None listed
Conditions
Brief summary
OV329 [(S)-3-amino-4-(difluoromethylene) cyclopent-1-ene-1-carboxylic acid hydrochloride salt] is a gamma aminobutyric acid (GABA) aminotransferase (GABA-AT) inhibitor that is being developed as an antiseizure medication for seizure disorders in adults and pediatric patients. Part A will consist of up to 2 cohorts, comprising 8 participants each. Dosing will be initiated at 7 mg/day. Subsequent cohorts will be dosed as recommended by the Data Review Committee (DRC) based on the safety, tolerability and PK of OV329 from the previous cohort. Part B will consist of 2 planned cohorts comprising 8 participants each. Subsequent cohorts will be dosed as recommended by the DRC based on the safety, tolerability and PK of OV329 from the previous cohort (based on review of the Day 30 data, including ophthalmological assessments). Participants will be dosed for a total of 7 days. Part C will consist of 1 planned cohort comprising approximately 20 participants, with a minimum of 6 but up to 8 participants receiving 7mg OV329 daily and a minimum of 6 but maximum of 8 participants receiving another dose level of OV329 cleared in Parts A and B. A minimum of 3 but up to 4 participants will receive placebo. Participants will be dosed for a total of 84 days.
Interventions
Phase 1, single center, randomized, double-blind, placebo controlled, inpatient study of the safety and tolerability of single and multiple ascending oral dose(s) of OV329 in healthy adult males and non-pregnant or non-breastfeeding female participants. The study will be conducted in two parts: Part A, single ascending dose (SAD); and Part B, multiple ascending doses (MAD). Summary of data from completed cohorts in Part A and any additional information to support the study plan for Part B will b
Phase 1, single center, randomized, double-blind, placebo controlled, inpatient study of the safety and tolerability of single and multiple ascending oral dose(s) of OV329 in healthy adult males and non-pregnant or non-breastfeeding female participants. The study will be conducted in two parts: Part A, single ascending dose (SAD); and Part B, multiple ascending doses (MAD). Summary of data from completed cohorts in Part A and any additional information to support the study plan for Part B will be reviewed by the Data Review Committee (DRC). Any doses tested in Part B MAD will first be cleared for safety in Part A SAD. Within each cohort of Part A and Part B, a sentinel group comprising two participants (one receiving active treatment and one receiving placebo) will be randomized and dosed ahead of the remaining participants. These individuals will undergo close monitoring for 48 hours post-dose during the in-unit phase of Part A (Day 3) and for 9 days during the inpatient and outpatient follow-up period up to Day 14 of Part B. All safety data will be reviewed by the Principal Investigator who will determine if it is safe to proceed with the rest of the cohort. Then, the remaining 6 participants will be dosed, and the safety assessment of these 6 participants will proceed as planned. The starting dose for Part A will be 7mg Part A and Part B will be oral tablets which are dosed once in Part A and 7 days in Part B with the respective follow up noted above and dosed within the Phase I unit. As this is completed as an inpatient study and therefore will Study team at the unit will oversee each dosing
Phase 1, single center, randomized, double-blind, placebo controlled study of the safety and tolerability of single, multiple and long-term ascending oral dose(s) of OV329 in healthy adult males and non-pregnant or non-breastfeeding female participants. The study will be conducted in three parts: Part A, single ascending dose (SAD); Part B, multiple ascending doses (MAD) and Part C Long-Term (12 week) dosing. Summary of data from completed cohorts in Part A and any additional information to supp
Phase 1, single center, randomized, double-blind, placebo controlled study of the safety and tolerability of single, multiple and long-term ascending oral dose(s) of OV329 in healthy adult males and non-pregnant or non-breastfeeding female participants. The study will be conducted in three parts: Part A, single ascending dose (SAD); Part B, multiple ascending doses (MAD) and Part C Long-Term (12 week) dosing. Summary of data from completed cohorts in Part A and any additional information to support the study plan for Part B will be reviewed by the Data Review Committee (DRC). Any doses tested in Part B MAD will first be cleared for safety in Part A SAD. Part C will include 2 doses cleared in Parts A and B. Within each cohort of Part A and Part B, a sentinel group comprising two participants (one receiving active treatment and one receiving placebo) will be randomized and dosed ahead of the remaining participants. These individuals will undergo close monitoring for 48 hours post-dose during the in-unit phase of Part A (Day 3) and for 9 days during the inpatient and outpatient follow-up period up to Day 14 of Part B. All safety data will be reviewed by the Principal Investigator who will determine if it is safe to proceed with the rest of the cohort. Then, the remaining 6 participants will be dosed, and the safety assessment of these 6 participants will proceed as planned. The starting dose for Part A will be 7mg. Part C will consist of 1 planned cohort comprising of approximately 20 participants, with a minimum of 6 but up to 8 participants receiving 7mg of OV329 daily, a minimum of 6 but up to 8 participants receiving another dose level of daily OV329 cleared in parts A and B, and a minimum of 3 but up to 4 participants using placebo. Participants will be dosed for a total of 84 days. Part A and Part B will be oral capsules which are dosed once in Part A and 7 days in Part B with the respective follow up noted above and dosed within the Phase I unit. As this is completed as an inpatient study and therefore will Study team at the unit will oversee each dosing. Part C will be oral capsules dispensed in a blister pack for repeated once daily oral dosing. Participants will be instructed to self-administer the study medication at home and compliance will be assessed by a paper diary log and study drug reconciliation. Participants will return for clinic visits on days 15, 29 and 57 where their compliance will be assessed, daily dose administered in the clinic and new study drug dispensed to take home.
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
Participants are eligible to be included in the study only if they meet all the following criteria and none of the exclusion 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, Twitter 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 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 at screening. 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 supine systolic blood pressure 90 to 145 mmHg (inclusive) and diastolic blood pressure no higher than 90 mmHg at Screening and Day -1 (to be taken after about 10 minutes in supine position). 8. A 12-lead ECG with no clinically significant abnormalities as deemed by the investigator and Fredericia corrected QT interval (QTcF) interval less than or equal to 450 milliseconds at Screening and Day -1 (to be taken after about 10 minutes in supine position). 9. Resting supine pulse rate between 45 and 100 beats per minute at Screening and Day -1. 10. Normal 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 investigator. In the event the investigator deems a Grade 2 value at screening to be not clinically significant, the investigator 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 Day -1 are exclusionary if deemed clinically significant by the investigator or designee; exceptions include lab results for Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transferase (GGT) and Alkaline phosphatase (ALP), which would be exclusionary at Screening and Day -1 if greater than 1.5x +/- upper limit of normal (ULN) of reference ranges regardless of clinical significance. 11. Willing to abstain from illicit drugs, alcohol, and nicotine products/tobacco use during study participation. 12. 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. 13. 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. Highly effective contraceptive methods are as follows and must be in use for at least 90 consecutive days before drug administration: - Intrauterine device - Intrauterine hormone-releasing system - Bilateral tubal occlusion - Intravaginal or transdermal hormonal contraception - Injectable or implantable contraceptive systems, including progestogen-only hormonal contraception associated with inhibition of ovulation - Vasectomized or same sex partner - Abstinence (see note below) NOTE: Double barrier is not considered highly effective per Clinical Trials Facilitation and Coordination Group contraceptive guidance. Oral contraceptives alone (without a highly effective contraceptive listed above) is not permissible. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of this clinical trial and the preferred and usual lifestyle of the subject. 14. 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 either: - Spontaneous amenorrhea for at least 12 months without an alternative medical cause OR - Spontaneous amenorrhea for six to 12 months and a follicle-stimulating hormone level greater than 40 mIU/mL 15. 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 male abstinence from time of screening and for 90 days following the last dose of study drug (t half life estimated to be less than one day based on preliminary data after SAD)
Exclusion criteria
1. Any past or current history of an ophthalmologic condition that is congenital, infectious, genetic or acquired, that required medication, surgery or ongoing care, including: reduced visual acuity, reduced visual field, cataract, glaucoma, elevated intraocular pressure, uveitis, vitritis, optic neuritis, optic atrophy, optic nerve edema, papilledema, neuroretinitis, any inflammatory optic nerve or retinal condition (e.g., Multiple Evanescent White Dot Syndrome [MEWDS], Familial Exudative Vitreoretinopathy [FEVR], Acute Zonal Occult Outer Retinopathy [AZOOR]), any inflammatory or autoimmune condition of the orbit (e.g. thyroid eye disease, idiopathic orbital inflammatory syndrome, Rosai-Dorfman, IgG4, etc.), retinal detachment, retinal edema, retinal or optic nerve hemorrhage, maculopathy, diabetic retinopathy, retinal artery or vein occlusion, retinal degeneration, congenital retinal abnormality, glaucoma, corneal laceration or trauma, choroidal neovascularization, age related macular degeneration, pathologic myopia, and optic nerve or retinal coloboma, that is clinically relevant/significant per PI discretion. Of note, the following ophthalmologic conditions if resolved > 6 months ago (i.e., prior to Screening) are permitted: conjunctivitis (viral, bacterial or allergic) and chalazion. Reduced visual acuity secondary to refractive error that is corrected to normal with glasses/contacts/refractive laser surgery is permitted. Normal visual acuity can include 0.2 logMar of Normal (20/20, 20/25 and 20/30) which is equivalent to 6/6 to 6/9. 2. History or presence of gastritis, gastrointestinal tract disorder, gastric bypass surgery, or hepatic disorder or other clinical condition which, in the opinion of the Investigator or designee, may affect the absorption, distribution, metabolism, or elimination of study drug. And also, recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks prior to first dosing. 3. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee). 4. History or presence of alcohol or drug abuse within the past 2 years prior to Screening visit as determined by the Investigator (or designee). 5. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds, including but not limited to vigabatrin. 6. Risk of suicide according to the Investigator’s clinical judgment (e.g., per C-SSRS) 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 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, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the 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, 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) within14 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. Individuals who, in the opinion of the Investigator or designee, should not participate in this study.
Outcome results
None listed