None listed
Conditions
Brief summary
This study is a prospective, randomized, double-blind, placebo controlled, two-part, Phase 1 clinical study to evaluate the safety, tolerability, PK and PD of oral single-ascending doses (SAD) and oral multiple-ascending doses (MAD) of AZ-3102 in healthy female and male subjects (between 18 and 55 years of age, inclusive), with body mass index between 18 and 30 kg/m^2. The study consists of 2 parts: SAD and MAD. A total of 88 healthy subjects are planned for the study: Part 1 (SAD): 52 subjects (6 cohorts); Part 2 (MAD): 36 subjects (3 cohorts). In the MAD part all subjects will receive once daily dosing of AZ-3102 over 14 days.
Interventions
"Up to 88 healthy men or women will be enrolled in this study. There will be two parts to the study.
In the first part of the study approximately 52 healthy men and women will be enrolled in up to 6 single ascending dose cohorts comprising 8 participants each. Participants within each cohort will be randomised to receive a single dose of either oral AZ-3102 (6 participants) or oral placebo (2 participants). A total of 12 subjects will be enrolled in one of the 6 cohorts (9 randomised to AZ-3
"Up to 88 healthy men or women will be enrolled in this study. There will be two parts to the study. In the first part of the study approximately 52 healthy men and women will be enrolled in up to 6 single ascending dose cohorts comprising 8 participants each. Participants within each cohort will be randomised to receive a single dose of either oral AZ-3102 (6 participants) or oral placebo (2 participants). A total of 12 subjects will be enrolled in one of the 6 cohorts (9 randomised to AZ-3102, 3 to placebo) All cohorts will be started with sentinel dosing. The study drug will be administered under direct observation in the Phase 1 unit. The starting doses for the first cohort will be 1 mg. In the following cohorts, dose will be escalated based on plasma pharmacokinetic (PK), safety and tolerability In the second part of the study approximately 36 healthy men and women will be enrolled into up to 3 multiple ascending dose cohorts comprising 12 participants each. Participants within each cohort will be randomised to receive multiple doses of either oral AZ_3102 (9 participants) or oral placebo (3 participants). Each dose regimen will be administered for 14 days dosing every 24 hours The doses for each cohort will be selected based on available PK, safety and tolerability data from the Single ascending dose (SAD) part and previous Multiple ascending dose (MAD) cohorts" for SAD component: It is planned that the maximum possible dose will be 40mg AZ3102, however it is yet to be determined. mode of administration: Oral capsules. To assess or monitor adherence to the intervention: both checks of the returned bottle and mouth checks are conducted to monitor adherence to the protocol
Sponsors
Azafaros
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 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subjects must be able and willing to give written informed consent and are willing to comply with the requirements and restrictions of the study. 2. Subject must be at least 18 years of age at Screening and maximum 55 years of age on date of first dose. 3. A male participant with a female partner of childbearing potential is eligible if he agrees to follow the contraceptive guidance. 4. Female subject is eligible if she is not a woman of childbearing potential (WOCBP) OR, if she is a WOCBP, she agrees to follow the contraceptive guidance. 5. Body mass index (BMI) of greater than or equal to 18.0 kg/m2 and less than or equal to 30.0 kg/m2 at Screening. 6. Healthy as determined by the Investigator, based upon a medical evaluation including medical history, physical examination, clinical laboratory tests, and 12-lead ECG performed at Screening. Out of range values can be repeated once. 7. Subjects must be willing to use adequate contraception, and to refrain from sperm donation, from the time of dosing until 90 days after the last dose of study drug. 8. Subjects that undergo CSF collection: subjects must be willing and able to undergo CSF collections using a lumbar puncture.
Exclusion criteria
Subjects will be excluded if they meet any of the following criteria: 1. Prior or ongoing medical condition, medical history, physical findings, ECG findings, laboratory, or vital signs abnormality that, in the Investigator’s opinion, could adversely affect the safety of the subject. 2. History of clinically significant drug allergies. 3. Alkaline phosphatase, aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT) level greater than 1.5 x upper limit of normal (ULN) at Screening. 4. Creatinine clearance less than 90 mL/min (according to Cockcroft-Gault formula). 5. Total bilirubin greater than 1.5 x ULN (isolated bilirubin greater than 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is less than 35%). 6. Platelet count less than 100 x 10^9/L 7. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 21 days or five half-lives (whichever is longer) before the first dose of study drug, unless in the opinion of the Investigator and Sponsor’s Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. 8. ECG with an average of triplicate QTcF interval greater than 450 msec. 9. A female subject who has a positive pregnancy test at screening or Day -1, or is breastfeeding. 10. Positive urine drug screen or positive alcohol breath test at Screening or Day -1. 11. History of alcohol abuse within 6 months prior to Screening, defined as an average weekly intake of greater than 10 units. 12. Positive urine cotinine at screening or Day -1. 13. Positive result at screening for any of the following infectious disease tests: hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), human immunodeficiency virus antigen and antibody (HIV Ag, HIV Ab) 14. History of seizure, head trauma, loss of consciousness, symptomatic orthostatic hypotension (e.g. postural syncope). 15. Donation of 500 mL or more blood within 3 months prior to the first dose of study drug; or any amount of plasma in the 7 days prior to Screening; or any amount of platelets in the 42 days prior to Screening. 16. Receipt of an investigational product within 90 days prior to the first dose of study drug or exposure to more than four new chemical entities within 12 months prior to the first dose of study drug. 17. CSF subjects: Any condition or anatomic abnormality that would preclude spinal CSF collection by lumbar puncture or contraindications to lumbar puncture such as papilledema/raised intracranial pressure, infection near lumbar puncture site. 18. Evidence of suicidal ideation with intent (Type 4-5) on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening (Part 2 MAD only). 19. Attempted suicide attempt in the 6 months before Screening. 20. Employee or immediate family member (eg, spouse, parent, child, sibling) of clinical research unit (CRU) or of the Sponsor.
Outcome results
None listed