Healthy Adult Subjects
Conditions
Brief summary
This is a Phase 1, Randomized, Open-Label, Three-Treatment, Three-Period Crossover Study to Assess Bioequivalence and Safety of TTYP01 Tablets to Radicava® Injection, and Radicava ORS® in Healthy Adult Subjects Under Fasting Conditions.The objective is To characterize the bioequivalence、safety and tolerability of TTYP01 tablets and Radicava® injection or Radicava ORS®in healthy adult subjects under fasted conditions.In this study, 30 healthy adult subjects will receive TTYP01, or Radicava, orRadicava ORS in each period according to the randomization sequence.
Detailed description
This is a Phase 1, Randomized, Open-Label, Three-Treatment, Three-Period Crossover Study to Assess Bioequivalence and Safety of TTYP01 Tablets to Radicava® Injection, and Radicava ORS® in Healthy Adult Subjects Under Fasting Conditions. The Primary objective is To characterize the bioequivalence of TTYP01 tablets (Test) and Radicava® injection (Reference 1) or Radicava ORS® (Reference 2) in healthy adult subjects under fasted conditions. The secondary objective is To determine the safety and tolerability of TTYP01 tablets (Test), Radicava Injection (Reference 1), and Radicava ORS (Reference 2) in healthy adult subjects under fasted conditions. In this open-label, randomized, 3-formulation, 3-period, crossover study, 30 healthy adult subjects will receive 1 single oral dose of 90 mg TTYP01 (3 tablets of the test drugs, test formulation T), or 1 injection of 60 mg Radicava (reference drug R1, intravenous infusion of 60 mg administered over 60 minutes), or 1 single oral dose of 105 mg/5 mL Radicava ORS (reference drug R2) after an overnight fast in each period according to the randomization sequence. Subjects will be randomized to 1 of 6 parallel sequences (5 subjects per sequence), with a washout period of at least 96 hours between the periods. The approximate study period is 6 weeks, including screening and follow-up.
Interventions
DRUGTTYP01
1 single oral dose of 90 mg TTYP01 (3 tablets of the test drugs, test formulation T)
DRUGRadicava
1 injection of 60 mg Radicava (reference drug R1, intravenous infusion of 60 mg administered over 60 minutes)
DRUGRadicava ORS
1 single oral dose of 105 mg/5 mL Radicava ORS (reference drug R2)
Sponsors
Shanghai Auzone Biological Technology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must meet all inclusion criteria at screening (or as noted) to be eligible for study participation, as follows: 1. Informed consent signed and dated by the subject 2. Healthy male and female subjects of any ethnic and racial origin, aged 20 to 45 years, inclusive 3. Female subjects who: * Are postmenopausal (defined as a minimum of 12 consecutive months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone level \> 40 IU/L), or * Are surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), confirmed by medical documentations, or * Are of child-bearing potential must agree to use at least 1 highly effective method of contraception from at least 1 month prior to the initiation of the study through 3 months after the final dose, where highly effective methods of contraception include: * Intrauterine device * Intrauterine system * Contraceptive implant * Combined injectable contraceptives * Hormonal oral contraceptives when used in combination with male condoms with spermicide * If a female subject confirms that her male partner(s) has been verified to be clinically sterile (ie, documented infertility or surgical sterilization), this method is acceptable as the only means of contraception Note: The following are not acceptable methods of contraception: * Periodic sexual abstinence (eg, calendar, ovulation, symptothermal, and post-ovulation methods), declaration of sexual abstinence for the duration of the study, withdrawal, and lactational amenorrhea method * Spermicides alone * Hormonal oral contraceptives alone * Male condoms used in combination with female condoms or * Agrees to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. 4. Male subjects who are sexually active and whose partners are females of child-bearing potential, even if surgically sterilized (ie, status post vasectomy), who: * Avoid sperm donation during the entire study period and through 90 days after the last dose of study drugs, and * Agree to practice effective barrier contraception, or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject 5. Body mass index (BMI) of 19 to 30 kg/m2 (inclusive) (BMI = weight (kg)/(height \[m\])2) 6. Non-smokers (defined as having abstained from tobacco- or nicotine-containing products \[eg, cigarettes, chewing tobacco, snuff, nicotine patches, and electronic cigarettes\] in the 6 months prior to screening), stable light smokers, and ex-smokers will be included. Stable light and ex-smokers are defined as follows: "A light smoker is defined as someone smoking ≤5 cigarettes per day; an ex-smoker is someone who has completely stopped smoking for at least 3 months." 7. In good health, as determined by the investigator at screening and confirmed at check-in, with no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations 8. Subjects must be willing to understand and able to comply with all research procedures and restrictions, and are able to communicate effectively with researchers.
Exclusion criteria
Subjects will not be eligible for study participation if they meet any of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PK Parameters-Area under the plasma concentration-time curve (AUC0-inf) from time 0 extrapolated to infinity of unchanged edaravone after TTYP01, Radicava and Radicava ORS administration | up to 48 hours each postdose |
| PK Parameters- AUC from time 0 to the last measurable non-zero concentration（AUC0-t）of unchanged edaravone after TTYP01, Radicava and Radicava ORS administration | up to 48 hours each postdose |
| PK Parameters - Maximum observed concentration （Cmax） of unchanged edaravone after TTYP01, Radicava and Radicava ORS administration | up to 48 hours each postdose |
Secondary
| Measure | Time frame |
|---|---|
| PK Parameters-Area under the plasma concentration-time curve (AUC0-inf) from time 0 extrapolated to infinity of sulfate and glucuronide metabolites after TTYP01, Radicava and Radicava ORS administration | up to 48 hours each postdose |
| PK Parameters- AUC from time 0 to the last measurable non-zero concentration（AUC0-t）of sulfate and glucuronide metabolites after TTYP01, Radicava and Radicava ORS administration | up to 48 hours each postdose |
| PK Parameters - Maximum observed concentration （Cmax） of sulfate and glucuronide metabolites after TTYP01, Radicava and Radicava ORS administration | up to 48 hours each postdose |
| PK Parameters- Time to reach Cmax （Tmax）of unchanged edaravone, sulfate, and glucuronide metabolites after TTYP01, Radicava, and Radicava ORS administration | up to 48 hours each postdose |
| PK Parameters - Apparent terminal elimination half-life （T1/2el）of unchanged edaravone, sulfate, and glucuronide metabolites after TTYP01, Radicava, and Radicava ORS administration | up to 48 hours each postdose |
| PK Parameters - Apparent terminal elimination rate constant （Kel）of unchanged edaravone, sulfate and glucuronide metabolites after TTYP01, Radicava and Radicava ORS administration | up to 48 hours each postdose |
| PK Parameters -Apparent oral drug clearance (parent drug only) （CL/F）of unchanged edaravone after TTYP01and Radicava ORS administration | up to 48 hours each postdose |
| PK Parameters - Total clearance (CL) of unchanged edaravone after Radicava administration | up to 48 hours each postdose |
| PK Parameters - Mean residence time (MRT）of unchanged edaravone after Radicava administration | up to 48 hours each postdose |
| PK Parameters -Apparent volume of distribution Vz/F） of unchanged edaravone after TTYP01and Radicava ORS administration | up to 48 hours each postdose |
| PK Parameters - Volume of distribution during terminal phase (Vz) of unchanged edaravone after Radicava administration | up to 48 hours each postdose |
| Incidence and Number of Participants with Adverse events and adverse drug reactions | until the last follow-up visit, up to 6 weeks(including screening and follow-up) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRobert. Bass, MD
ICON plc
Outcome results
None listed