Hypogonadism
Conditions
Keywords
hypogonadism, Gonadal Disorders, Endocrine System Diseases, Testosterone, Testosterone enanthate, Testosterone undecanoate, Testosterone 17 beta-cypionate, Methyltestosterone, Androgens, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Pharmacologic Actions, Therapeutic Uses, Anabolic Agents
Brief summary
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.
Interventions
DRUGTSX-002
TSX-002 are capsules with testosterone as the active ingredient.
Sponsors
TesoRx Pharma, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 15 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 15 days | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cavg 0-24 Hrs (ng/dL) After 120 mg Dose | 24 hrs | 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. |
| AUC 0-24 Hrs After 120 mg Dose of TSX-002 | 24 hrs | 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. |
Countries
United States
Participant flow
Recruitment details
130 subjects were recruited at 1 center in the US from October 2012 to May 2014. The study was designed with 4 parts, including 9 different dosages of the investigational drug.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: 120 mg BID Oral TSX-002 120 mg BID (total dose = 240 mg/day) for a duration of 15 days
TSX-002: TSX-002 are capsules with testosterone as the active ingredient. | 17 |
| Part 1: 240 mg BID Oral TSX-002 240 mg BID (total dose = 480 mg/day) for a duration of 15 days
TSX-002: TSX-002 are capsules with testosterone as the active ingredient. | 17 |
| 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
TSX-002: TSX-002 are capsules with testosterone as the active ingredient. | 17 |
| 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.
TSX-002: TSX-002 are capsules with testosterone as the active ingredient. | 4 |
| 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.
TSX-002: TSX-002 are capsules with testosterone as the active ingredient. | 5 |
| 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.
TSX-002: TSX-002 are capsules with testosterone as the active ingredient. | 5 |
| 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
TSX-002: TSX-002 are capsules with testosterone as the active ingredient. | 17 |
| 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
TSX-002: TSX-002 are capsules with testosterone as the active ingredient. | 16 |
| Part 4 Cohort 3: 180 mg QD Oral TSX-002 180 mg once daily (QD) for 15 days
TSX-002: TSX-002 are capsules with testosterone as the active ingredient. | 16 |
| Part 4 Cohort 4: 120 mg BID Oral TSX-002 120 mg BID for 15 days
TSX-002: TSX-002 are capsules with testosterone as the active ingredient. | 16 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 (Duration of 15 Days) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 4-Treatment 1 (Duration of 15 Days) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 4-Treatment 2 (Duration of 15 Days) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 4-Treatment 2 (Duration of 15 Days) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1: 120 mg BID | Part 1: 240 mg BID | Part 2: 120 mg BID | Part 3: A-B-C 120 mg QD | Part 3: B-C-A 120 mg QD | Part 3: C-A-B 120 mg QD | Part 4 Cohort 1: 60 mg BID/ 60 mg TID | Part 4 Cohort 2: 90 mg BID/ 90 mg TID | Part 4 Cohort 3: 180 mg QD | Part 4 Cohort 4: 120 mg BID | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 50-64 years | 11 participants | 11 participants | 5 participants | 1 participants | 4 participants | 4 participants | 9 participants | 8 participants | 7 participants | 9 participants | 69 participants |
| Age, Customized <50 years | 2 participants | 4 participants | 8 participants | 1 participants | 1 participants | 0 participants | 4 participants | 4 participants | 9 participants | 5 participants | 38 participants |
| Age, Customized 65-74 years | 3 participants | 2 participants | 3 participants | 1 participants | 0 participants | 1 participants | 3 participants | 4 participants | 0 participants | 2 participants | 19 participants |
| Age, Customized 75 years or older | 1 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 4 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 1 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 12 Participants | 17 Participants | 3 Participants | 2 Participants | 2 Participants | 10 Participants | 12 Participants | 13 Participants | 12 Participants | 96 Participants |
| Region of Enrollment United States | 17 participants | 17 participants | 17 participants | 4 participants | 5 participants | 5 participants | 17 participants | 16 participants | 16 participants | 16 participants | 130 participants |
| Sex/Gender, Customized Male | 17 participants | 17 participants | 17 participants | 4 participants | 5 participants | 5 participants | 17 participants | 16 participants | 16 participants | 16 participants | 130 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 17 | 8 / 17 | 6 / 17 | 0 / 4 | 2 / 5 | 2 / 5 | 3 / 17 | 3 / 17 | 0 / 16 | 2 / 16 | 6 / 16 | 3 / 16 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 0 / 17 | 0 / 4 | 0 / 5 | 0 / 5 | 0 / 17 | 0 / 17 | 0 / 16 | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
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.
Time frame: 15 days
Population: All efficacy analyses were conducted based on the modified intent-to-treat (MITT) analysis population, comprised of all randomized subjects who receive at least 1 dose of study drug and have at least 1 post-baseline measurement of total serum testosterone.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: 120 mg BID | 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 | 59 percentage of participants |
| Part 1: 240 mg BID | 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 | 31 percentage of participants |
| Part 2: 120 mg BID | 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 | 35 percentage of participants |
| Part 4 Cohort 1: 60 mg BID | 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 | 41 percentage of participants |
| Part 4 Cohort 1: 60 mg TID | 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 | 53 percentage of participants |
| Part 4 Cohort 2: 90 mg BID | 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 | 19 percentage of participants |
| Part 4 Cohort 2: 90 mg TID | 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 | 20 percentage of participants |
| Part 4 Cohort 3: 180 mg QD | 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 | 31 percentage of participants |
| Part 4 Cohort 4: 120 mg BID | 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 | 27 percentage of participants |
Secondary
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.
Time frame: 15 days
Population: All efficacy analyses were conducted based on the modified intent-to-treat (MITT) analysis population, comprised of all randomized subjects who receive at least 1 dose of study drug and have at least 1 post-baseline measurement of total serum testosterone.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: 120 mg BID | 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 | Percentage of subjects with Cmax ≤ 1500 ng/dL afte | 100 percentage of subjects |
| Part 1: 120 mg BID | 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 | Percentage of subjects with Cmax ≥ 1800 and ≤ 2500 | 0 percentage of subjects |
| Part 1: 120 mg BID | 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 | Percentage of subjects with Cmax > 2500 ng/dL afte | 0 percentage of subjects |
| Part 1: 240 mg BID | 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 | Percentage of subjects with Cmax > 2500 ng/dL afte | 0 percentage of subjects |
| Part 1: 240 mg BID | 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 | Percentage of subjects with Cmax ≤ 1500 ng/dL afte | 100 percentage of subjects |
| Part 1: 240 mg BID | 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 | Percentage of subjects with Cmax ≥ 1800 and ≤ 2500 | 0 percentage of subjects |
| Part 2: 120 mg BID | 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 | Percentage of subjects with Cmax > 2500 ng/dL afte | 0 percentage of subjects |
| Part 2: 120 mg BID | 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 | Percentage of subjects with Cmax ≤ 1500 ng/dL afte | 94.1 percentage of subjects |
| Part 2: 120 mg BID | 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 | Percentage of subjects with Cmax ≥ 1800 and ≤ 2500 | 0 percentage of subjects |
| Part 4 Cohort 1: 60 mg BID | 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 | Percentage of subjects with Cmax > 2500 ng/dL afte | 0 percentage of subjects |
| Part 4 Cohort 1: 60 mg BID | 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 | Percentage of subjects with Cmax ≤ 1500 ng/dL afte | 100 percentage of subjects |
| Part 4 Cohort 1: 60 mg BID | 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 | Percentage of subjects with Cmax ≥ 1800 and ≤ 2500 | 0 percentage of subjects |
| Part 4 Cohort 1: 60 mg TID | 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 | Percentage of subjects with Cmax > 2500 ng/dL afte | 0 percentage of subjects |
| Part 4 Cohort 1: 60 mg TID | 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 | Percentage of subjects with Cmax ≥ 1800 and ≤ 2500 | 0 percentage of subjects |
| Part 4 Cohort 1: 60 mg TID | 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 | Percentage of subjects with Cmax ≤ 1500 ng/dL afte | 100 percentage of subjects |
| Part 4 Cohort 2: 90 mg BID | 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 | Percentage of subjects with Cmax ≤ 1500 ng/dL afte | 100 percentage of subjects |
| Part 4 Cohort 2: 90 mg BID | 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 | Percentage of subjects with Cmax ≥ 1800 and ≤ 2500 | 0 percentage of subjects |
| Part 4 Cohort 2: 90 mg BID | 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 | Percentage of subjects with Cmax > 2500 ng/dL afte | 0 percentage of subjects |
| Part 4 Cohort 2: 90 mg TID | 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 | Percentage of subjects with Cmax ≥ 1800 and ≤ 2500 | 0 percentage of subjects |
| Part 4 Cohort 2: 90 mg TID | 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 | Percentage of subjects with Cmax ≤ 1500 ng/dL afte | 100 percentage of subjects |
| Part 4 Cohort 2: 90 mg TID | 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 | Percentage of subjects with Cmax > 2500 ng/dL afte | 0 percentage of subjects |
| Part 4 Cohort 3: 180 mg QD | 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 | Percentage of subjects with Cmax ≥ 1800 and ≤ 2500 | 0 percentage of subjects |
| Part 4 Cohort 3: 180 mg QD | 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 | Percentage of subjects with Cmax ≤ 1500 ng/dL afte | 100 percentage of subjects |
| Part 4 Cohort 3: 180 mg QD | 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 | Percentage of subjects with Cmax > 2500 ng/dL afte | 0 percentage of subjects |
| Part 4 Cohort 4: 120 mg BID | 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 | Percentage of subjects with Cmax ≤ 1500 ng/dL afte | 93.75 percentage of subjects |
| Part 4 Cohort 4: 120 mg BID | 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 | Percentage of subjects with Cmax ≥ 1800 and ≤ 2500 | 6.25 percentage of subjects |
| Part 4 Cohort 4: 120 mg BID | 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 | Percentage of subjects with Cmax > 2500 ng/dL afte | 0 percentage of subjects |
Other Pre-specified
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.
Time frame: 24 hrs
Population: All subjects that received 120 mg TSX-002 under defined Treatment conditions (timing of high-calorie, high-fat meal).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Part 1: 120 mg BID | AUC 0-24 Hrs After 120 mg Dose of TSX-002 | 1941 hr×ng/dL | Standard Deviation 1198 |
| Part 1: 240 mg BID | AUC 0-24 Hrs After 120 mg Dose of TSX-002 | 2117 hr×ng/dL | Standard Deviation 1351 |
| Part 2: 120 mg BID | AUC 0-24 Hrs After 120 mg Dose of TSX-002 | 1516 hr×ng/dL | Standard Deviation 1217 |
Other Pre-specified
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.
Time frame: 24 hrs
Population: All subjects that received 120 mg TSX-002 under defined Treatment conditions (timing of high-calorie, high-fat meal).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: 120 mg BID | Cavg 0-24 Hrs (ng/dL) After 120 mg Dose | 296 ng/dL | Standard Deviation 108 |
| Part 1: 240 mg BID | Cavg 0-24 Hrs (ng/dL) After 120 mg Dose | 297 ng/dL | Standard Deviation 75 |
| Part 2: 120 mg BID | Cavg 0-24 Hrs (ng/dL) After 120 mg Dose | 273 ng/dL | Standard Deviation 109 |