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

Hypogonadism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03335254
• Other study ID #: TT-018
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 6, 2017
• Est. completion date: May 3, 2018

Study information

• Verified date: April 2019
• Source: TesoRx Pharma, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: May 3, 2018
• Est. primary completion date: May 3, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Endocrine System Diseases
• Gonadal Disorders
• Hypogonadism
• Hypogonadism, Male
• Testosterone Deficiency

Intervention

Drug:
• TSX-011
TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.

Locations

Country	Name	City	State
United States	California Clinical Trials	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
TesoRx Pharma, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Responders Based on Measured Total Testosterone (Cavg).	TSX-011 responders are defined as study subjects who are able to achieve a Cavg serum total testosterone > 350 ng/dL. The percentage of responders is recorded for each treatment group within each period.	Period 1: Up to 13 days. Period 2: 15 days. Period 3: 15 days.