A Phase 1/2a Study to Determine the Dose Response Pharmacokinetics of TSX-011 (Testosterone Undecanoate) in Hypogonadal Males

This will be a phase 1/2a, open-label, single-center study with 3 periods. The aims of the
study are to: 1) evaluate the dose-response curve following ascending single doses of
TSX-011; 2) confirm optimum dosing conditions; 3) evaluate the efficacy of single or multiple
daily adaptive dosing; and 4) evaluate the safety and tolerability of TSX-011. Up to 24
hypogonadal men will be enrolled in this study to yield 16 evaluable subjects, and it is
desired that the same 24 subjects participate in all 3 study periods.

Period 1 is an ascending single-dose study of TSX-011 at 3 doses, with the lowest dose
administered under fed and fasted conditions: 190 mg TSX-011 in the fed state, 190 mg TSX-011
in the fasted state, 380 mg TSX-011 in the fed state, and 570 mg TSX-011 in the fed state.
Before exposure to TSX-011, a 24 hour baseline measurement of testosterone and DHT will be
performed for each subject. Samples for analysis of testosterone will be obtained at the
following time points on Day -1: hour 0 (8 am ± 60 minutes) and 1.5, 3, 4.5, 6, 8, 12, 16,
and 24 hours (± 15 minutes for each time point).

The day following the sampling for endogenous testosterone (Day 1) in Period 1, each subject
will receive the first single dose of TSX-011 (190 mg) under fed conditions. Following
administration of TSX-011, blood samples will be obtained over a 24-hour period for PK
analysis. Subjects will undergo a minimum 3-day and up to 7-day washout period between each
of the doses of TSX-011 in Period 1. After the 570 mg TSX 011 dose in Period 1, a minimum
3-day and up to 7-day washout period will occur before the start of Period 2.

Period 2 is a twice-daily dosing period, where fed subjects will be dosed with 380 mg TSX-011
twice daily for 15 days (Days 1 through 15). Pharmacokinetic assessments over 24 hours will
occur on Days 1 and 15. The TSX-011 dose will be titrated up or down beginning with the Day
16 (Period 3) morning dose, based on established dosing rules.

Period 3 is a dose-adjusted adaptive design period that begins on Day 16, with the first
adjusted TSX-011 dose administered in the fed state on a once-daily or twice-daily schedule.
The 6-hour postdose (± 15 minutes) testosterone level on Day 19 will be used to perform the
second and final TSX-011 dose adjustment, based on established criteria. As specified by the
dose adjustment rules, Day 26 begins with either a once-daily, twice-daily, or thrice-daily
fed dose schedule. The thrice-daily dose schedule will be administered only to
non-responders. On Day 30, a 24 hour PK assessment will be performed, and the subject's
participation in the study is completed the morning of Day 31.

Inclusion Criteria:

- Testosterone level <350 ng/dL, 10 am [± 2 hour] sample.

- Body mass index (BMI) <35.0 kg/m2 and weight ≥50 kg

Exclusion Criteria:

- History of clinically significant renal, hepatic, neurologic, hematologic, endocrine,
oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease or any other
condition.

- Significant gastrointestinal or malabsorption conditions.

- Any man in whom testosterone therapy is contraindicated including the following:

1. Known or suspected carcinoma (or history of carcinoma) of the prostate,
clinically significant symptoms of benign prostatic hyperplasia, and/or
clinically significant symptoms of lower urinary obstruction and International
Prostate Symptom Score (IPSS) ≥19. A clinically significant digital rectal
examination of the prostate or clinically significant elevated serum PSA levels
(>4.0 ng/mL).

2. Known or suspected carcinoma (or history of carcinoma) of the breast.

3. Liver disease defined as alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) >2 × upper limit of normal (ULN) or bilirubin >2 × ULN.

4. Active deep vein thrombosis or thromboembolic disorder, or a documented history
of these conditions.

5. Untreated sleep apnea.

6. Hematocrit >50%.

7. Untreated moderate to severe depression.

- Current use of long-acting testosterone or any of the testosterone esters injectables.

- Topical, oral, or injectable testosterone replacement therapy.

- Clinically significant changes in any medications (including dosages) or medical
conditions in the 28 days before screening.

- Suspected reversible hypogonadism (e.g., leuprolide injection).

- Taking concomitant medications that affect testosterone concentrations or metabolism

- Uncontrolled diabetes (screening glycated hemoglobin [HbA1c] ≥9%).

- Donated blood or blood products or experienced significant blood loss within 90 days
before dosing.

- Donated bone marrow within 6 months before dosing.

- History of drug or alcohol abuse in the last 6 months.

- Ingested St John's wort within 30 days of screening.