None listed
Conditions
Brief summary
This study is testing a new oral form of a medicine called esketamine (Chir-110) in healthy adult volunteers. Esketamine is a medicine that acts on the brain and is already used in some settings to treat depression. This study is investigating a new capsule form taken by mouth to better understand how the body absorbs and processes the drug, and whether it is safe and well tolerated. Participants will receive a single dose of either Chir-110 or a placebo (a capsule with no active medicine). The study will test different dose levels in small groups, starting with a low dose and increasing step-by-step if it is safe to do so. Participants will be closely monitored at the clinical research unit on the day of dosing and will attend follow-up visits over about one week. During the study, researchers will collect blood and urine samples and check participants’ health, including heart activity, vital signs, and any side effects. The main aim of the study is to assess the safety and tolerability of Chir-110, as well as how the drug is processed in the body and its effects on the brain. It is expected that Chir-110 will be safe and well tolerated at the dose levels studied, and that the results will help determine appropriate doses for future clinical studies.
Interventions
Chir-110 is an oral capsule formulation of esketamine hydrochloride. Each capsule contains 50 mg esketamine hydrochloride. Participants randomized to active treatment will receive a single oral dose of Chir-110 on Day 1 under direct medical supervision at the study site. Planned single ascending dose cohorts are 50 mg (1 capsule), 100 mg (2 capsules), and subsequent cohorts up to a planned maximum of 300 mg, with later dose levels determined by review of emerging safety, pharmacokinetic and phar
Chir-110 is an oral capsule formulation of esketamine hydrochloride. Each capsule contains 50 mg esketamine hydrochloride. Participants randomized to active treatment will receive a single oral dose of Chir-110 on Day 1 under direct medical supervision at the study site. Planned single ascending dose cohorts are 50 mg (1 capsule), 100 mg (2 capsules), and subsequent cohorts up to a planned maximum of 300 mg, with later dose levels determined by review of emerging safety, pharmacokinetic and pharmacodynamic data by the Safety Review Committee. Dose escalation may be modified, repeated, reduced, or increased above 300 mg if prespecified pharmacokinetic safety thresholds are not exceeded. The intervention is delivered at a single clinical study site to healthy adult participants. Dosing occurs after eligibility reconfirmation and randomization. Participants fast for at least 10 hours before dosing and continue fasting until at least 4 hours after dosing. Fluids are restricted from 1 hour before until 1 hour after dosing, except for 240 mL water given with study drug. Participants remain at the site for a 12-hour post-dose confinement/observation period on Day 1. Trained clinical staff are present throughout confinement, and the investigator or designee is on site for dosing and for at least 6 hours post-dose. The intervention schedule includes screening from Day -28 to Day -2, optional eligibility reconfirmation on Day -1, dosing on Day 1, and follow-up visits on Days 2, 4 and 7, with an additional Day 3 pharmacokinetic sampling visit at either the study site or a designated local pathology centre. The protocol includes intensive post-dose assessments to characterise safety, tolerability, pharmacokinetics and pharmacodynamics, including blood and urine pharmacokinetic sampling and pharmacodynamic questionnaires (DEQ and CADSS). Each cohort includes 2 sentinel participants dosed first (1 active, 1 placebo), followed at least 48 hours later by the remaining participants if safety is acceptable. The Safety Review Committee reviews blinded safety, tolerability, pharmacokinetic and pharmacodynamic data after each cohort and may escalate, de-escalate, repeat, or stop dose progression according to prespecified rules. Intervention adherence/fidelity is ensured by on-site administration under supervision, with dosing time recorded as the time all capsule(s) are swallowed. Fidelity is further supported through controlled fasting/fluid requirements, direct clinical observation during confinement, protocol-specified assessment windows, and drug accountability procedures managed by designated site/pharmacy staff. Safety monitoring includes adverse event review, physical examination, vital signs, ECGs, clinical laboratory testing, and suicidality assessment (C-SSRS).
Sponsors
Chiral Biotech Pharma
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female, non-smoker (no use of tobacco or nicotine products within 6 months prior to first dose) 2. Aged more than or equal to 18 and less than or equal to 55 years 3. BMI more than 18.0 and less than 32.0 kg/m2 and body weight more than or equal to 50.0 kg. 4. Participant is judged by the Investigator to be in generally good health on the basis of medical history, physical examination, or clinical laboratory results during the screening. 5. Pulse between 45 and 100 beats per minute (bpm) at screening (inclusive) 6. Seated systolic BP between 90 and 160 mmHg, diastolic BP between 50 and 95 mmHg inclusive, at screening. For the purpose of qualifying any given participant for study participation, out-of-range vital signs may be repeated once. 7. No known history or family history of schizophrenia or other psychotic illness; history or presence of severe personality disorder or other significant psychiatric history or mental illness (in the opinion the Investigator). 8. Must have hepatic and renal clinical laboratory test results (ALT, AST, total bilirubin and eGFR) within a laboratory defined normal range. 9. Must not be pregnant, breastfeeding (non-lactating), or planning pregnancy. 10. Female participants must have negative serum hCG pregnancy test at screening and negative urine test at check-in. 11. Females of childbearing potential who are sexually active with a non-sterile male partner (sterile male partners are defined as men vasectomised at least 6 months prior to the first study drug administration) must be willing to use one of the following acceptable contraceptive methods throughout the study and for at least 3 months after the last study drug administration: a. Simultaneous use of intrauterine contraceptive device without hormone release system placed at least 4 weeks prior to the first study drug administration; or intrauterine contraceptive device with hormone release system placed at least 12 weeks prior to first study drug administration; or oral hormonal contraceptives (minimum 12 week use without issue), and a condom for the male partner. 12. Females of non-childbearing potential must be: a. Post-menopausal (absence of menses for at least 12 months prior to the first study drug administration) with confirmation of the post menopausal status by documented FSH level more than or equal to 40 mIU/mL; or b. Surgically sterile (complete hysterectomy or bilateral oophorectomy at least 3 months prior to the first study drug administration). 13. Female participants must be willing not to donate ova for 30 days after the last dose 14. All male participants (including men who have had a vasectomy) must agree to use a condom from the first dose and for 90 days after the last dose. 15. Male participants who are not vasectomised for at least 3 months prior to dosing and who are sexually active with a female partner of childbearing potential must be willing to use one of the following acceptable contraceptive methods from the first dose and for 90 days after the last dose: a. Simultaneous use of condom and established use of oral, injected or implanted hormonal contraceptive or placement of intrauterine device (IUD) or intrauterine system (IUS) for the female partner; 16. Male participants must be willing not to donate sperm for 90 days after the last dose. 17. Willing and able to adhere to all study requirements, including willingness to remain in the study unit for the requested duration of the confinement period on Day 1 1. 18. Able to understand the study procedures and provide signed and dated participant informed consent form (PICF) to participate in the study prior to screening.
Exclusion criteria
1. History of any clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, or cardiovascular disease or other condition which would jeopardize safety or impact validity of results (in the opinion the Investigator). 2. History of severe allergic or anaphylactic reactions, known intolerance, allergy or hypersensitivity reactions to Esketamine 3. History of coronary disease, peripheral vascular disease, cerebrovascular accident, transient ischemic attack, uncontrolled hypertension or signs/symptoms of ischemic heart disease. 4. Participant has any documented history of, or currently active, seizure disorder or history of clinically significant head injury or history of intracerebral hemorrhage 5. Has undergone surgery requiring or has received (for any reason) anesthetic within 30 days of Day 1, or has planned surgery during the study 6. Participant has an active malignancy of any type or has been diagnosed with cancer within 5 years prior to screening (excluding squamous or basal cell carcinoma of the skin). 7. Any laboratory test results deemed clinically significant by the Investigator or positive test serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody at screening. 8. Clinically significant ECG abnormalities (Fridericia’s corrected QT interval [QTcF] more than 450 ms for males and more than more than 470 ms for females), PR more than 210 ms, QRS interval more than 120 ms at screening. 9. Clinically significant bradycardia or tachycardia defined as resting heart rate (HR) less than 40 bpm or more than 100 bpm, respectively. 10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels more than 1.50 times the upper limit of normal at screening. 11. Positive urine drug screen, urine cotinine and urine alcohol test and at screening or check-in. Testing for any out-of-range laboratory tests (ex.criteria # 8-11) values may be repeated once at the discretion of the Investigator. 12. Known allergic reactions to any excipient in the formulations. 13. History of significant drug abuse such as cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and amphetamine derivatives within 1 year prior to screening. 14. Use of marijuana (directly or indirectly) within 90 days prior to drug administration and during the course of the study. 15. History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit that exceeds 14 units of alcohol per week (1 unit equals 150 mL of wine, 375 mL of mid strength beer, or 30 mL of distilled alcohol 40%). 16. Use of medications for the timeframes specified below, with the exception of 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): a. Prescription medications (except for non-hormonal contraceptives) within 14 days prior to the first dose until end of the study. b. Monoamine oxidase inhibitors (MAOIs) within 28 days prior to dosing. c. Over-the-counter products and natural health products (including herbal remedies such as St. John’s wort, homeopathic and traditional medicines), and antacid preparations within 14 days prior to the first dose up to end of study. Vitamins used as nutritional supplements in non-therapeutic doses (judged by the qualified Investigator or designee) may be accepted, but they must be stopped at least 48 hours before dosing and during the study. d. Any drugs known to induce or inhibit hepatic and renal drug metabolism within 30 days prior to the first dose and during the study. e. Any drugs that have a significant impact on the CNS including benzodiazepines (e.g., Diazepam, Alprazolam, Lorazepam), Antipsychotic medications (e.g., Haloperidol, Risperidone, Quetiapine), Antidepressants (e.g., Sertraline, Fluoxetine, Escitalopram), Antiepileptic drugs (e.g., Phenytoin, Carbamazepine, Valproate) or Sedative-hypnotics (e.g., Zolpidem, Zopiclone, Eszopiclone) within 30 days prior to the first dose and during the study. f. Use of macrolide antibiotics (e.g., Erythromycin), azole antifungal agents (e.g., Ketoconazole) or protease inhibitors (e.g., Ritonavir) within 30 days of Day 1. 17. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dose, administration of a biological product in the context of a clinical research study within 90 days prior to the first dose, or concomitant participation in an investigational study involving no drug or device administration. 18. Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 56 days prior to Day -1. 19. Any reason which, in the opinion of the Investigator, would compromise the participant from participating in the study
Outcome results
None listed