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

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ClinicalTrials.gov Identifier: NCT03335254
Recruitment Status : Terminated (Incomplete effect)
First Posted : November 7, 2017
Last Update Posted : August 15, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Hypogonadism Hypogonadism, Male Gonadal Disorders Endocrine System Diseases Testosterone Deficiency Drug: TSX-011 Phase 1 Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Study to Determine the Dose Response Pharmacokinetics of TSX-011 (Testosterone Undecanoate) in Hypogonadal Males
Actual Study Start Date : November 6, 2017
Actual Primary Completion Date : May 3, 2018
Actual Study Completion Date : May 3, 2018


Arm Intervention/treatment
Experimental: Period 1: Single Dose
Period 1. Ascending single-dose period: 190 mg TSX-011 (fed and fasted), 380 mg TSX-011 (fed), and 570 mg TSX-011 (fed).
Drug: TSX-011
TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.

Experimental: Period 2: Twice Daily Dose
380 mg TSX-011 twice daily dosing period of 15 days in fed conditions.
Drug: TSX-011
TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.

Experimental: Period 3, Day 16-25: Once Daily Dose

If Period 2 Day 8 total testosterone is >800 ng/dL, subjects randomized in a 1:1 ratio to receive:

  • Schedule A: 317 mg (TU) TSX-011 twice daily OR
  • Schedule B: 507 mg (TU) TSX-011 once daily.
Drug: TSX-011
TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.

Experimental: 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.

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.

If Period 2 Day 8 total testosterone is 500 to 800 ng/dL, inclusive, maintain 380 mg (TU) TSX-011 twice daily.

If Period 2 Day 8 total testosterone is >800 ng/dL, randomize subjects in a 1:1 ratio to receive:

  • Schedule A: 317 mg (TU) TSX-011 twice daily OR
  • Schedule B: 507 mg (TU) TSX-011 once daily.
Drug: TSX-011
TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.

Experimental: 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.

If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose of 507 mg TU daily.

If Period 3, Day 19 total testosterone is >800 ng/dL, decrease TSX-011 dose as follows: Dose adjust subjects on once-daily dosing from 507 mg TU daily to 380 mg TU daily.

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

Experimental: Period 3, Day 26-30: Twice Daily Dose

If Period 3 Day 19 total testosterone is >350 ng/dL and <500 ng/dL:

Dose adjust subjects on twice daily dosing as follows:

  • If dose is 570 mg TU twice daily, increase to 633 mg TU twice daily.
  • If dose is 443 mg TU twice daily, increase to 507 mg TU twice daily.
  • If dose is 380 mg TU twice daily, increase to 443 mg TU twice daily.
  • If dose is 317 mg TU twice daily, increase to 380 mg TU twice daily.

If Period 3 Day 19 total testosterone is 500 to 800 ng/dL inclusive, continue current dose twice daily.

If Period 3 Day 19 total testosterone is >800 ng/dL, decrease TSX-011 dose as follows:

For the twice-daily dosing group:

  • If dose is 570 mg TU twice daily, decrease to 507 mg TU twice daily.
  • If dose is 443 mg TU twice daily, decrease to 380 mg TU twice daily.
  • If dose is 380 mg TU twice daily, decrease to 317 mg TU twice daily.
  • If dose is 317 mg TU twice daily, decrease to 253 mg TU twice daily.
Drug: TSX-011
TSX-011 are capsules with Testosterone Undecanoate (prodrug for androgen testosterone) as the primary ingredient.

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




Primary Outcome Measures :
  1. Period 1: Percentage of responders based on measured total testosterone (Cmax). [ Time Frame: Up to 4 weeks (Period 1) ]
    TSX-011 responders are defined as study subjects who are able to achieve a Cmax testosterone > 350 ng/dL.

  2. Period 2: Percentage of responders based on measured total testosterone (Cavg). [ Time Frame: At 24 hour PK collection days - Day 15. ]
    TSX-011 responders are defined as study subjects who are able to achieve a Cavg testosterone > 350 ng/dL.

  3. Period 3: Percentage of responders based on measured total testosterone (Cavg). [ Time Frame: At 24 hour PK collection days - Day 30. ]
    TSX-011 responders are defined as study subjects who are able to achieve a Cavg testosterone > 350 ng/dL.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03335254


Locations
United States, California
California Clinical Trials
Glendale, California, United States, 91206
Sponsors and Collaborators
TesoRx Pharma, LLC
Investigators
Study Director: Michael Oefelein, MD TesoRx Pharma

Responsible Party: TesoRx Pharma, LLC
ClinicalTrials.gov Identifier: NCT03335254     History of Changes
Other Study ID Numbers: TT-018
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by TesoRx Pharma, LLC:
Hypogonadism
Testosterone
Testosterone undecanoate

Additional relevant MeSH terms:
Hypogonadism
Endocrine System Diseases
Gonadal Disorders
Eunuchism
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents