Pharmacokinetic Study of Oral Testosterone (T) Ester Formulations in Hypogonadal Men

Phase II, Repeat Dose, Pharmacokinetic Study of Oral Testosterone Ester Formulations in Hypogonadal Men

The purpose of this pharmacokinetic study is to determine whether oral testosterone (T) ester formulations can be used effectively to treat men with low testosterone.

Determination of the steady-state serum T pharmacokinetic profiles for two oral formulations of T-esters [testosterone undecanoate (TU) and TU combined with testosterone enanthate (TE)] administered bis in die (BID) to 29 hypogonadal adult male subjects. TU was evaluated in total daily doses of 400 and 600 mg equivalents of T given twice daily for 7 or 8 days; TU + TE was evaluated in total daily doses of 600 and 800 mg equivalents of T given twice daily for 7 days. All subjects were enrolled into a single group and proceeded through the four Treatment Periods 1-4 in a sequential manner. In Treatment Period 3 the effect of food on the study-state pharmacokinetics profile of the TU formulation was evaluated.

All subjects were enrolled into a single group and proceeded through the four Treatment Periods 1-4 in a sequential manner.

Treatment Period 1: Three capsules each containing 100 mg testosterone (T) as testosterone undecanoate (TU), twice daily (BID) for 7 days. Treatment Period 2: Two capsules each containing 200 mg T as TU and testosterone enanthate (TE), BID for 7 days. Treatment Period 3: Two capsules each containing 100 mg T as TU, BID for 8 days. Treatment Period 4: Two capsules each containing 150 mg T as TU and TE, BID for 7 days.

Three capsules each containing 100 mg testosterone (T) as TU, BID. 300 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.

Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (400 mg T equivalents/dose)

Two capsules each containing 100 mg T as TU and 100 mg T as TE, BID. 400 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days. A 7-14 day washout period occurred between successive Treatment Periods.

Two capsules each containing 100 mg T as TU, BID for 8 days. 200 mg T equivalents BID 30 minutes after initiation of meals (breakfast and dinner), except for Day 8 when the morning dose was administered fasting. A 7-14 day washout period occurred between successive Treatment Periods.

Oral testosterone undecanoate (TU) combined with testosterone enanthate (TE) (300 mg T equivalents/dose)

Two capsules each containing 150 mg T as TU and 150 mg T as TE, BID. 300 mg T equivalents BID 30 minutes after initiation of breakfast and dinner meals for 7 days.

Sampling to determine serum T Cavg post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T Cavg post AM dose with food (Day 7) and fasting (Day 8) in Treatment Period 3.

30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses

Sampling to determine serum T AUC post AM and PM doses and for 24 hours in Treatment Periods 1, 2, and 4. Sampling to determine serum T AUC with food (Day 7) and fasting (Day 8) in Treatment Period 3.

30 minutes pre-dose and 0, 1, 2, 4, 8, 12 hours and 0,1, 2, 4, 8, and 12 hours post respective AM/PM doses

Inclusion Criteria: Male, ages 18-68 Serum total T less than or equal to 275 ng/dL Exclusion Criteria: Significant intercurrent disease of any type, in particular, liver, kidney or heart disease, uncontrolled diabetes mellitus or psychiatric illness. Abnormal prostate digital rectal examination, elevated prostate-specific antigen (PSA), American Urological Association (AUA) symptom score of >15, and/or history of prostate cancer. Hematocrit of <35 or >50% Body mass index (BMI) >36 Serum transaminases > 2 times upper limit of normal or serum bilirubin > 2.0 mg/dL

Yin AY, Htun M, Swerdloff RS, Diaz-Arjonilla M, Dudley RE, Faulkner S, Bross R, Leung A, Baravarian S, Hull L, Longstreth JA, Kulback S, Flippo G, Wang C. Reexamination of pharmacokinetics of oral testosterone undecanoate in hypogonadal men with a new self-emulsifying formulation. J Androl. 2012 Mar-Apr;33(2):190-201. doi: 10.2164/jandrol.111.013169. Epub 2011 Apr 7.