A Single-Dose, Randomized, Open-Label, 2-Way Crossover Study to Evaluate the Dose-Proportionality, Safety, and Tolerability of TNX-102 SL (Cyclobenzaprine HCl Sublingual Tablets) in Healthy Japanese and Chinese Subjects
A Single-Dose, Randomized, Open-Label, 2-Way Crossover Study to Evaluate the Dose-Proportionality, Safety, and Tolerability of TNX-102 SL (Cyclobenzaprine HCl Sublingual Tablets) in Healthy Japanese and Chinese Subjects
Primary Objectives: To characterize the pharmacokinetic (PK) profile and dose proportionality of cyclobenzaprine and norcyclobenzaprine following administration of 2.8 mg and 5.6 mg of TNX-102 SL (either one or two 2.8 mg tablets) under fasting conditions in Japanese and Chinese subjects. To retrospectively compare PK data from the Japanese and Chinese study subjects with existing data from a non-Asian Phase 1 study investigating the administration of 2.8 mg and 5.6 mg of TNX-102 SL under fasting conditions. Secondary Objective: To assess the safety and tolerability of TNX-102 SL (2.8 mg and 5.6 mg) in healthy Japanese and Chinese subjects.
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 Japanese or Chinese male or female. All subjects will complete a 3 generation genealogy chart. "Japanese" includes subjects with 4 grandparents born in Japan and of Japanese ethnicity; "Chinese" shall include subjects with 4 grandparents born in Mainland China and of Chinese ethnicity. 4. If female, meets one of the following criteria:
Is of childbearing potential who are sexually active with a male partner must be willing to use one of the following acceptable contraceptive methods throughout the study and for 30 days after the last study drug administration:
Is of non-childbearing potential, defined as surgically sterile (ie, has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation), or is in a postmenopausal state (ie, at least 1 year without menses and without an alternative medical condition prior to the Screening visit) 5. Aged at least 18 years but not older than 65 years 6. Body mass index (BMI) within 17.5 kg/m2 to 32.0 kg/m2 and a minimum body weight of 50.0 kg for males and 45.0 kg for females 7. Non- or ex-smoker (An ex-smoker is defined as someone who completely stopped using oral or other tobacco products (including betel nut) for at least 90 days prior to Screening) 8. 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
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. Presence of any oral piercings 4. Any existing oral, medical or dental condition that could potentially interfere with the sublingual administration of study drug, or interfere with the tolerability of study drug, or with the evaluation of administration site reactions 5. Any history of severe or unexplained oral or oropharyngeal swelling or edema 6. Any dental procedures (other than routine cleaning) and planned use of teeth whitening strips or prescription teeth-whitening products within 30 days prior to Screening and during the course of study participation 7. Clinically significant ECG abnormalities (eg, QTcF > 450 msec [males] or QTcF > 470 msec [females]) or vital sign abnormalities (systolic blood pressure lower than 90 or over 150 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or resting heart rate less than 45 or over 100 beats per minute) at Screening.
8. History of significant hypersensitivity to cyclobenzaprine or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs 9. Presence or history of significant gastrointestinal (including absorption or obstructive disorders), liver (including cholestasis) or kidney (including urinary retention) disease, or surgery that may affect drug bioavailability 10. History of significant cardiovascular (including significant arrhythmias, heart block, conduction disturbances, and congestive heart failure), pulmonary, hematologic, neurological, psychiatric (including history of previous suicidal ideation or behaviors), endocrine (including hyperthyroidism), immunologic or dermatologic disease 11. Showing suicidal tendency as per the C-SSRS (score >Type 1 ideation) administered at Screening (APPENDIX 8) 12. Clinically significant history of angle-closure glaucoma or increased intraocular pressure 13. Immunization with a Coronavirus Disease 2019 (COVID-19) vaccine in the 14 days prior to the first study drug administration 14. Scheduled immunization with a COVID-19 vaccine (first dose, second dose, or booster vaccination) during the study that, in the opinion of an investigator, could potentially interfere with subject participation, subject safety, study results, or any other reason 15. Major surgery with prolonged immobilization in the 4 weeks prior to the first study drug administration 16. History of significant alcohol abuse within 1 year prior to Screening or regular use of alcohol within 6 months prior to the Screening visit (regular use includes more than 14 units of alcohol per week [1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]) or positive urine alcohol test at Screening 17. History of significant drug abuse within 1 year prior to Screening or use of soft drugs (cannabis) within 3 months prior to the Screening visit or hard drugs (cocaine, phencyclidine, crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year prior to Screening 18. Any clinically significant illness in the 28 days prior to the first study drug administration 19. Use of medication other than topical products without significant systemic absorption and hormonal contraceptives: Electroconvulsive therapy or any antipsychotics (depot) within 6 months prior to Screening; antiparkinsonian, anticonvulsant, or antidepressant medications within 30 days prior to Screening; typical and atypical antipsychotics (non-depot), or lithium within 30 days prior to Screening; Depot injection or implant of any drug (other than hormonal contraceptives) within 3 months prior to the first dosing; Monoamine oxidase inhibitors within 30 days prior to the first dosing; Any drugs known to significantly induce or inhibit hepatic metabolism, including St. John's wort, within 30 days prior to the first dosing; Prescription medication within 14 days prior to the first dosing; Over-the-counter (OTC) products and natural health products (including herbal remedies, homeopathic and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports) within 7 days prior to the first dosing.
20. Hemoglobin < 12.8 g/dL (males) and < 11.5 g/dL (females) and hematocrit 36.0% (males) and 32.0% (females) at Screening 21. Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen, or hepatitis C virus tests 22. 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.
23. Inclusion in a previous group for this clinical study 24. Intake of cyclobenzaprine in the 28 days prior to the first study drug administration 25. Prior exposure to TNX-102 SL 26. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dose administration or 5 half-lives (whichever is longer), or concomitant participation in an investigational study 27. Donation of plasma within 7 days prior to dosing 28. Donation or loss of blood (excluding volume drawn at Screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL of blood within 56 days prior to the first dosing