum, use double-barrier contraception) during the course of the study treatment and recovery phase.
• Subjects will refrain from donating blood or plasma during the study period.
• Subjects will be advised to refrain/abstain from alcoholic beverages and grapefruit juice during the study period.
• Subjects will not use cannabis or any recreational drugs at least 4 weeks before screening and during the study.
• In the opinion of the investigator, subject is able to comply with the protocol, understand and sign an informed consent and HIPAA form.
• Does not meet any of the exclusion criteria.

Exclusion criteria

• Men participating in another clinical trial involving an investigational drug within the last 30 days prior to the first screening visit.
• Men not living in the catchment's area of the clinic or within a reasonable distance from the study site.
• Clinically significant abnormal physical and laboratory findings at screening.
• Elevated PSA (levels ≥ 2.5 ng/mL), according to local laboratory normal values.
• Abnormal serum chemistry values, according to local laboratory reference ranges that indicate liver or kidney dysfunction or that may be considered clinically significant except for: an upper limit for fasting bilirubin is less than 2 mg/dL, upper limit for cholesterol is less than 220 mg/dL, or upper limit for fasting triglycerides is less than 200 mg/dL.
• Abnormal semen analyses or abnormal semen concentration as defined by the WHO semen manual.
• Use of androgens or other body building substances including nutritional supplements within 3 months before first screening visit.
• Systolic BP > 130 mm Hg and Diastolic blood pressure BP > 80 and mm Hg; ((BP) Blood pressure will be taken 3 times at 5-minute intervals and the mean of all measurements be considered).
• Clinically significant abnormal EKG and a QTc interval of > 450 msec.
• PHQ-9 score of 15 or above [for the 28 days study].
• History of hypertension, including hypertension controlled with treatment.
• Known history of primary testicular disease or disorders of the hypothalamic-pituitary axis.
• Benign or malignant liver tumors; active liver disease.
• History of breast carcinoma.
• Known history of androgen deficiency due to hypothalamic-pituitary or testicular disease.
• Known history of cardiac, renal, hepatic or prostatic disease.
• Positive serology for Hepatitis or HIV at screening visit.
• A serious systemic disease such as diabetes mellitus or obesity (body weight greater than BMI >33 kg/m2 as above).
• History of known, untreated sleep apnea.
• Known or suspected alcoholism or drug abuse that may affect metabolism/transformation of steroid hormones and study treatment compliance.
• Partner is known to be pregnant.
• Men desiring fertility within the first 24 weeks of study participation.
• Men participating in competitive sports where drug screening for prohibited substances (including anabolic steroids) is routine will be advised of the relative and temporary hazards that participating in this study may have for their fertility or sporting status.