An ascending, single and multiple dose(s), double-blind, randomized, placebo controlled study assessing the safety, tolerability, and pharmacokinetics of ov329 in healthy male and female participants
- Conditions
- rare seizure disordersNeurological - Epilepsy
- Registration Number
- ACTRN12624000214538
- Lead Sponsor
- Ovid Therapeutics Australia Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 56
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 hormona; 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 hormona
Participants will be excluded from study enrollment if they meet any of the following 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.
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 is permitted.
2.Contraindications to magnetic resonance imaging (MRI) scanning, including but not limited to the presence of metallic surgical hardware, cardiac pacemaker, stents, mechanical heart valves, artificial limbs, brain stimulator devices, implanted drug pumps, cochlear implants, ocular implants or known metal fragments in eyes, exposure to shrapnel or metal filings, magnetic dental implants, or permanent retainer; history of clinically significant claustrophobia; participant had obtained a new tattoo within 30 days before first scan.
3.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.
4.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).
5.History or presence of alcohol or drug abuse within the past 2 years prior to screening visit as determined by the Investigator (or designee). .
6.History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds, including but not limited to vigabatrin.
7.Risk of suicide according to the Investigator’s clinical judgment (e.g., per Columbia Suicide Severity Rating Scale (C-SSRS)) or has made a suicide attempt in the previous year prior to Screening visit.
8.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-u; Participants will be excluded from study enrollment if they meet any of the following 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.
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 is permitted.
2.Contraindications to magnetic resonance imaging (MRI) scanning, including but not limited to the presence of metallic surgical hardware, cardiac pacemaker, stents, mechanical heart valves, artificial limbs, brain stimulator devices, implanted drug pumps, cochlear implants, ocular implants or known metal fragments in eyes, exposure to shrapnel or metal filings, magnetic dental implants, or permanent retainer; history of clinically significant claustrophobia; participant had obtained a new tattoo within 30 days before first scan.
3.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.
4.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).
5.History or presence of alcohol or drug abuse within the past 2 years prior to screening visit as determined by the Investigator (or designee). .
6.History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds, including but not limited to vigabatrin.
7.Risk of suicide according to the Investigator’s clinical judgment (e.g., per Columbia Suicide Severity Rating Scale (C-SSRS)) or has made a suicide attempt in the previous year prior to Screening visit.
8.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-u
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method