Session: SAT 554-583-Male Reproductive Endocrinology & Case Reports
Poster Board SAT-561
Objective: To assess the safety and pharmacokinetics (PK) of single, escalating doses of oral DMAU (powder in capsule formulation) administered with and without food in healthy men.
Design, Setting, Participants and Intervention: We conducted a randomized, placebo-controlled, double-blind study in healthy men, ages 31.7±2.3 y. For each dose, 12 male volunteers received either DMAU (n=10), or placebo (n=2) at one of two participating academic medical centers. Single oral doses of DMAU were given while fasting (25 mg, 50 mg, 100 mg, 200 mg, 400 mg, and 800 mg) and (200, 400, 800 mg) with a high fat meal (50% calories from fat). Serial serum samples were collected for 24-hours following dosing. Serum DMAU and DMA were measured by LC-MS/MS (LLOQ for DMA =0.5 and DMAU=1 ng/ml).
Results: DMAU was well tolerated, without serious adverse events at any dose. There were no clinically significant effects of DMAU on vital signs, blood counts, clinical chemistries, or electrocardiograms. When administered fasting, DMAU was detected in serum when men were given DMAU >100 mg, whereas serum DMA became detectable in all subjects only at the 800 mg DMAU dose. In contrast, when taken with a high-fat meal, serum DMA was detectable in all subjects receiving >200 mg DMAU and showed a dose proportional increase. The table shows DMA PK after 800 mg dose (N=10).
Dose Cavg (ng/ml) Cmax(ng/ml) Cmin1(ng/ml) Tmax (h) Tmin1 (h)
800mg Fasting 0.9±0.2 2.7±1.1 < 0.5 3.6±1.4 8.4±3.0
800mg Fed 11.2±1.8 52.3±11.2 1.3±0.2 6.0±0.6 24.0±0
Conclusions: This first study of DMAU administration in men demonstrates that a single, oral dose of DMAU up to 800 mg is safe and well tolerated. Co-administration of oral DMAU with food greatly enhanced absorption and improved pharmacokinetics. Reformulation of oral DMAU delivery to achieve predictable, therapeutic DMA levels in both the fasting and fed states is ongoing.
Nothing to Disclose: PS, STP, RSS, JJSN, PYL, PC, JKA, AL, LH, DLB, JW, WJB, CCW
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