Oral Testosterone for the Treatment of Hypogonadism

A Phase 2, Randomized, Double-blind, Dose Response Study of Oral Testosterone in Subjects With Hypogonadism

Low testosterone is a condition that occurs when the body is unable to produce sufficient quantities of testosterone. The medical name for low testosterone is hypogonadism. Hypogonadism can be caused by many factors. Symptoms include: decrease in libido, lack of energy and mood swings. The goal of testosterone replacement therapy is to return testosterone levels to the normal range and relieve symptoms.

The purpose of this study is to evaluate the ability of TSX-002, which is testosterone provided in easy to swallow capsules, to maintain serum (blood) testosterone levels within the normal range in hypogonadal men. This will be determined by blood sampling at specified times during the study. The study is also intended to evaluate the tolerability of TSX-002, which will be taken orally twice per day for 15 days. In addition, the study is intended to determine a dosing regimen(s) that achieves testosterone levels within the normal range. Related Outcome Measures will be reported for Parts 1, 2, and 4.

A portion of the study (Part 3) to also assess the effect of a high-calorie, high-fat meal on the single dose pharmacokinetic exposure of TSX-002. Related outcome measures to be reported for Part 3.

Study Overview

• Status: Completed
• Conditions: Hypogonadism
• Intervention / Treatment: Drug: TSX-002

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Urology Group of Southern California

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Prior documentation of a diagnosis of hypogonadism as evidenced by a screening serum testosterone < 300 ng/dL (based on the average of 2 morning samples taken at least 1 week apart)
• Men over the age of 18 years with a body mass index (BMI) < 39.0 kg/m2 and weighing ≥ 55 kg
• Hemoglobin levels at screening and baseline > 12.5 g/dL
• Testosterone treatment not contraindicated
• No evidence of suspected reversible hypogonadism
• Willing to abstain from current treatment for hypogonadism in accordance with approved labeling to facilitate an appropriate washout period before study participation (for nondepot formulations of testosterone only)
• Understands the requirements of the study and voluntarily consents to participate in the study

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: 120 mg BID; Oral TSX-002 120 mg BID (total dose = 240 mg/day) for a duration of 15 days	Drug: TSX-002; TSX-002 are capsules with testosterone as the active ingredient.; Other Names: Testosterone
Experimental: Part 1: 240 mg BID; Oral TSX-002 240 mg BID (total dose = 480 mg/day) for a duration of 15 days	Drug: TSX-002; TSX-002 are capsules with testosterone as the active ingredient.; Other Names: Testosterone
Experimental: Part 2: 120 mg BID; Single cohort, open-label, nonrandomized oral TSX 002 120 mg BID (total dose = 240 mg/day) for a duration of 15 days	Drug: TSX-002; TSX-002 are capsules with testosterone as the active ingredient.; Other Names: Testosterone
Experimental: Part 3: A-B-C 120 mg QD; Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C.; Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.; Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.; Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.	Drug: TSX-002; TSX-002 are capsules with testosterone as the active ingredient.; Other Names: Testosterone
Experimental: Part 3: B-C-A 120 mg QD; Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C.; Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.; Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.; Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.	Drug: TSX-002; TSX-002 are capsules with testosterone as the active ingredient.; Other Names: Testosterone
Experimental: Part 3: C-A-B 120 mg QD; Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C.; Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.; Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.; Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.	Drug: TSX-002; TSX-002 are capsules with testosterone as the active ingredient.; Other Names: Testosterone
Experimental: Part 4 Cohort 1: 60 mg BID/ 60 mg TID; Oral TSX-002 60 mg BID for 15 days then 60 mg TID for 15 days	Drug: TSX-002; TSX-002 are capsules with testosterone as the active ingredient.; Other Names: Testosterone
Experimental: Part 4 Cohort 2: 90 mg BID/ 90 mg TID; Oral TSX-002 90 mg BID for 15 days then 90 mg TID for 15 days	Drug: TSX-002; TSX-002 are capsules with testosterone as the active ingredient.; Other Names: Testosterone
Experimental: Part 4 Cohort 3: 180 mg QD; Oral TSX-002 180 mg once daily (QD) for 15 days	Drug: TSX-002; TSX-002 are capsules with testosterone as the active ingredient.; Other Names: Testosterone
Experimental: Part 4 Cohort 4: 120 mg BID; Oral TSX-002 120 mg BID for 15 days	Drug: TSX-002; TSX-002 are capsules with testosterone as the active ingredient.; Other Names: Testosterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving a 24 Hour Average Total Serum Testosterone Concentration (Cavg,0-24h) in the Range of 300 to 1050 ng/dL After 15 Days of Treatment With TSX-002	Percentage of subjects achieving a 24-hour average total serum testosterone concentration (Cavg,0-24h) in the range of 300 to 1050 ng/dL after 15 days of treatment with TSX-002. PK samples taken at 0 ,2 ,4, 5 ,6, 7, 9, 12, 14, 16, 17, 18, 21, 24 hours post-dose after 15 days of treatment for Part 1. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 16, 17, 18, 19, 20, 21, 22, 24 hours post-dose after 15 days of treatment for Part 2. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8 ,12, 13, 14, 15, 16, 17, 18, 20, 24 hours post-dose after 15 days of treatment for Part 4.	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Cmax ≤ 1500 ng/dL After 15 Days of Treatment 2. Percentage of Subjects With Cmax ≥ 1800 and ≤ 2500 ng/dL After 15 Days of BID Treatment 3. Percentage of Subjects With Cmax > 2500 ng/dL After 15 Days of BID Treatment	Cmax. PK samples taken at 0, 2, 4, 5, 6, 7, 9, 12, 14, 16, 17, 18, 21, 24 hours post-dose after 15 days of treatment for Part 1. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 16, 17, 18, 19, 20, 21, 22, 24 hours post-dose after 15 days of treatment for Part 2. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 13, 14, 15, 16, 17,18, 20, 24 hours post-dose after 15 days of treatment for Part 4.	15 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cavg 0-24 Hrs (ng/dL) After 120 mg Dose	PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24 hours post-dose after 1 day of treatment for Part 3. Mean of Cavg values from all time points for 14 subjects.	24 hrs
AUC 0-24 Hrs After 120 mg Dose of TSX-002	AUC 0-24 hrs with PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24 hours post-dose after 1 day of treatment for Part 3.	24 hrs

Collaborators and Investigators

• Sponsor: TesoRx Pharma, LLC
• Investigators: Principal Investigator: John Kowalczyk, DO, FACOS, Urology Group of Southern California

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: October 25, 2012
• First Submitted That Met QC Criteria: October 26, 2012
• First Posted (Estimate): October 30, 2012

Study Record Updates

• Last Update Posted (Estimate): December 15, 2015
• Last Update Submitted That Met QC Criteria: December 14, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: hypogonadism; Physiological Effects of Drugs; Pharmacologic Actions; Therapeutic Uses; Endocrine System Diseases; Testosterone; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone enanthate; Gonadal Disorders; Testosterone undecanoate; Testosterone 17 beta-cypionate; Methyltestosterone; Anabolic Agents
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: TT-002