Study of Spermatogenesis Suppression With DMAU Alone or With LNG Versus Placebo Alone in Normal Men

This is a Phase IIa multicenter, double-blind, placebo-controlled study in healthy men to evaluate the spermatogenesis suppression after oral administration of Dimethandrolone Undecanoate (DMAU) alone or with Levonorgestrel (LNG) for 12 weeks versus placebo alone.

This 12 week repeated dose study will be conducted at two centers: the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of Washington. The sites propose to enroll approximately 100 men with a goal of enrolling 20 healthy male subjects in each of the 4 active groups and 20 in the placebo group for 12 weeks of treatment. The goal is to complete at least 17 efficacy evaluable subjects in each group. The DMAU for this study will be castor oil formulation administered after a 25 to 30 g fat meal. The oral dose of LNG will be 30 mcg per day. The study volunteers will be randomized to one of five treatment groups:

Group 1: Lower DMAU dose (100 mg per day) + LNG (30 mcg per day) (n=20) Group 2: Middle DMAU dose (200mg per day) + LNG (30 mcg per day) (n=20) Group 3: Middle DMAU dose (200 mg per day) + placebo LNG (n=20) Group 4: Higher DMAU dose (400 mg per day) + placebo LNG (n=20) Group 5: Placebo DMAU capsules and placebo LNG capsules (n=20)

Each treatment group will receive the identical number of capsules in blinded fashion so that each subject will receive an identical number of capsules in order to maintain the blind.

Eligibility Criteria:
Men who meet all the following criteria are eligible for enrollment in the trial:

1. 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.
2. 18 to 50 years of age (inclusive) at the time of the screening visit.
3. BMI ≤36 calculated as weight in kg/ (height in m2).
4. No history of steroid hormone use in the three months prior to the first screening visit or any current medication use which might interfere with steroid metabolism.
5. Subject agrees to use a recognized effective method of contraception with any female partner (refer to Appendix 7 for acceptable forms of contraception) during the course of the study treatment and recovery phases until recovery is confirmed and study exit occurs.
6. Subjects will refrain from donating blood or plasma during the study period and from participating in other investigational drug studies.
7. Subjects will be advised to refrain from excessive alcoholic consumption during the study period. (No more than 15 drinks per week and no alcohol consumption within 24 hours of a study visit.)
8. Subjects will be advised to refrain from excessive marijuana consumption during the study period. (No more than 3 uses per week and no consumption within 24 hours of a study visit.)
9. No known or suspected current alcohol dependence syndrome, chronic marijuana use, or any illicit drug use that may affect metabolism/transformation of steroid hormones and study treatment compliance.
10. Subjects will be advised to refrain/abstain from grapefruit juice during the study period.
11. In the opinion of the investigator, subject is able to comply with the protocol, understand and sign an informed consent and HIPAA form.
12. Subjects will be advised to refrain from major changes in their level of exercise during the study period.

Men who meet any of the following criteria are NOT eligible for enrollment in the trial:

1. Men participating in another clinical trial involving an investigational drug within the 30 days prior to the first screening visit.
2. Men not living in the catchment area of the clinic or within a reasonable distance from the study site.
3. Clinically significant abnormal physical or laboratory findings at screening.
4. Elevated PSA (levels ≥ 2.5 ng/mL) at screening, according to local laboratory normal values.
5. IPSS score ≥ 10.
6. Abnormal serum chemistry values at screening, according to local laboratory reference ranges that indicate liver or kidney dysfunction or that may be considered clinically significant. In addition, the following upper limits will be observed: fasting bilirubin less than 2 mg/dL, cholesterol less than 221 mg/dL, and fasting triglycerides less than 201 mg/dL.
7. Abnormal semen analyses or abnormal semen concentration as defined by the WHO semen manual (\< 15 million/mL).
8. Use of androgens within 3 months before first screening visit except for long acting testosterone which requires a wash out period of 4 months prior to screening.
9. Ongoing use of androgens or other compounds for body building including nutritional supplements.
10. Systolic BP ≥130 mm Hg and Diastolic blood pressure BP ≥ 80 and mm Hg; Blood pressure (BP) will be taken 3 times at 5 - minute intervals and the mean of second and third measurements will be used to determine eligibility. (Note: Diagnosis of hypertension or treatment of hypertension is exclusionary.)
11. PHQ-9 score of 15 or above.
12. History of hypertension, including hypertension controlled with treatment.
13. Known history of primary testicular disease or disorders of the hypothalamic-pituitary axis.
14. Benign or malignant liver tumors; active liver disease.
15. History of breast carcinoma.
16. Known history of androgen deficiency due to hypothalamic-pituitary or testicular disease.
17. Known history of cardiovascular, renal, hepatic or prostatic disease or significant psychiatric illness.
18. Positive serology for active Hepatitis (not immunization-related serology) or HIV at screening visit.
19. A serious systemic disease such as diabetes mellitus.
20. History of known, untreated sleep apnea.
21. Partner is known to be pregnant.
22. Men desiring fertility within 12 months of signing consent for study participation.
23. Men participating in competitive sports where drug screening for prohibited substances (including anabolic steroids) is routine. Exclusion is due to the potential of testing positive for androgens that may occur from their study participation coupled with the unknown efficacy (i.e. duration of positive testing) from 12-week daily use of DMAU.
24. Use of sex steroids or medications which might interfere with steroid metabolism (i.e. ketoconazole, finasteride, oral corticosteroids, dutasteride and statins).
25. Use of medications that will interfere or interact with DMAU or LNG.
26. Known hypersensitivity to any of the active substances of DMAU, of the excipients of the study treatment, or LNG.