A Phase 1, Open-Label, Parallel-Group, Single-Dose Study To Compare The Pharmakokinetics Of TNX-102 SL (Cyclobenzaprine Hydrochloride Sublingual Tablet) In Non-Elderly Versus Elderly Participants

A Phase 1, Open-Label, Parallel-Group, Single-Dose Study To Compare The Pharmakokinetics Of TNX-102 SL (Cyclobenzaprine Hydrochloride Sublingual Tablet) In Non-Elderly Versus Elderly Participants

TNX-102 SL has recently been approved by the United States (US) Food and Drug Administration (FDA) under the brand name TONMYA for the treatment of fibromyalgia. Fibromyalgia is a long-lasting condition that causes pain all over the body, along with feeling tired and not sleeping well. TNX-102 SL is not approved for any conditions in Canada.

The study looks at the safety and blood levels of a study drug called TNX-102 SL [cyclobenzaprine hydrochloride (HCl) sublingual (SL) tablets], taken under the tongue, and compares it in non-elderly and elderly male and female participants.

Inclusion Criteria:

• Male or female, with body mass index (BMI) >18.5 and <30.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.

• Group 1 non-elderly participants must be ≥18 and ≤45 years of age.

• Group 2 elderly participants must be ≥65 years of age.

• Healthy, or with stable chronic illness not contraindicated for cyclobenzaprine use for Group 2 elderly participants only (i.e., under stable treatment with the same medication for at least 3 months, with no change in dosage for at least 14 days before admission and no expected change throughout the study, and with medication that is not contraindicated and will not interfere in the PK or the assay of the administered cyclobenzaprine) as defined by:

  1. the absence of clinically significant illness and surgery within 4 weeks prior to admission.
  2. the absence of clinically significant history of neurological, endocrinological (including hyperthyroidism), cardiovascular (including significant arrhythmias, heart block, conduction disturbances, and congestive heart failure), respiratory, hematological, immunological, psychiatric (including history of previous suicidal ideation or behaviors), gastrointestinal (including absorption or obstructive disorders), renal (including urinary retention), hepatic (including cholestasis), and metabolic disease, with the exception of findings in Group 2 elderly participants that in the opinion of the Investigator are consistent with participant's normal aging and are not contraindicated for cyclobenzaprine use.
  3. the absence of clinically significant history of angle-closure glaucoma or increased intraocular pressure.

• Estimated glomerular filtration rate (eGFR; using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) ≥60 mL/min/1.73 m2 at screening and/or Day -1.

• Female participants of non-childbearing potential must be:

  1. post-menopausal (spontaneous amenorrhea for at least 12 months prior to admission) with confirmation by documented follicle-stimulating hormone (FSH) levels ≥40 IU/L; or
  2. surgically sterile (bilateral oophorectoy, bilateral salpingectomy, hysterectomy or tubal ligation) at least 3 months prior to admission.

Female participants of childbearing potential who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomized for at least 3 months prior to admission) must be willing to use one of the following acceptable contraceptive methods throughout the study and for 30 days after dosing: a. simultaneous use of hormonal contraceptive (e.g., oral, patch, depot injection, implant, vaginal ring, intrauterine device) or non-hormonal intrauterine device used for at least 4 weeks prior to admission (must agree to use the same contraceptive throughout the study) and condom for the male partner; b. simultaneous use of diaphragm or cervical cap with spermicide and condom for the male partner, started at least 21 days prior to admission.

• Willing to take off dentures or mouth piercing or any other removable oral appliance at the time of dosing, if applicable.
• Able to understand the study procedures and provide signed informed consent to participate in the study.

Exclusion Criteria:

• Any clinically significant abnormal finding at physical examination at screening and/or Day -1.

• C-SSRS score above Type 1 ideation.

• Clinically significant abnormal laboratory test results at screening and/or Day -1; or positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen/antibody at screening.

• Use of tobacco or nicotine products within 3 months prior to screening.

• Positive pregnancy test at screening and/or Day -1; or lactating female participant.

• Positive urine drug screen, urine cotinine test, or alcohol breath test at screening and/or Day -1.

• History or known allergic reactions to cyclobenzaprine or other related drugs, or to any excipient in the formulation.

• History of anaphylaxis reaction, a documented hypersensitivity reaction, or a clinically significant reaction to any drug.

• Clinically significant ECG abnormalities or vital signs abnormalities for Group 1 non-elderly participants (systolic BP lower than 90 or over 140 mmHg, diastolic BP lower than 50 or over 90 mmHg, or HR less than 50 or over 100 bpm) or vital signs abnormalities for Group 2 elderly participants (systolic BP lower than 90 or over 150 mmHg, diastolic BP lower than 50 or over 95 mmHg, or HR less than 50 or over 100 bpm) at screening and/or Day -1.

• History of drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening.

• History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units for women or 15 units for men of alcohol per week (1 unit = 340 mL of beer 5%, 140 mL of wine 12%, or 45 mL of distilled alcohol 40%).

• History or current evidence of oral neoplasm or leukoplakia, history of salivary infections or stones, or presence of any other abnormality involving the oral cavity that, in the opinion of the Investigator, might interfere with the tolerability of study drug or the evaluation of administration site reactions.

• Use of medications for the timeframes specified below:

  1. electroconvulsive therapy (ECT) 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; tramadol, meperidine, or verapamil within 30 days prior to screening;
  2. depot injection or implant (other than hormonal contraceptives) within 3 months prior to admission;
  3. monoamine oxidase inhibitors (MAOIs) within 30 days prior to admission;
  4. any drug known to induce or inhibit hepatic drug metabolism, including St. John's wort, within 30 days prior to admission;
  5. prescription medications within 14 days prior to admission;
  6. any vaccine, including COVID-19 vaccine, within 14 days prior to admission; g. over-the-counter (OTC) medications 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 admission. EXCEPTIONS* include: For Group 2 elderly participants only: stable medications (as defined in Inclusion Criteria no.3); and OTC or natural health products used as part of routine care that have been approved by the Investigator in agreement with Sponsor. For both Group 1 non-elderly participants and Group 2 elderly participants: medications required for the medical management of an AE, occasional use of acetaminophen (up to 2 g daily) or nonsteroidal anti-inflammatory drugs (NSAIDs, up to 1.2 g daily); hormonal contraceptives; and medications exempted by the Investigator on a case-by-case basis because they are judged unlikely to affect the PK profile of the study drug or participant safety (e.g., topical drug products without significant systemic absorption). *NOTE: Any exceptions allowed must be approved by the Investigator in agreement with Sponsor, unless deemed by the Investigator as required for the immediate safety of the participant.

• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to admission, administration of a biological product in the context of a clinical research study within 90 days prior to admission, or concomitant participation in an investigational study involving no drug or device administration.

• Donation of plasma within 7 days prior to admission or donation or loss of 500 mL or more of whole blood within 8 weeks prior to admission.

• Presence of orthodontic braces or orthodontic retention wires, or any physical findings in the mouth or tongue that would be likely to interfere with successful completion of the dosing procedure.

• Any minor dental procedures (other than routine cleaning) including teeth whitening within 2 weeks prior to admission and/or any major dental procedures within 3 months prior to admission. Participants will also refrain from undergoing any elective minor or major dental procedures throughout the study.

• Inability to be venipunctured and/or tolerate catheter venous access.

• Previous exposure to cyclobenzaprine within 30 days prior to screening.

• Any reason which, in the opinion of the Investigator, would prevent the participant from participating in the study.