Clinical TrialPTSDKetaminePlaceboNot yet recruiting
A Phase 1, Single Centre, Randomised, Double Blind, Placebo Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of NeuroDirect Ketamine in Healthy Adult Volunteers
This Phase I trial (n=24) will investigate the safety, tolerability, and pharmacokinetics of NeuroDirect Ketamine in healthy adult volunteers.
Target Enrollment
24 participants
Study Type
Phase I/II interventional
Design
Randomized, double Blind
Registry
Detailed Description
Randomised, double-blind, placebo-controlled single-ascending dose study in healthy adults to evaluate safety, tolerability and pharmacokinetics of topically administered NeuroDirect Ketamine and to determine a recommended phase 2 dose.
Three cohorts (25, 50, 100 mg) with 8 participants each (6 active, 2 placebo). PK sampling includes plasma at pre-dose, 0.5,1,2,4,6,8,12 h and 24,48,72,96 h; urine at pre-dose, 1,24,48,72,96 h; one CSF sample at 0.5 h post-dose.
Study Protocol
Preparation
sessions
Dosing
1 sessions
Integration
sessions
Study Arms & Interventions
NeuroDirect Ketamine
experimentalTopical single-ascending dose cohorts (25, 50, 100 mg); 6 active : 2 placebo per cohort; progression by SRC based on safety.
Interventions
- Ketamine25 - 100 mgvia Topical• single dose• 1 doses total
Cohorts: 25 mg (Cohort 1), 50 mg (Cohort 2), 100 mg (Cohort 3); 1 ml applied to back of neck at hairline between C3–C4. SRC-guided escalation.
Placebo
inactiveGlycerine-based cream placebo, applied topically in identical manner.
Interventions
- Placebovia Topical• single dose• 1 doses total
Glycerine-based cream placebo, 1 ml applied to back of neck between C3–C4.
Participants
Ages
18 – 60
Sexes
Male & Female
BMI
18 - 32
Psychosis History
-
Inclusion Criteria
- To be eligible for this study, participants must meet all of the following inclusion criteria:
- 1. Healthy male or female volunteers aged between 18 to 60 years (inclusive) at the time of informed consent.
- 2. Capable of understanding the purposes and risks of the study and able to provide written informed consent before any study-specific screening procedures are performed.
- 3. Willing and able to adhere to all protocol requirements, including willingness to comply with scheduled visits.
- 4. Body weight = 50 kg, and a body mass index (BMI; Quetelet index) in the range 18.0 to 32.0, inclusive.
- 5. Subject is free from clinically significant (in the opinion of the Investigator) illness or disease as determined by their medical and surgical history, physical examination, 12-lead ECG, vital signs and clinical laboratory determinations.
- 6. Adequate venous access in both arms for collection of a number of blood samples.
- 7. Negative urine drug/alcohol breath testing at Screening and prior to randomisation. Note: Screening urine drug test/alcohol breath testing may be repeated once if deemed appropriate by the Investigator.
- 8. Must have a negative COVID-19 PCR test on Day -1
- 9. If a subject is undergoing vaccination against Covid 19 virus, must wait 14 days after vaccination before first dose of investigational drug.
- 10. Female participants must meet 1 of the following criteria:
- a) Not of childbearing potential, defined as surgically sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy - verbal confirmation through medical history review acceptable) or postmenopausal (i.e., no menses for at least 12 months). Postmenopausal status is to be confirmed by testing follicle-stimulating hormone [FSH] levels or local practice.
- b) Of childbearing potential and agrees to take effective contraceptive measures throughout the study period (i.e., highly effective birth control method such as hormonal contraception or intrauterine device [IUD], or abstinence, when in line with preferred or usual lifestyle), from study entry (i.e., Screening) until at least 3 months after the last dose of study drug. Contraception requirements do not apply for participants in an exclusively same-sex relationship.
- c) Of childbearing potential and in an exclusive relationship with a partner who has had a bilateral vasectomy at least 6 months prior to study entry.
- 11. Male participant: has undergone bilateral vasectomy (at least 6 months prior to study entry) and has documented evidence of azoospermia at least 90 days post procedure. or agrees to use effective contraceptive effective contraceptive measures (i.e. condoms for all types of sexual intercourse; plus use of a highly effective birth control method by their female partner, if they are of childbearing potential [see Inclusion Criteria 10]; or abstinence, when in line with preferred or usual lifestyle) and not donate sperm throughout the study period from study entry (i.e., Screening) until at least 3 months after the last dose of study drug.
Exclusion Criteria
- A participant who meets any of the following exclusion criteria must be excluded from the study:
- 1. History of severe allergic or anaphylactic reactions, known intolerance, allergy or hypersensitivity reactions to Ketamine.
- 2. History of coronary disease, peripheral vascular disease, cerebrovascular accident, transient ischaemic attack, uncontrolled hypertension or signs/symptoms of ischaemic heart disease.
- 3. Mean baseline blood pressure above 130/80 mm Hg.
- 4. History of neurologic conditions such as seizures or convulsive disorders (including epilepsy), severe head injury or increased intracranial pressure. A history of childhood febrile seizures is allowed.
- 5. Presence of current psychiatric condition or psychiatric condition requiring pharmacological management within the last 6 months.
- 6. Positive results of a screen for PTSD through a validated PTSD rating scale questionnaire
- 7. A calculated creatinine clearance of < 85 mL/minute at Screening or pre randomisation according to the equation using Cockcroft and Gault.
- 8. Liver function tests showing values for ALT or AST > 1.5 times ULN at Screening.
- 9. Evidence or history of clinically significant (in the opinion of the Investigator) other cardiovascular, pulmonary, neurologic or renal disorders or hepatic, gastrointestinal, oral (difficulty swallowing / taking oral medication), haematological, endocrine, or psychiatric impairment/disorders.
- 10. Have undergone surgery requiring or have received (for any reason) anaesthetic within 30 days of Day 1, or planned surgery during the study.
- 11. Use of CNS depressants including opioids, sedative, anxiolytics, hypnotics, neuroleptics, phenothiazines, tranquilisers, skeletal muscle relaxants, sedating antihistamines or cimetidine within 30 days of Day 1. 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. Thirty-day washout from these medications is required.
- 12. Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 1 month or 5 half-lives of the specific drug/biologic (whichever is longer) prior to dosing.
- 13. Donation or loss of more than 500 mL of blood within 30 days of Day 1 and/or plans to donate blood during the study.
- 14. Use of any prescription medication within 14 days of Day 1 and for duration of study, unless approved by both the Investigator and the Medical Monitor (in writing). If necessary, paracetamol (acetaminophen) or ondansetron (or other 5-HT3 receptor antagonist) may be administered with the approval of the Investigator.
- 15. Use of any over the counter product, herbal product, diet aid, or hormone supplement, with a particular regard to hemp or products containing cannabidiol, within 14 days of Day 1 and for duration of study, unless approved by both the Investigator and Medical Monitor (in writing).
- 16. Evidence or history of substance or alcohol abuse (drink more than 4 standard units of alcohol per day or >14 standard units per week), including positive results for the urine drugs of abuse test or a positive alcohol breath test at Screening or at Check-In (Day -1).
- 17. Unwilling or unable to abstain from recreational drug/substance use, from 48 hours before check-in until final study visit.
- 18. Consumption of grapefruit, grapefruit juice or any products containing CYP3A4 inhibitors and inducers within 14 days of Day 1 and through to completion of the study.
- 19. Subjects who are not willing or are unable to refrain from nicotine products or smoking 24 hours before check-in until completion of the confinement period.
- 20. History of significant alcohol abuse within 6 months of screening or any indication of regular use of more than 14 units of alcohol per week for female subjects and 21 units of alcohol per week for male subjects (1 unit is 360 mL of beer or 45 mL of alcohol 40%, or 150 mL of wine), and unwilling to refrain from consumption of alcohol from 24 hours before check-in until completion of the confinement period.
- 21. The use of more than 10 cigarettes, nicotine products per day or use of vaping device or e-cigarettes ten times per day within the past 30 days.
- 22. Unwilling or unable to abstain from caffeinated or other xanthine-containing products from check-in until completion of the confinement period.
- 23. Positive screening test for Human Immunodeficiency Virus (HIV) antibodies, Hepatitis B surface antigen or Hepatitis C antibody.
- 24. Malignancy within 5 years of screening visit (excluding non-melanoma skin cancer that has been resected).
- 25. Female subject that is pregnant or lactating.
- 26. Subject who is considered unsuitable for participating in the study in the opinion of the investigator.