None listed
Conditions
Brief summary
This Phase 1 study is testing a new drug called NB-9402. The study drug NB-9402 is being developed by Nura Bio Inc. as a potential treatment for diseases of the nervous system. This study will assess the safety and tolerability of NB-9402 when given as single and multiple oral doses in healthy adult volunteers.
Interventions
Part A - Single Ascending Dose (SAD).
5 cohorts of 7 participants each will receive either NB-9402 or placebo administered as a single dose oral liquid (via oral syringe) followed by a water rinse and swallow. Dose levels planned are 50mg, 125mg, 250mg, 400mg and 500mg. Each participant will be assigned to receive a single dose of NB-9402 or placebo on Day 1 in a 5:2 randomization ratio (i.e., 5 to NB-9402 and 2 to placebo). Sentinel dosing will occur within each cohort, whereby on Day 1, the fi
Part A - Single Ascending Dose (SAD). 5 cohorts of 7 participants each will receive either NB-9402 or placebo administered as a single dose oral liquid (via oral syringe) followed by a water rinse and swallow. Dose levels planned are 50mg, 125mg, 250mg, 400mg and 500mg. Each participant will be assigned to receive a single dose of NB-9402 or placebo on Day 1 in a 5:2 randomization ratio (i.e., 5 to NB-9402 and 2 to placebo). Sentinel dosing will occur within each cohort, whereby on Day 1, the first 2 participants will receive NB-9402 or placebo as assigned per a 1:1 randomization ratio. A minimum of 24 hours following sentinel dosing and following safety assessment by the PI, the remaining 5 participants in each cohort will be randomly assigned to receive NB-9402 or placebo in a 4:1 ratio. All participants will be confined in the Clinical Research Unit (CRU) from Days 1 to 4. Part B - Multiple Ascending Dose (MAD). 3 cohorts of 8 participants each will receive either NB-9402 or placebo daily for 10 days administered as an oral liquid (via oral syringe), followed by a water rinse and swallow. Dose levels planned are 125mg, 250mg and 400mg. Sentinel dosing will occur within each cohort, whereby on Day 1, the first 2 participants will receive NB-9402 or placebo for 10 days in a 1:1 randomization ratio. A minimum of 24 hours following the dose of study drug on Day 3 in these 2 “sentinel” participants and following safety assessment by the PI, the remaining 6 participants in each cohort will be randomly assigned to receive NB-9402 or placebo for 10 days in a 5:1 ratio. Participants in Part B will be confined in the CRU from Days -1 to 13. Each SAD cohort will occur approximately 3 weeks apart, which will allow time for the Safety Review Committee (SRC) meeting to be conducted after each cohort. MAD1 can start after SAD3 has been completed. Each MAD cohort will occur approximately 4 weeks apart, which will allow time for the SRC meeting to be conducted after each cohort.
Sponsors
Nura Bio Inc
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participant must be >/= 18 years and < /= 65 years old at the time of signing informed consent. 2. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (ECG) obtained within 28 days before study drug administration. (note: bile acid assay results are not required to confirm eligibility). 3. Baseline laboratory test values within reference ranges based on the blood and urine samples taken at screening and on Day-1 (i.e. before administration of the first dose of study drug). Out of normal ranges values may be accepted by the Investigator, if not clinically significant. 4. Nonsmoker and/or ex-smoker who has discontinued smoking and/or use of nicotine-containing products for at least 3 months prior to the first dose of study drug, confirmed by a negative cotinine test at screening and Day -1. Social smoking is permitted; however, participants must have a negative cotinine test at both screening and on Day -1. Repeat testing may be performed at the Investigator's discretion. 5. Ability to communicate well with the Investigator, in the local language, and to understand and comply with the requirements of the study. 6. Body mass index (BMI) within the range 18 to 32 kg/m2 (inclusive). 7. Females must be either postmenopausal for >/=1 year (or with FSH >/=40 mIU/mL at screening if postmenopausal for < 1 year) or surgically sterile (having undergone bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months. However, to protect against the transfer of the study drug in any bodily fluids, male partners of female participants (whether postmenopausal or surgically sterile) must use a barrier form (e.g., condom) of contraception until the EOS visit or 7 days after the last dose of study drug in case of early termination. 8. Males with female partners of childbearing potential will agree to use barrier contraceptive (i.e., condom) and their female partners must use a highly effective method of contraception from screening to 90 days after the last dose of study drug. Males must also refrain from sperm donations during this time period. Males who are abstinent will not be required to use a contraceptive method unless they become sexually active. Males in a same sex relationship must also use a barrier form of contraception against the transfer of the study drug in any bodily fluids until the EOS visit or 7 days after the last dose of study drug in case of early termination.
Exclusion criteria
1. History or presence of significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. 2. Any significant chronic medical illness, as determined by the Investigator. 3. Mentally or legally incapacitated, has significant emotional problems at screening or expected during the conduct of the study, or has a history of a clinically significant psychiatric disorder within the last 5 years. Note: normal healthy volunteers who have had situational depression without suicidal ideation or behavior may be enrolled in the study at the discretion of the Investigator. 4. The participant has a history of severe drug allergy or hypersensitivity or food allergy, including anaphylaxis. 5. The participant has had surgery or trauma with significant blood loss within the last 3 months prior to the first dose of study drug. 6. The participant has donated more than1 unit (500 mL) of blood within 4 weeks prior to the first dose of study drug. 7. Fever (body temperature >38°C) or symptomatic viral or bacterial infection within 2 weeks prior to screening. 8. Any abnormal vital signs -at screening or before the first administration of study drug- considered to be clinically significant by the Investigator. 9. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Fully resected basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with no evidence of recurrence for 1 year are permitted. 10. Breast cancer within the past 10 years. 11. Alanine transaminase (ALT) or aspartate aminotransferase (AST) > 1.5 x upper limit of normal. 12. Bilirubin > 1.5 x upper limit of normal (isolated bilirubin > 1.5 x upper limit of normal is acceptable if bilirubin is fractionated and direct bilirubin < 35%). 13. Any other clinically significant laboratory abnormality at the screening visit or before the administration of the first dose of study drug. 14. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 15. QTcF interval (QT with Fridericia’s correction) > 450 msec in males and > 470 msec in females (based on the mean of triplicate measurements taken at screening). 16. Females of childbearing potential, irrespective of contraceptive measures taken. 17. Inability to tolerate oral medications. 18. Past or intended use of over-the-counter or prescription medication [including herbal medications] within 14 days before dosing. 19. Live vaccine(s) within 1 month before screening or plans to receive such vaccines during the study. 20. Treatment with biologic agents (such as monoclonal antibodies, including marketed drugs) within 3 months or 5 half-lives (whichever is longer) before dosing. 21. Current participation in any other investigational drug study or receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) before Day -1 for all Parts. 22. Positive prestudy drug or alcohol screen. Retesting will be allowed in the event a false positive outcome is suspected. 23. Positive human immunodeficiency virus (HIV) or hepatitis C antibody test (HCV), or hepatitis B surface antigen (HBsAg) at screening or 3 months before enrollment. 24. Regular alcohol consumption within 6 months before the study defined, current evidence of substance dependence or self-reported alcoholic intake > 2 drinks/day for female participants and > 3 drinks/day for male participants. 25. Use of tobacco products (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco) confirmed by a positive cotinine test. 26. Regular use of known drugs of abuse or a history of drug abuse within 12 months prior to screening. 27. Sensitivity to any of the study drug, or components thereof, or drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation in the study.
Outcome results
None listed