A Phase 1/2a Study to Determine the Dose Response Pharmacokinetics of TSX-011 (Testosterone Undecanoate) in Hypogonadal Males
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Percentage of Responders Based on Measured Total Testosterone (Cavg).
研究概览
简要总结
This will be a phase 1/2a, open-label, single-center study with 3 periods. The aims of the study are to:
- evaluate the dose-response curve following ascending single doses of TSX-011;
- confirm optimum dosing conditions;
- evaluate the efficacy of single or multiple daily adaptive dosing; and
- evaluate the safety and tolerability of TSX-011.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Testosterone level <350 ng/dL, 10 am [± 2 hour] sample.
- •Body mass index (BMI) <35.0 kg/m2 and weight ≥50 kg
排除标准
- •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) ≥
- •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
- •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.
研究组 & 干预措施
Dose-Escalating Arm 1
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 2
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 3
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 4
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 5
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 6
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 7
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 8
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 9
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 10
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 11
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 12
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 13
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 14
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 15
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 16
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 17
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 18
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 19
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.
干预措施: TSX-011 (Drug)
Dose-Escalating Arm 20
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.
干预措施: TSX-011 (Drug)
结局指标
主要结局
Percentage of Responders Based on Measured Total Testosterone (Cavg).
时间窗: 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.
次要结局
未报告次要终点