None listed
Conditions
Brief summary
This phase 1 study is a randomized, placebo-controlled, double-blind, trial of an oral drug called NB-4746 vs. placebo in normal healthy volunteers. The study will assess the safety and tolerability in single and multiple ascending dose cohorts.
Interventions
This is a single center, double-blind randomized placebo-controlled study to assess the safety, tolerability and pharmacokinetics of NB-4746 in healthy volunteers.
A total of 66 subjects will be enrolled sequentially into 6 ascending single dose and 3 ascending multiple dose cohorts. Subjects will only be allowed to enrol in one cohort.
Part A - Single Escalating Dose:
Study participants will be randomly assigned to receive a single dose of NB-4746 or placebo administered as an oral solution o
This is a single center, double-blind randomized placebo-controlled study to assess the safety, tolerability and pharmacokinetics of NB-4746 in healthy volunteers. A total of 66 subjects will be enrolled sequentially into 6 ascending single dose and 3 ascending multiple dose cohorts. Subjects will only be allowed to enrol in one cohort. Part A - Single Escalating Dose: Study participants will be randomly assigned to receive a single dose of NB-4746 or placebo administered as an oral solution on day 1. There will be 6 ascending dose cohorts in Part A with 7 participants per cohort. The proposed dose levels for cohorts 1 through to 6 are 50, 100, 175, 300, 450 and 600mg as a single oral dose. Participants must fast for at least 10 hours prior to administration. Administration will occur under supervision. Sentinel dosing will occur within each cohort, whereby on Day 1, the first 2 subjects will receive NB-4746 or placebo as assigned per the 1:1 randomization schedule. A minimum of 48 hours following sentinel dosing, following safety assessment by the Principal Investigator (PI), the remaining 5 subjects in each cohort will be randomly assigned to receive NB-4746 or placebo in a 4:1 ratio. A Safety Review Committee (SRC) will review the safety and 24-hour PK data together in a blinded manner and approve or deny escalation to the next higher dose. Each follow-on cohort will not commence dosing until a minimum of 6 subjects from the prior cohort have completed their in-house/confinement period. Part B - Multiple Ascending Doses: Study participants will be randomly assigned to receive multiple doses of NB-4746 or placebo administered as an oral solution for 10 days. NB-4746 or placebo will be administered once on day 1 (single dose in the morning (AM)), twice a day (BID) 12 hours apart on days 2 to 9, and a single dose in the morning (AM) of day 10. There will be 3 ascending dose cohorts in Part B with 8 participants per cohort. The proposed dose levels for cohorts 1 through to 3 are 100, 250 and 400mg, but may be revised depending on the results of part A. Participants must fast for at least 10 hours prior to administration. Administration will occur under supervision. Sentinel dosing will occur within each cohort, whereby on Day 1, the first 2 subjects will receive NB-4746 or placebo for 10 days in a 1:1 randomization ratio. A minimum of 48 hours following the second (PM) dose of study drug on Day 3 in these 2 “sentinel” subjects and following safety assessment by the PI, the remaining 6 subjects in each cohort will be randomly assigned to receive NB-4746 or placebo for 10 days in a 5:1 ratio starting on day 6 with the morning dose. Prior to the initiation the second and subsequent dosing cohorts, the SRC will review the blinded safety and PK data (if available) from a minimum of 3 days of dosing to determine if a dose escalation to the next higher can occur. Each follow-on cohort will not commence dosing until a minimum of 7 subjects from the prior cohort have completed their in-house/confinement period. Part C - Cerebrospinal Fluid (CSF) cohort Part C is a standalone cohort to estimate central nervous system (CNS) exposure of NB-47476 by measuring CSF concentrations. All participants in the CSF cohort will receive the study drug (NB-4746). Upon confirmation of eligibility, approximately 4 participants will receive a single dose of study drug on Day 1, at the same dose as SAD cohort 4 (250mg). All participants will remain at the research site from days -1 to day 4 post-dose, and CSF sampling will occur on day 1.
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
- Male and post-menopausal females aged >/=18 years and < /=65 years old at the time of signing informed consent. - Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (ECG). - Nonsmoker and/or ex-smoker who has discontinued smoking and/or the use of nicotine containing products for at least 3 months prior to first dose of study drug. - Body mass index within the range 18 to 30 kg/m2 inclusive. - 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 subjects (whether postmenopausal or surgically sterile) must use a barrier form (e.g., condom) of contraception until the end of the study visit (EOS) or 7 days after the last dose of study drug in case of early termination. - 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 end of the study visit (EOS) or 7 days after the last dose of study drug in case of early termination.
Exclusion criteria
- 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. - Subjects with a history of pancreatitis or with prior cholecystectomy. - Any significant chronic medical illness, as determined by the investigator. - 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 may be enrolled in the study at the discretion of the Investigator. - The subject has a history of severe drug allergy or hypersensitivity or food allergy, including anaphylaxis. - The subject has had surgery or trauma with significant blood loss within the last 3 months prior to the first dose of study drug. - The subject has donated more than 1 unit (500 mL) of blood within 4 weeks prior to the first dose of study drug. . - Abnormal vital signs that are considered to be clinically significant by the investigator. - 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. - Breast cancer within the past 10 years. - Clinically significant laboratory abnormality at the screening visit or before the administration of the first dose of study drug. - Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of asymptomatic gallstones). - QTcF interval (QT with Fredericia’s correction) > 450 msec in males and > 470 msec in females (based on the mean of triplicate measurements taken at screening). - Females of childbearing potential, irrespective of contraceptive measures taken. - Inability to tolerate oral medications. - Past or intended use of over-the-counter or prescription medication (including herbal medications) within 14 days before dosing. - Live vaccine(s) within 1 month before Screening or plans to receive such vaccines during the study. - Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) before dosing. - 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 Screening. - Positive prestudy drug or alcohol screen. - Positive human immunodeficiency virus (HIV) or hepatitis C antibody test (HCV), or hepatitis B surface antigen (HBsAg) at screening or 3 months before enrollment. - 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 subjects and > 3 drinks/day for male subjects. - Use of tobacco products (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco) confirmed by a positive cotinine test on Day -1. - Regular use of known drugs of abuse or a history of drug abuse within 12 months prior to screening.
Outcome results
None listed