This is a Phase I multicenter, double-blind, single dose, dose-ranging study, in healthy men to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics of Dimethandrolone Undecanoate (DMAU) administered as an intramuscular or subcutaneous injection.
This single dose, dose-ranging study will be conducted in two centers: the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the University of Washington. Single doses of DMAU in castor oil/benzyl benzoate injections intramuscularly (IM) (80 mg, 240 mg, 480 mg, and 800 mg) or administered subcutaneously (SC) (50 mg, 100 mg and 200 mg) were selected for this dose-escalating study. Twelve subjects will complete this study at each of the DMAU doses (10 on DMAU and 2 on placebo injections) yielding a total of 84 completed subjects (70 on DMAU and 14 on placebo) across both sites. Safety will be assessed in all subjects and recovery will be assessed in two subjects receiving lower doses, either IM or SC, before additional men receive higher doses of IM or SC of DMAU. In addition to safety and tolerability, suppression of serum T, E2, gonadotropins, and SHBG will be assessed as secondary pharmacodynamic (PD) endpoints. PK of DMAU and DMA will be assessed through blood draws done at each visit. Suppression of spermatogenesis will be assessed with semen analysis. DMAU injections will be administered at the study site by research nurses or physicians. For intramuscular injections, the staff will inject DMAU in castor oil into the gluteal region following standard procedures for intramuscular steroid injection. Abdominal subcutaneous injections will follow standard subcutaneous procedures. The subject will be observed for at least 30 minutes before release from the study site.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
106
Single doses of DMAU in castor oil/benzyl benzoate injections intramuscularly (IM) (80 mg, 240 mg, 480 mg, and 800 mg) or administered subcutaneously (SC) (50 mg, 100 mg and 200 mg).
Placebo injections that look like the DMAU injections but with no active ingredients
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California, United States
University of Washington Medical Center & Health Sciences
Seattle, Washington, United States
Incidence of treatment emergent adverse events (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in sexual function (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) using the psychosexual daily questionnaire
Time frame: 5-7 months
Changes from baseline in mood (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU) using the Patient Health Questionnaire-9
Time frame: 5-7 months
Changes from baseline in sodium (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in potassium (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in chloride (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in bicarbonate (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in fasting glucose (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in blood urea nitrogen (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
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Time frame: 5-7 months
Changes from baseline in creatinine (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in calcium (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in total bilirubin (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in alkaline phosphatase (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in alanine aminotransferase (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in aspartate transaminase (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in albumin (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in blood pressure (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in pulse (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in respiratory rate (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Changes from baseline in body mass index (safety and tolerability) with a single IM or SC injection of escalating doses of Dimethandrolone Undecanoate (DMAU)
Time frame: 5-7 months
Pharmacokinetics of DMAU and DMA using AUC (0-t, where t is the last time-point with measurable concentration)
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of serum Testosterone (T) using mean values at each visit
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of Dihydrotestosterone (DHT) using mean values at each visit
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of Estradiol (E2) using mean values at each visit
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of Follicle Stimulating Hormone (FSH) using mean values at each visit
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of Luteinizing Hormone (LH) using mean values at each visit
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of Sex Hormone Binding Globulin (SHBG) using mean values at each visit
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of serum T using number of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of serum T using percentage of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of DHT using number of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of DHT using percentage of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of E2 using number of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of E2 using percentage of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of FSH using number of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of FSH using of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of LH using number of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of LH using percentage of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of SHBG using number of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Pharmacodynamics of DMAU by assessing the suppression of SHBG using percentage of subjects with FSH and LH ≤ 1.0 IU/L
Time frame: 5-7 months
Suppression of spermatogenesis as assessed by semen analyses using number of subjects with sperm concentration <1 million (M)/mL
Time frame: 5-7 months
Suppression of spermatogenesis as assessed by semen analyses using percentage of subjects with sperm concentration <1 million (M)/mL
Time frame: 5-7 months