Cocaine Use Disorder, Healthy Volunteers, Substance Use Disorders
Conditions
Keywords
drug addiction, cocaine use disorder, cocaine dependance, TMP-301, cocaine use, CUD, drug abuse
Brief summary
A PHASE 1, RANDOMIZED, PLACEBO CONTROLLED, MULTIPLE ASCENDING DOSE (MAD) STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF TMP-301 IN HEALTHY SUBJECTS.
Detailed description
This study will be a randomized, double-blind, placebo controlled, fixed sequence, MAD study. The study will be conducted in a single clinical research unit (CRU). The study will consist of up to 4 cohorts. Subjects will only participate in 1 cohort. Screening will occur within approximately 28 days prior to the first scheduled study drug administration. Subjects who meet all inclusion criteria and none of the exclusion criteria and who consent to participation will be admitted to the CRU for baseline evaluations prior to dosing. Subjects will be fasted overnight for 10 hours prior to the morning dose, followed by a 2 hour fast. Subjects are fasted for 2 hours prior to dosing and 2 hours following the evening dose for the cohort 1 (50 mg bid). Subjects will be discharged from the CRU on Day 18. Subjects will return to the CRU on Day 25 for a follow-up visit and EOS procedures. Caffeine (100 mg) will be included as probe CYP1A2 substrate in cohort 2 and subsequent cohorts. The maximum duration of subject participation, including Screening, will be approximately 53 days. Subjects who terminate the study early will perform follow-up procedures at the time of Early Termination.
Interventions
DRUGCohort 4 - TMP-301
25 mg QD Fed
DRUGCohort 1 - TMP-301
50 mg BID Fasted
DRUGPlacebo
Multiple ascending dose comparator
DRUGCohort 2 - TMP-301
50 mg QD Fasted
DRUGCohort 3 - TMP-301
50 mg QD Fed
Sponsors
National Institute on Drug Abuse (NIDA)
Tempero Bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blind
Intervention model description
sequential assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated informed consent form (ICF) 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Healthy adult male or female 4. If male, meets one of the following criteria: a) Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the follow-up visit. An acceptable method of contraception includes one of the following: Abstinence from heterosexual intercourse, or Male condom with spermicide or male condom with a vaginal spermicide (gel, foam, or suppository); or b) Is unable to procreate; defined as surgically sterile (ie, has undergone a vasectomy at least 180 days prior to the first study drug administration) 5. If female, meets one of the following criteria: (1) Physiological postmenopausal status, defined as the following: a) absence of menses for at least 12 months prior to the first study drug administration (without an alternative medical condition); and b) Follicle stimulating hormone (FSH) levels ≥ 40 mIU/mL at Screening; Or (2) Surgical postmenopausal status, defined as the following: a) bilateral oophorectomy, salpingectomy, or tubal ligation; hysterectomy 6. Aged at least 18 years but not older than 59 years, inclusive, at the time of informed consent 7. Body mass index (BMI) within 18.5 kg/m2 to 32.0 kg/m2, inclusively 8. Minimum body weight of at least 50.0 kg 9. Non- or ex smoker (An ex smoker is defined as someone who completely stopped using nicotine products for at least 90 days prior to the first study drug administration) 10. Must be willing to abstain from drinking coffee or caffeine containing beverages during the study, except where part of the study procedures 11. Has supine blood pressure and pulse rate within the following ranges after 5 minutes rest: systolic blood pressure 90 to 140 mmHg, diastolic blood pressure 50 to 90 mmHg, and pulse rate 45 to 90 bpm at Screening and on Day -1 12. Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by an Investigator 13. Has clinical laboratory test results within the reference ranges of the testing laboratory, with the exception of results outside the reference ranges that are deemed not clinically significant by the Investigator (or designee) at Screening and check-in \*
Exclusion criteria
1. Female who is lactating 2. Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration 3. Female using the following systemic contraceptives: oral, patch or vaginal ring, in the 28 days prior to the first study drug administration and during the study 4. Female using hormone replacement therapy in the 28 days prior to the first study drug administration and during the study 5. Female using the following systemic contraceptives: injections or implant, or hormone releasing intrauterine device in the 13 weeks prior to the first study drug administration and during the study 6. Drinking excessive amounts of tea, coffee, chocolate, and/or beverage or eating food containing caffeine (\> 2 cups/day) 7. Use of tobacco or nicotine containing products (including but not limited to; cigarettes, electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum) within 90 days prior to the first study drug administration and the inability to abstain from nicotine containing products until the follow-up visit. 8. Past or current history of any mental, behavioral, or neurodevelopmental disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) or significant risk of developing a psychosis (assessed by PRIME screen) or a personal history of psychotic symptoms (hallucinations or delusions) with or without a formal psychiatric diagnosis. Subjects with family history of significant mental, behavioral, or neurodevelopmental disorders unless determined by the Investigator (or designee) and agreed by the Medical Monitor to be non-clinically significant (NCS) will be excluded. 9. History or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, gastrointestinal, neurological, respiratory, or endocrine disorder, unless determined by the Investigator (or designee) and agreed by the Medical Monitor to be NCS 10. Active or history of cardiovascular or cerebrovascular disease, including hypertension, angina, ischemic heart disease, transient ischemic attacks, bundle branch block, evidence of myocardial ischemia, stroke, and peripheral arterial disease sufficient to cause symptoms and/or require therapy to maintain stable status 11. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) 12. Active neoplastic disease or history of any neoplastic disease within 5 years of Screening (except for basal or squamous cell carcinoma of the skin or carcinoma in situ that has been definitely treated with standard of care) 13. Active infection (eg, sepsis, pneumonia, abscess) or a serious infection (eg, resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks prior to dosing 14. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed) 15. Any of the following at Screening and/or prior to the first study drug administration: 1. QT interval corrected for heart rate using Fridericia's method (QTcF) \> 450 ms confirmed by repeat measurement 2. QRS duration \> 110 ms confirmed by confirmed by repeat measurement 3. PR interval \> 220 ms confirmed by repeat measurement 4. Findings which would make QTc measurements difficult or QTc data uninterpretable 5. History of additional risk factors for torsades de pointe (eg, heart failure, hypokalemia, family history of long QT syndrome) 16. Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic) 17. Positive test result for alcohol, cotinine, and/or drugs of abuse at Screening or prior to the first drug administration 18. Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus tests 19. Any other clinically significant abnormalities in laboratory test results at Screening that would, in the opinion of an Investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data 20. Intake of an IP in the 28 days prior to the first study drug administration 21. Use of any prescription drugs in the 28 days prior to the first study drug administration, that in the opinion of an Investigator would put into question the status of the participant as healthy 22. Use of St. John's wort in the 28 days prior to the first study drug administration and during the study 23. Consumption of any foods or beverages which alter CYP1A2 activity, e.g., barbecued food or cruciferous vegetables, such as broccoli and cauliflower, within 14 days prior to (first) check-in (a list of prohibited foods will be provided to subjects) 24. Consumption of any foods or beverages containing Seville-type oranges, grapefruit, or poppy seeds within 7 days prior to (first) check-in 25. Receipt of blood products within 2 months prior to check-in 26. Donation of 1 unit of blood to American Red Cross or equivalent organization or donation of over 500 mL of blood in the 56 days prior to the first study drug administration 27. Donation of plasma in the 7 days prior to the first study drug administration 28. Poor peripheral venous access 29. History or significant hypersensitivity to TMP301 or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs 30. Subjects who, in the opinion of the Investigator (or designee; including input from subjects' general practitioner, as applicable), should not participate in this study 31. Subject hospitalized for any reason in a period of 30 days before the start of the study 32. Subjects who are investigational site staff members or directly involved in the conduct of the study and their family members or subjects who are employed by the Sponsor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-Emergent Adverse Events (Safety and Tolerability) | Within each cohort from screening to end of the follow up period up to 25 days | Occurence of Adverse Events, spontaneously reported and identified through clinical laboratory tests, vital sign measurements, ECG, physical exams and psychiatric assessments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Plasma Area Under the Curve (AUC) 0-24 Hours After First Dose of TMP-301 | Day 1 | — |
| Maximum Plasma Concentration (Cmax) of TMP-301 | Day 1 | — |
| Time to Maximum Plasma Concentration (Tmax) of TMP-301 | Day 1 | — |
| Plasma Concentration of TMP-301 at 12 Hours After First Dose (C12) | Day 1 | — |
| Plasma Concentration of TMP-301 at 24 Hours After First Dose (C24) | Day 1 | — |
| Maximum Plasma Concentration (Cmax) of TMP-301 at Steady State | Day 14 | — |
| Average Plasma Concentration of TMP-301 at 12 Hours After Last Dose (C12) | Day 14 | — |
| To Evaluate the Plasma Area Under the Curve (AUC) 0-12 Hours After First Dose of TMP-301 | Day 1 | 0-12 hours post-dose on Day 1, twice daily dosing |
| Minimum Drug Concentration (Cmin) of TMP-301 at Steady State | Day 14 | — |
| Area Under the Curve (Exposure) at Steady-state( AUC0_tau,ss), Over the Dosing Interval. | Day 14 | — |
| Plasma Concentration of TMP-301 at 24 Hours After Last Dose at Steady State (C24, ss) | Day 14 | — |
| Terminal Half-life (T1/2) of TMP-301 | Day 14 | — |
| Apparent Total Plasma Clearance of TMP-301 After Extravascular Administration (CL/F) | Day 14 | — |
| Apparent Volume of Distribution of TMP-301 at Steady State (Vz/F) | Day 14 | — |
| Time to Maximum Plasma Concentration (Tmax) of TMP-301 at Steady State | Day 14 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - Active TMP-301 50 mg BID Fasted | 5 |
| Cohort 2 - Active TMP-301 50 mg QD Fasted | 6 |
| Cohort 3 - Active TMP-301 50 mg QD Fed | 6 |
| Cohort 4 - Active TMP-301 25 mg QD Fed | 6 |
| Placebo Placebo: Multiple ascending dose comparator | 7 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Protocol-Specified Withdrawal | 5 | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 - Active TMP-301 | Total | Placebo | Cohort 4 - Active TMP-301 | Cohort 3 - Active TMP-301 | Cohort 2 - Active TMP-301 |
|---|---|---|---|---|---|---|
| Age, Continuous | 36.6 years STANDARD_DEVIATION 8.17 | 40.1 years STANDARD_DEVIATION 10.21 | 38.1 years STANDARD_DEVIATION 8.51 | 32.0 years STANDARD_DEVIATION 7.18 | 45.7 years STANDARD_DEVIATION 10.42 | 47.8 years STANDARD_DEVIATION 9.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 26 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 10 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 16 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 5 participants | 30 participants | 7 participants | 6 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 0 Participants | 5 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 25 Participants | 5 Participants | 6 Participants | 4 Participants | 5 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 4 / 5 | 6 / 6 | 6 / 6 | 2 / 6 | 2 / 7 |
| serious Total, serious adverse events | 1 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 |
Outcome results
Primary
Number of Treatment-Emergent Adverse Events (Safety and Tolerability)
Occurence of Adverse Events, spontaneously reported and identified through clinical laboratory tests, vital sign measurements, ECG, physical exams and psychiatric assessments.
Time frame: Within each cohort from screening to end of the follow up period up to 25 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 - Active TMP-301 | Number of Treatment-Emergent Adverse Events (Safety and Tolerability) | 34 Number of TEAEs |
| Cohort 2 - Active TMP-301 | Number of Treatment-Emergent Adverse Events (Safety and Tolerability) | 54 Number of TEAEs |
| Cohort 3 - Active TMP-301 | Number of Treatment-Emergent Adverse Events (Safety and Tolerability) | 51 Number of TEAEs |
| Cohort 4 - Active TMP-301 | Number of Treatment-Emergent Adverse Events (Safety and Tolerability) | 20 Number of TEAEs |
| Placebo | Number of Treatment-Emergent Adverse Events (Safety and Tolerability) | 6 Number of TEAEs |
Secondary
Apparent Total Plasma Clearance of TMP-301 After Extravascular Administration (CL/F)
Time frame: Day 14
Population: Subjects in Cohort 1 were withdrawn after Day 8, therefore Day 14 pharmacokinetic parameters were not estimated for this cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Apparent Total Plasma Clearance of TMP-301 After Extravascular Administration (CL/F) | 10.7 L/h | Standard Deviation 2.46 |
| Cohort 2 - Active TMP-301 | Apparent Total Plasma Clearance of TMP-301 After Extravascular Administration (CL/F) | 11.8 L/h | Standard Deviation 4.1 |
| Cohort 3 - Active TMP-301 | Apparent Total Plasma Clearance of TMP-301 After Extravascular Administration (CL/F) | 16.4 L/h | Standard Deviation 4.07 |
Secondary
Apparent Volume of Distribution of TMP-301 at Steady State (Vz/F)
Time frame: Day 14
Population: Subjects in Cohort 1 were withdrawn after Day 8, therefore Day 14 pharmacokinetic parameters were not estimated for this cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Apparent Volume of Distribution of TMP-301 at Steady State (Vz/F) | 2610 L | Standard Deviation 1930 |
| Cohort 2 - Active TMP-301 | Apparent Volume of Distribution of TMP-301 at Steady State (Vz/F) | 2390 L | Standard Deviation 1980 |
| Cohort 3 - Active TMP-301 | Apparent Volume of Distribution of TMP-301 at Steady State (Vz/F) | 5010 L | Standard Deviation 5010 |
Secondary
Area Under the Curve (Exposure) at Steady-state( AUC0_tau,ss), Over the Dosing Interval.
Time frame: Day 14
Population: Subjects in Cohort 1 were withdrawn Day 8, therefore Day 14 pharmacokinetic parameters were not estimated for this cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Area Under the Curve (Exposure) at Steady-state( AUC0_tau,ss), Over the Dosing Interval. | 4910 h*ng/mL | Standard Deviation 1210 |
| Cohort 2 - Active TMP-301 | Area Under the Curve (Exposure) at Steady-state( AUC0_tau,ss), Over the Dosing Interval. | 4630 h*ng/mL | Standard Deviation 1430 |
| Cohort 3 - Active TMP-301 | Area Under the Curve (Exposure) at Steady-state( AUC0_tau,ss), Over the Dosing Interval. | 1630 h*ng/mL | Standard Deviation 501 |
Secondary
Average Plasma Concentration of TMP-301 at 12 Hours After Last Dose (C12)
Time frame: Day 14
Population: Subjects in Cohort 1 were withdrawn after Day 8, therefore Day 14 pharmacokinetic parameters were not estimated for this cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Average Plasma Concentration of TMP-301 at 12 Hours After Last Dose (C12) | 204 ng/mL | Standard Deviation 50.3 |
| Cohort 2 - Active TMP-301 | Average Plasma Concentration of TMP-301 at 12 Hours After Last Dose (C12) | 193 ng/mL | Standard Deviation 59.8 |
| Cohort 3 - Active TMP-301 | Average Plasma Concentration of TMP-301 at 12 Hours After Last Dose (C12) | 67.7 ng/mL | Standard Deviation 21 |
Secondary
Maximum Plasma Concentration (Cmax) of TMP-301
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Maximum Plasma Concentration (Cmax) of TMP-301 | 149 ng/mL | Standard Deviation 86.5 |
| Cohort 2 - Active TMP-301 | Maximum Plasma Concentration (Cmax) of TMP-301 | 224 ng/mL | Standard Deviation 150 |
| Cohort 3 - Active TMP-301 | Maximum Plasma Concentration (Cmax) of TMP-301 | 220 ng/mL | Standard Deviation 93.9 |
| Cohort 4 - Active TMP-301 | Maximum Plasma Concentration (Cmax) of TMP-301 | 97.5 ng/mL | Standard Deviation 44.2 |
Secondary
Maximum Plasma Concentration (Cmax) of TMP-301 at Steady State
Time frame: Day 14
Population: Subjects in Cohort 1 were withdrawn after Day 8, therefore Day 14 pharmacokinetic parameters were not estimated for this cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Maximum Plasma Concentration (Cmax) of TMP-301 at Steady State | 464 ng/mL | Standard Deviation 114 |
| Cohort 2 - Active TMP-301 | Maximum Plasma Concentration (Cmax) of TMP-301 at Steady State | 517 ng/mL | Standard Deviation 125 |
| Cohort 3 - Active TMP-301 | Maximum Plasma Concentration (Cmax) of TMP-301 at Steady State | 220 ng/mL | Standard Deviation 70.8 |
Secondary
Minimum Drug Concentration (Cmin) of TMP-301 at Steady State
Time frame: Day 14
Population: Subjects in Cohort 1 were withdrawn Day 8, therefore Day 14 pharmacokinetic parameters were not estimated for this cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Minimum Drug Concentration (Cmin) of TMP-301 at Steady State | 125 ng/mL | Standard Deviation 37.3 |
| Cohort 2 - Active TMP-301 | Minimum Drug Concentration (Cmin) of TMP-301 at Steady State | 114 ng/mL | Standard Deviation 44.7 |
| Cohort 3 - Active TMP-301 | Minimum Drug Concentration (Cmin) of TMP-301 at Steady State | 30.1 ng/mL | Standard Deviation 21.4 |
Secondary
Plasma Concentration of TMP-301 at 12 Hours After First Dose (C12)
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Plasma Concentration of TMP-301 at 12 Hours After First Dose (C12) | 33.3 ng/mL | Standard Deviation 32.5 |
| Cohort 2 - Active TMP-301 | Plasma Concentration of TMP-301 at 12 Hours After First Dose (C12) | 34.4 ng/mL | Standard Deviation 25.4 |
| Cohort 3 - Active TMP-301 | Plasma Concentration of TMP-301 at 12 Hours After First Dose (C12) | 23.2 ng/mL | Standard Deviation 7.82 |
| Cohort 4 - Active TMP-301 | Plasma Concentration of TMP-301 at 12 Hours After First Dose (C12) | 9.92 ng/mL | Standard Deviation 4.43 |
Secondary
Plasma Concentration of TMP-301 at 24 Hours After First Dose (C24)
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Plasma Concentration of TMP-301 at 24 Hours After First Dose (C24) | 9.61 ng/mL | Standard Deviation 17.2 |
| Cohort 2 - Active TMP-301 | Plasma Concentration of TMP-301 at 24 Hours After First Dose (C24) | 9.23 ng/mL | Standard Deviation 6.91 |
| Cohort 3 - Active TMP-301 | Plasma Concentration of TMP-301 at 24 Hours After First Dose (C24) | 5.92 ng/mL | Standard Deviation 1.56 |
| Cohort 4 - Active TMP-301 | Plasma Concentration of TMP-301 at 24 Hours After First Dose (C24) | 2.32 ng/mL | Standard Deviation 2.54 |
Secondary
Plasma Concentration of TMP-301 at 24 Hours After Last Dose at Steady State (C24, ss)
Time frame: Day 14
Population: Subjects in Cohort 1 were withdrawn Day 8, therefore Day 14 pharmacokinetic parameters were not estimated for this cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Plasma Concentration of TMP-301 at 24 Hours After Last Dose at Steady State (C24, ss) | 121 ng/mL | Standard Deviation 27.9 |
| Cohort 2 - Active TMP-301 | Plasma Concentration of TMP-301 at 24 Hours After Last Dose at Steady State (C24, ss) | 120 ng/mL | Standard Deviation 45.7 |
| Cohort 3 - Active TMP-301 | Plasma Concentration of TMP-301 at 24 Hours After Last Dose at Steady State (C24, ss) | 31.2 ng/mL | Standard Deviation 20.6 |
Secondary
Terminal Half-life (T1/2) of TMP-301
Time frame: Day 14
Population: Subjects in Cohort 1 were withdrawn Day 8, therefore Day 14 pharmacokinetic parameters were not estimated for this cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Terminal Half-life (T1/2) of TMP-301 | 174.92 h | Standard Deviation 139.78 |
| Cohort 2 - Active TMP-301 | Terminal Half-life (T1/2) of TMP-301 | 125.86 h | Standard Deviation 66.25 |
| Cohort 3 - Active TMP-301 | Terminal Half-life (T1/2) of TMP-301 | 279.53 h | Standard Deviation 378.19 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of TMP-301
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Time to Maximum Plasma Concentration (Tmax) of TMP-301 | 2.80 h | Standard Deviation 0.84 |
| Cohort 2 - Active TMP-301 | Time to Maximum Plasma Concentration (Tmax) of TMP-301 | 2.67 h | Standard Deviation 1.04 |
| Cohort 3 - Active TMP-301 | Time to Maximum Plasma Concentration (Tmax) of TMP-301 | 3.01 h | Standard Deviation 1.11 |
| Cohort 4 - Active TMP-301 | Time to Maximum Plasma Concentration (Tmax) of TMP-301 | 3.17 h | Standard Deviation 0.76 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of TMP-301 at Steady State
Time frame: Day 14
Population: Subjects in Cohort 1 were withdrawn after Day 8, therefore Day 14 pharmacokinetic parameters were not estimated for this cohort.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | Time to Maximum Plasma Concentration (Tmax) of TMP-301 at Steady State | 1.86 h | Standard Deviation 0.77 |
| Cohort 2 - Active TMP-301 | Time to Maximum Plasma Concentration (Tmax) of TMP-301 at Steady State | 2.41 h | Standard Deviation 1.13 |
| Cohort 3 - Active TMP-301 | Time to Maximum Plasma Concentration (Tmax) of TMP-301 at Steady State | 2.41 h | Standard Deviation 1.15 |
Secondary
To Evaluate the Plasma Area Under the Curve (AUC) 0-12 Hours After First Dose of TMP-301
0-12 hours post-dose on Day 1, twice daily dosing
Time frame: Day 1
Population: Cohort 1 was twice daily dosing (BID). All other cohorts were once daily dosing (QD)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | To Evaluate the Plasma Area Under the Curve (AUC) 0-12 Hours After First Dose of TMP-301 | 888 h*ng/mL | Standard Deviation 607 |
Secondary
To Evaluate the Plasma Area Under the Curve (AUC) 0-24 Hours After First Dose of TMP-301
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 - Active TMP-301 | To Evaluate the Plasma Area Under the Curve (AUC) 0-24 Hours After First Dose of TMP-301 | 1310 h*ng/mL | Standard Deviation 848 |
| Cohort 2 - Active TMP-301 | To Evaluate the Plasma Area Under the Curve (AUC) 0-24 Hours After First Dose of TMP-301 | 1130 h*ng/mL | Standard Deviation 345 |
| Cohort 3 - Active TMP-301 | To Evaluate the Plasma Area Under the Curve (AUC) 0-24 Hours After First Dose of TMP-301 | 489 h*ng/mL | Standard Deviation 165 |