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

Phase 1

Terminated

• Conditions: Hypogonadism; Hypogonadism, Male; Gonadal Disorders; Endocrine System Diseases; Testosterone Deficiency
• Interventions: Drug: TSX-011

• Registration Number: NCT03335254
• Lead Sponsor: TesoRx Pharma, LLC

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2017-10-13
• Study First Submitted QC: 2017-11-02
• Study Start: 2017-11-06
• Study First Posted: 2017-11-07
• Primary Completion: 2018-05-03
• Study Completion: 2018-05-03
• Results First Submitted: 2019-03-04
• Status Verified: 2019-04
• Results First Submitted QC: 2019-04-22
• Last Update Submitted: 2019-04-22
• Results First Posted: 2019-05-16
• Last Update Posted: 2019-05-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 9

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose-Escalating Arm 4	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \<350 ng/dL, adjust dose to 570 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is \>800 ng/dL, decrease to 507 mg TU twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 5	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 443 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Thrice Daily Dose If Period 3 Day 19 total testosterone is \<350 ng/dL, dose adjust subjects to 570 mg TSX-011 (TU) dosing thrice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 10	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is 500 to 800 ng/dL, inclusive, maintain 380 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is ≥350 ng/dL and \<500 ng/dL, increase dose to 443 mg TU twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 20	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Once Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 507 mg (TU) TSX-011 once daily. Period 3, Day 26-30: Once Daily Dose If Period 3, Day 19 total testosterone is \>800 ng/dL, decrease dose to 380 mg TU daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 2	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \<350 ng/dL, adjust dose to 570 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 633 mg TU twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 11	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is 500 to 800 ng/dL, inclusive, maintain 380 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose 380 mg (TU) TSX-011 twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 1	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \<350 ng/dL, adjust dose to 570 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Thrice Daily Dose If Period 3 Day 19 total testosterone is \<350 ng/dL, dose adjust subjects to 570 mg TSX-011 (TU) dosing thrice daily. Assigned Intervention: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 3	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \<350 ng/dL, adjust dose to 570 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose 570 mg (TU) TSX-011 twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 6	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 443 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 507 mg TU twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 7	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 443 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose 443 mg (TU) TSX-011 twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 8	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is ≥350 ng/dL and \<500 ng/dL, adjust dose to 443 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is \>800 ng/dL, decrease dose to 380 mg TU twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 9	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is 500 to 800 ng/dL, inclusive, maintain 380 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Thrice Daily Dose If Period 3 Day 19 total testosterone is \<350 ng/dL, dose adjust subjects to 570 mg TSX-011 (TU) dosing thrice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 13	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 317 mg (TU) TSX-011 twice daily Period 3, Day 26-30: Thrice Daily Dose If Period 3 Day 19 total testosterone is \<350 ng/dL, dose adjust subjects to 570 mg TSX-011 (TU) dosing thrice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 16	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 317 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is \>800 ng/dL, decrease dose to 253 mg TU twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 18	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Once Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 507 mg (TU) TSX-011 once daily. Period 3, Day 26-30: Once Daily Dose If Period 3 Day 19 total testosterone is ≥350 ng/dL and \<500 ng/dL, dose adjust subjects on once-daily dosing from 507 mg TU daily to 570 mg TU daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 19	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Once Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 507 mg (TU) TSX-011 once daily. Period 3, Day 26-30: Once Daily Dose If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose of 507 mg TU daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 12	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is 500 to 800 ng/dL, inclusive, maintain 380 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is \>800 ng/dL, decrease TSX-011 dose to 317 mg TU twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 14	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 317 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is ≥350 ng/dL and \<500 ng/dL, increase dose to 380 mg TU twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 15	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Twice Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 317 mg (TU) TSX-011 twice daily. Period 3, Day 26-30: Twice Daily Dose If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose 317 mg (TU) TSX-011 twice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.
Dose-Escalating Arm 17	TSX-011	Period 1: Single Dose Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed). Period 2: Twice Daily Dose 380 mg TSX-011 twice daily dosing period of 15 days in fed conditions. Period 3, Day 16-25: Once Daily Dose If Period 2 Day 8 total testosterone is \>800 ng/dL, randomize half subjects to receive 507 mg (TU) TSX-011 once daily. Period 3, Day 26-30: Thrice Daily Dose If Period 3 Day 19 total testosterone is \<350 ng/dL, dose adjust subjects to 570 mg TSX-011 (TU) dosing thrice daily. TSX-011: TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.

Primary Outcome Measures

Name	Time	Method
Percentage of Responders Based on Measured Total Testosterone (Cavg).	Period 1: Up to 13 days. Period 2: 15 days. Period 3: 15 days.	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.

Trial Locations

Locations (1)

California Clinical Trials; 🇺🇸 Glendale, California, United States