None listed
Conditions
Brief summary
This Phase 1 study will evaluate the safety, tolerability and pharmacokinetics of single and multiple ascending oral doses of OV4071 in healthy participants. It is hypothesised that OV4071 will be safe and well tolerated within predefined exposure limits supporting further clinical development.
Interventions
The study will be a Phase 1, single- center, randomized, double-blind, parallel, placebo controlled, inpatient study of the safety and tolerability of single and multiple ascending doses(s) of oral OV4071 in healthy male and female participants. The study consists of two parts: Part A approximately 7 single ascending dose (SAD) administered as oral capsules at a starting dose of 10 mg. Subsequent dose levels will follow a predefined escalation scheme based on emerging safety, tolerability and ph
The study will be a Phase 1, single- center, randomized, double-blind, parallel, placebo controlled, inpatient study of the safety and tolerability of single and multiple ascending doses(s) of oral OV4071 in healthy male and female participants. The study consists of two parts: Part A approximately 7 single ascending dose (SAD) administered as oral capsules at a starting dose of 10 mg. Subsequent dose levels will follow a predefined escalation scheme based on emerging safety, tolerability and pharmacokinetic data reviewed by the Data Review Committee (DRC). Dose escalation will not exceed a three-fold increase relative to the previous dose level with a minimum dose level of 10 mg and maximum dose level up to 800 mg. The minimum and maximum dose ranges are within the predefined non-clinical exposure limit of Cmax of 1655 ng/mL . Part C is a Multi Dose Ascending (MAD) with up to 4 ascending doses administered as oral capsules, daily for 7 days. Dose escalation will not exceed a three-fold increase relative to the previous dose level with a minimum dose level of 10 mg and maximum dose level up to 800 mg. The minimum and maximum dose ranges are within the predefined non-clinical exposure limit of Cmax of 1655 ng/mL . MAD cohorts can be conducted in parallel but dosing in a MAD cohort will only be initiated after the dose is cleared in a SAD cohort. For both SAD and MAD all doses are administered in-clinic under direct supervision of the trained study staff members and mouth checks are performed after each administration to confirm capsule ingestion. This information is documented in the study source documents. The study sponsor, the study principal investigator (PI), medical monitor, and a pharmacokineticist will review data summaries from each cohort and recommend whether to proceed with dose escalation, or MAD cohort dosing. The study will assess the safety profile of oral OV4071 on ECG parameters, vital signs, physical and neurological examinations, hematology and chemistry laboratory results and adverse events (AEs). In addition, neurophysiologic pharmacodynamic (PD) variables in the study are qualitative electrocardiogram (ECG), particularly the timing and extent of ECG changes in relation to the doses administered. In both SAD and MAD a sentinel group of 2 participants (1 active: 1 placebo) will be randomised and dosed ahead of the rest of the cohort. These 2 participants will be monitored for 2 days until the end of the in-patient portion of Part A (Day 3) and for 8 days for the in-patient portion of Part C (Day 9) before their available data will be reviewed by the Principal Investigator (PI). The remaining 6 participants will be dosed once the PI has concluded that it is safe to proceed with the rest of the cohort. Monitoring visits by the CRO to the study site will be made periodically during the study to ensure all aspects of the protocol are followed.
Sponsors
Ovid Therapeutics Australia Pty Ltd
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. Participant must give written informed consent prior to participation in the study. 2. Participant agrees not to post any of the participant's personal or medical data or information related to the study on any website, message board(s), online groups, or social media website (e.g. Facebook, Instagram, X etc.) until notified that the study is completed.3. Participant must be willing and able to comply with the study procedures (including diet) and visit schedules and must be able to follow verbal and written instructions. 4. Male and female participants aged 18 to 55 years (inclusive) at the time of informed consent. 5. Weighs at least 50 kg and body mass index (BMI) greater than or equal to 18.0 and less than 35.0 kg/m2 (inclusive) at screening. For the MAD cohort undergoing CSF, participants must weigh at least 50 kg. and BMI greater than or equal to 18.0 and less than 35.0 kg/m2. 6. Continuous nonsmoker who has not used nicotine containing products (including vaping) for at least 1 month prior to the first dosing and throughout the study, based on participant self-reporting. 7. Resting semi-supine systolic blood pressure 90 to 145 mmHg (inclusive) and diastolic blood pressure no higher than 90 mmHg at Screening and Check-In (D-2 or D-1) (to be taken after about 10 minutes in semi-supine position). 8. A 12-lead ECG with no clinically significant abnormalities as deemed by the Principal Investigator or delegate and Fredericia corrected QT interval (QTcF) interval = 450 milliseconds in males and 470 ms in females at Screening and Check-In (D-2 or D-1) (to be taken after about 10 minutes in semi-supine position). 9. Resting semi-supine pulse rate between 45 and 100 beats per minute at Screening and Check-In (D-2 or D-1). 10. Physical examination and laboratory investigations within the normal reference range, or if outside of the reference ranges, deemed not clinically significant in the opinion of the Principal Investigator or delegate. In the event the Principal Investigator or delegate deems a Grade 2 value at screening to be not clinically significant, the Principal Investigator or delegate will obtain approval for inclusion of participant from medical monitor and Sponsor (Clinical Lead) at Screening. Out-of-range labs (not within reference ranges) at Check-In (D-2 or D-1) are exclusionary if deemed clinically significant by the Principal Investigator or designee; exceptions include lab results for Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transferase (GGT) and Alkaline phosphatase (ALP), creatinine which would be exclusionary at Screening and Check-In (D-2 or D-1) if greater than 1.5x +/- upper limit of normal (ULN) of reference ranges regardless of clinical significance. 11. Screening EEG free of abnormalities, including data quality issues, that could confound interpretation of PD measures. 12. Willing to abstain from illicit drugs, alcohol, and nicotine products/tobacco use during study participation. 13. Participant must be willing to stay within the clinical research unit for the duration of the in-patient study period and return for all additional study visits as specified by the protocol. 14. Female participants who are sexually active with the opposite sex and of childbearing potential (defined as first menarche through post-menopause or permanent sterilization) must agree to use a highly effective method of birth control from time of screening and for 1 month following the last dose of study drug combined with the use of a condom by the male partner. 15. Female participants not of childbearing potential due to surgical sterilization (at least six weeks after hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) confirmed by medical history, or menopause. Menopausal women include women with spontaneous amenorrhea for at least 12 months without an alternative medical cause and a follicle-stimulating hormone level greater than 40 IU/L. 16. Male participants (post-pubertal unless permanently sterilized by bilateral orchidectomy or vasectomy with confirmed azoospermia) must agree to use male contraception (condom) combined with the use of a highly effective method of contraception by the female partner, and/or abstinence from time of screening and for 90 days following the last dose of study drug.
Exclusion criteria
1. History or presence of gastritis, gastrointestinal tract disorder, gastric bypass surgery, or hepatic disorder or other clinical condition which, in the opinion of the Principal Investigator or designee, may affect the absorption, distribution, metabolism, or elimination of study drug. History of cholecystectomy and diagnosis of Gilberts syndrome is also exclusionary.2. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, psychiatric disorder, or loss of consciousness (LOC) due to head injury greater than 30 minutes (Moderate Traumatic Brain Injury) as determined by the Principal Investigator (or designee). 3. Renal clearance defined as an average of less than 60ml/min using the Cockroft & Gault formula. 4. History or presence of alcohol or drug abuse within the past 2 years prior to Screening visit as determined by the Principal Investigator (or designee) and local guidance. Drug and alcohol tests will be conducted at Screening and on D-1 and may be repeated during the trial at the discretion of the PI. 5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds. 6. Risk of suicide according to the Principal Investigator’s or delegate’s clinical judgment (e.g., per CSSRS) or has made a suicide attempt in the previous year prior to Screening visit. 7. Unable to refrain from or anticipate the use of: a. Any (oral and non-oral) systemic drug, including prescription (with the exception of non-oral highly effective contraception) and nonprescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study, including the follow-up period. After the first dose of study drug, paracetamol/acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the Principal Investigator or designee. b. Alcohol, caffeinated and dietary products such as grapefruit, Seville oranges etc. c. Any product, remedy, supplement, or medication containing cannabidiol (CBD), Tetrahydrocannabinol (THC) or related compounds within 30 days prior to the first dosing and throughout the study, including the follow-up period. 8. Has been on a diet incompatible with the on-study diet with the phase of the study to which they are to enroll, in the opinion of the Investigator or designee, within the 30 days prior to the first dosing and throughout the study. 9. Participation in another clinical study within 30 days prior to the first dosing. The 30-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to D1 of the current study. If the previous investigational product has a long half-life, three months or five half-lives (whichever is longer) should have passed; participation in a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. 10. Receipt of vaccination (inclusive of influenza and SARS COV2) within 14 days of dosing (D1). 11. If male, the participant intends to donate sperm during the course of this study or for 90 days following the last dose of study drug. 12. If female, the participant is pregnant or intending to become pregnant before participating in this study, during the study, and within 1 month after last dose of the study drug; or intending to donate ova during such time period; or lactating. 13. Ovid employees or Investigator site personnel where the study is being conducted and/or their immediate family. Note: immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. 14. Participants who have Obstructive Sleep Apnea or any other conditions that can cause daytime somnolence, including individuals who work night shifts or who are otherwise are typically nocturnal. Any other contraindications for the EEG procedure per discretion of the PI. 15. Individuals who, in the opinion of the Principal Investigator or designee, should not participate in this study. 16. For the last cohort in MAD, participants that have experienced chronic headaches as these individuals are at higher risk due to CSF Lumbar Puncture procedure. 17. Taking medications that are CYP2C8 & CYP3A4 strong inhibitor or inducers; or a sensitive substrate for P-gp, BCRP or MATE1 & 2-K transporters, especially those with Narrow Therapeutic Index.
Outcome results
None listed