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

NCT03335254 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: TT-018
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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. 1.evaluate the dose-response curve following ascending single doses of TSX-011;
2. 2.confirm optimum dosing conditions;
3. 3.evaluate the efficacy of single or multiple daily adaptive dosing; and
4. 4.evaluate the safety and tolerability of TSX-011.

Conditions

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

Keywords

Hypogonadism; Testosterone; Testosterone undecanoate

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (20)

Dose-Escalating Arm 1

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 2

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 3

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 4

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 5

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 6

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 7

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 8

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 9

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 10

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 11

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 12

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 13

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 14

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 15

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 16

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 17

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 18

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 19

EXPERIMENTAL

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.

Drug: TSX-011

Dose-Escalating Arm 20

EXPERIMENTAL

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.

Drug: TSX-011

Interventions

TSX-011 DRUG

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

Dose-Escalating Arm 1; Dose-Escalating Arm 10; Dose-Escalating Arm 11; Dose-Escalating Arm 12; Dose-Escalating Arm 13; Dose-Escalating Arm 14; Dose-Escalating Arm 15; Dose-Escalating Arm 16; Dose-Escalating Arm 17; Dose-Escalating Arm 18; Dose-Escalating Arm 19; Dose-Escalating Arm 2; Dose-Escalating Arm 20; Dose-Escalating Arm 3; Dose-Escalating Arm 4; Dose-Escalating Arm 5; Dose-Escalating Arm 6; Dose-Escalating Arm 7; Dose-Escalating Arm 8; Dose-Escalating Arm 9

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Testosterone level \<350 ng/dL, 10 am \[± 2 hour\] sample.
• Body mass index (BMI) \<35.0 kg/m2 and weight ≥50 kg

You may not qualify if:

• 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:
• 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).
• Known or suspected carcinoma (or history of carcinoma) of the breast.
• Liver disease defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2 × upper limit of normal (ULN) or bilirubin \>2 × ULN.
• Active deep vein thrombosis or thromboembolic disorder, or a documented history of these conditions.
• Untreated sleep apnea.
• Hematocrit \>50%.
• 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

Sponsors & Collaborators

• TesoRx Pharma, LLC: lead

Study Sites (1)

California Clinical Trials

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

Hypogonadism; Eunuchism; Gonadal Disorders; Endocrine System Diseases

Results Point of Contact

• Title: Michael Oefelein, MD, Chief Medical Officer
• Organization: TesoRx Pharma, LLC

karl@tesorx.com

909-595-0500

Study Officials

• Michael Oefelein, MD

  TesoRx Pharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants receive identical dosing for Period 1 and Period 2. Beginning with Period 3 subjects are assigned to one of several doses based on dose adjustments. Period 3 dosing groups are run in parallel for the duration of the study.

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: November 7, 2017
• Study Start: November 6, 2017
• Primary Completion: May 3, 2018
• Study Completion: May 3, 2018
• Last Updated: May 16, 2019
• Results First Posted: May 16, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)