Healthy Adult Participants
Conditions
Keywords
Ketamir-2, Ketamir hemipamoate, healthy participants, Phase 1, Single ascending dose, Multiple Ascending dose, Safety, Tolerability, neuropathic, neuropathic pain
Brief summary
This is a prospective, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and pharmacokinetics of oral Ketamir-2 in healthy adult participants. The study includes single ascending dose cohorts and multiple ascending dose cohorts.
Interventions
DRUGKetamir-2
Ketamir-2, also referred to as Ketamir hemipamoate, was administered orally as capsules containing 50 mg or 300 mg. Participants randomized to active treatment received Ketamir-2 according to assigned dose cohort. Cohorts 1 through 4 received a single dose on Day 1. Cohorts 5 through 7 received once-daily dosing from Day 1 through Day 5. Capsules were swallowed together with a glass of water after an overnight fast.
DRUGPlacebo
Placebo capsules were identical in appearance to active capsules and were administered orally according to the same number of capsules and dosing schedule as the corresponding Ketamir-2 dose cohort.
Sponsors
MIRA Pharmaceuticals
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants were enrolled sequentially into 7 ascending-dose cohorts. Cohorts 1 through 4 comprised the single ascending dose portion of the study, and Cohorts 5 through 7 comprised the multiple ascending dose portion. Within each cohort, participants were randomized in a 3:1 ratio to receive Ketamir-2 or matching placebo, respectively. Sentinel dosing was used in each cohort, with one participant receiving active treatment and one participant receiving placebo before dosing the remaining participants in the cohort. Dose escalation occurred after review of safety and tolerability data of the prior cohort by the Safety Steering Committee. The transition from Cohort 4 to Cohort 5 was reviewed and confirmed by an independent Data Safety Monitoring Committee, which also reviewed pharmacokinetic data from Cohorts 1 through 4.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male and female participants, ages 18-65. 2. Understands the study procedures described in the Informed Consent Form, be willing and able to comply with the protocol, and provides written consent. 3. Not pregnant or lactating and willing to comply with the contraceptive requirements from enrollment to 3 months post last dose. 4. In good health with no history of clinically significant medical conditions or suicide liability that would interfere with participant safety, as defined by medical history, physical examination and routine laboratory tests, ECG and determined by the Investigator at an admission evaluation. 5. Participants will have a documented medical history either prior to entering the study and/or following medical history review with the study physician at screening.
Exclusion criteria
1. History or evidence of any clinically significant or currently active cardiovascular, (including thromboembolic events), respiratory, dermatological, gastrointestinal, endocrine, hematological, hepatic, immunological, rheumatological, metabolic, urological, renal, neurological, psychiatric illness. 2. History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the principal investigator (PI). 3. History or presence of alcohol addiction, or excessive use of alcohol, or use of drugs of abuse. 4. Psychiatric illness including participants with a history of depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis. 5. Participants who are currently smoking or former regular cigarette smokers. 6. Body Mass Index (BMI) ≤18 Kg/m2 and ≥28 Kg/m2. 7. Venous access is deemed inadequate for the phlebotomy and cannulation demands of the study. 8. At the discretion of the PI, any clinically significant abnormal finding on screening biochemistry, hematology, serology microbiology blood tests or urinalysis or positive HIV, active/chronic hepatitis B or C test. 9. Twelve-lead ECG recording with clinically relevant abnormalities as judged by the study physician/PI. 10. Receipt of blood or blood products, or loss (including blood donations) of 550 mL or more of blood during the 3 months prior to screening. 11. Use of any medication or product (prescription or over the counter), including therapeutics for central nervous system activity (such as Ritalin, and its derivatives, antidepressants, hypnotics, anti-psychotics, or similar) within 14 days or 5 half-lives (whatever is longer) prior to screening until completion of the study. 12. Receipt of any investigational drug within 3 months prior to screening or receipt of three or more investigational drugs within the previous 12 months prior to screening. 13. Over the counter medications (e.g., paracetamol or ibuprofen) where the dose taken over the preceding 14 days prior to the planned date of drug administration had exceeded the maximum permissible 24-hour dose. 14. Participants who have received any systemic chemotherapy agent, immunoglobulins, or other cytotoxic or immunosuppressive drugs at any time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Bowdle Visual Analog Scale (VAS) Score | From baseline through end of study visit | The Bowdle VAS is a tool used to measure the psychedelic effects of substances. It consists of 13 items (each scored on 0-100 mm) that assess both internal perception and external perception. Higher scores indicate greater subjective effects. |
| Number of Participants With Clinically Significant Vital Sign Abnormalities | From baseline through end of study visit | Vital sign assessments include blood pressure, heart rate, respiratory rate, and oral temperature. Clinically significant vital sign abnormality is determined by the investigator. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities on a 12-Lead ECG | From baseline through end of study visit | Safety ECG will be assessed using 12-lead ECG recordings. Clinically significant abnormality is determined by the investigator. |
| Number of Participants With Clinically Significant Physical Examination Findings | From baseline through end of study visit | A focused physical examination will be performed prior to dosing on Day 1 and upon discharge on Day 2. For cohorts 5-7, a focused physical examination will be performed prior to dosing on Day 1, on Day 3, and Day 6. Examination of the cardiovascular system is mandatory, while the other body systems will be examined at the discretion of the Principal Investigator. |
| Number of Participants With Ketamine-Related Side Effects as Assessed by the Ketamine Side Effect Tool (KSET) | From baseline through end of study visit | The Ketamine Side Effect Tool will be used to assess ketamine-related side effects. |
| Number of Participants with Incidence of adverse events | From first dose through dosing period until 7 days post last dose | — |
| Number of Participants With Clinically Significant Clinical Laboratory Abnormalities | From baseline through end of study visit | Clinical laboratory assessments include urinalysis and blood tests. Clinically significant laboratory abnormality is determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) of Ketamir-2 | Single Ascending Dose cohorts: Day 1 through Day 2; Multiple Ascending Dose cohorts: Day 1 through Day 6 | — |
| Area Under the Plasma Concentration Versus Time Curve (AUC) | Single Ascending Dose cohorts: Day 1 through Day 2; Multiple Ascending Dose cohorts: Day 1 through Day 6 | — |
| Time to Reach Maximum Plasma Concentration (Tmax) | Single Ascending Dose cohorts: Day 1 through Day 2; Multiple Ascending Dose cohorts: Day 1 through Day 6 | — |
| Percent of Dose Recovered in Urine Over each Collection Period | Single Ascending Dose cohorts: Day 1 through Day 2; Multiple Ascending Dose cohorts: Day 1 through Day 6 | Urine samples will be obtained prior to first dosing, every 3 hours up to 12 hours post-dose, and 12-24 hours post-dose. |
Countries
Israel
Outcome results
None listed