A Phase 1 trial assessing the Safety, Tolerability, and Pharmacokinetics of NIDO-361 in Healthy Male Subjects

INTERVENTION: This is a randomized, double‐blind, placebo controlled, ascending dose, multi‐cohort trial. The study will be conducted in two parts. Part A: A single ascending dose (SAD) part where dose levels will be evaluated in a sequential manner starting at the proposed lowest dose level in healthy male volunteers. 40 healthy male volunteers will be enrolled in a total of 5 cohorts. Each cohort will enrol 8 participants with 6 participants randomized to receive NIDO‐361 and 2 participants randomized to receive placebo. NIDO‐361 will be provided as an oral capsule. NIDO‐361 dose levels in the range of 75 to 500 mg are planned to be investigated. A single dose of NIDO‐361 or placebo will be administered on Day 1 followed by approximately 48 hours of safety, tolerability, and PK assessments. Participants will return approximately 1 week post study check‐out to complete follow‐up assessments. Part B: A multiple ascending dose (MAD) part where dose levels will be evaluated depending on SAD results in healthy male volunteers. Up to 24 healthy male volunteers will be enrolled in a total of 3 cohorts. Each cohort will enrol 8 participants with 6 participants randomized to receive NIDO‐361 and 2 participants randomized to receive placebo. A dose level will only be evaluated in Part B if determined to be safe and tolerable in Part A. NIDO‐361 or placebo will be administered daily (QD) for seven days (total of 7 doses) followed by approximately 48 hours of observation after last dose for safety assessments before discharge. Participants will return approximately 1 week post study check‐out to complete follow‐up assessments. Adherence to the intervention will be done via completion of drug accountability. CONDITION: Musculoskeletal ‐ Other muscular and skeletal disorders Neurological ‐ Other neurological disorders Spinal and bulbar muscular atrophy (SBMA); ; Spinal and bulbar muscular atrophy (SBMA) PRIMARY OUTCOME: To determine the safety and tolerability of NIDO‐361 when administered as a single oral dose in healthy male subjects. ; ; Safety Endpoints Include: Adverse Events (AEs), concomitant medications, physical examinations (including neurological examination, vital signs, weight, 12‐lead ECG), and clinical laboratory evaluations (including clinical chemistry, hematology, and urinalysis). [Adverse Events: Assessed daily at Screening, Day ‐1 (Check‐in), Day 1, Day 2, Day 3 (Check‐out), Day 8 (End of Study)/Early Termination Visit. Adverse Events will be graded using The Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. AEs will not be assessed daily from Days 3‐7. Following Day 3 (Check‐Out), participants will return to clinic on Day 8 and final study visit will be conducted, including review of any AEs participants may have experienced after being discharged from clinic on Day 3 (Check‐Out).; ; Concomitant Medications: Assessed daily at Screening, Day ‐1 (Check‐in), Day 1, Day 2, Day 3 (Check‐out), Day 8 (End of Study)/Early Termination Visit. Site staff will question participants on use of concomitant medications at study visits.; ; Physical Examinations: General appearance; head, ears, eyes, nose (HEENT), and throat examination, neck (including thyroid and nodes); cardiovascular, respiratory, gastrointestinal, renal, neurological, and musculoskeletal systems; and skin will be assessed. Complete physical examination will be performed at Screening and Day 8 (End of Study)/Early Termination Visit.. Symptom directed physical examination will be performed at Day ‐1 (Check‐in) and Day 3 (Check‐out).; ; Vital Signs: Blood pressure and heart rate are assessed using a sphygmomanometer and temperature by thermometer. Assessed at Screening, Day ‐1 (Check‐in), Day 1 Pre‐dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs and 12 hrs post‐dose, Day 2 24 hrs and 36 hrs post‐dose, Day 3 48 hrs post‐dose, Day 8 (End of Study)/Early Termination Visit.; ; Weight: Assessed using scales at Screening, Day ‐1 (Check‐in), Day 3 (Check‐out), Day 8 (End of Study)/Early Termination Visit.; ; 12‐Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day 1 Pre‐dose, 1 hr, 2 hrs, 4 hrs post‐dose, Day 2 24 hrs post‐dose, Day 3 48 hrs post‐dose, Day 8 (End of Study)/Early termination Visit.; ; Clinical Laboratory Evaluations (clinical chemistry, haematology and urinalysis): Blood and urine samples collected at Screening, Day ‐1 (Check‐in), Day 2 24 hrs post‐dose, Day 3 48 hrs post‐dose, Day 8 (End of Study)/Early Termination Visit. ] To determine the safety and tolerability of NIDO‐361 when administered as multiple oral doses at escalating dose levels in healthy male subjects. ; ; Safety Endpoints Include: Adverse Events (AEs), concomitant medications, physical examinations (including neurological examination, vital signs, weight, 12‐lead ECG), and clinical laboratory evaluations (including clinical chemistry, hematology, and urinalysis). [Adverse Events: Assessed daily at Screening, Day ‐1 (Check‐in), Day 1 to Day 8 (Treatment period), Day 9 (Check‐out), Day 15 (End of Study)/Early Termination Visit. Adverse Events will be graded using The Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. AEs will not be assessed daily from Days 9‐14. Following Day 9 (Check‐Out), participants will return to clinic on Day 15 and final study visit will be conducted, including review of any AEs participants may have experienced after being discharged from clinic on Day 9 (Check‐Out).; ; Concomitant Medications: Assessed daily at Screening, Day ‐1 (Check‐in), Day 1 to Day 8 (Treatment period), Day 9 (Check‐out), Day 15 (End of Study)/Early Termination Visit. Site staff will question participants on use of concomitant medications at study visits. ; ; Physical Examinations: General appearance; HEENT, neck (including thyroid and nodes); cardiovascular, respiratory, gastrointestinal, renal, neurological, and musculoskeletal systems; and skin will be assessed. Complete physical examination will be performed at Screening and Day 15 (End of Study)/Early Termination Visit. Symptom directed physical examination will be performed at Day ‐1 (Check‐in) and Day 9 (Check‐out).; ; Vital Signs: Blood pressure and heart rate are assessed using a sphygmomanometer and temperature by thermometer. Assessed at Screening, Day ‐1 (Check‐in), Day 1 Pre‐dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs, 6 hrs and 8 hrs post‐dose, Day 2 to Day 6: 6 hours post‐dose, Day 7 Pre‐dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs 6hrs and 8 hrs post‐dose, Day 8, Day 9 (Check‐out), Day 15 (End of Study)/Early Termination Visit.; ; Weight: Assessed using scales at Screening, Day ‐1 (Check‐in), Day 5 Pre‐dose, Day 9 (Check‐out), Day 15 (End of Study)/Early Termination Visit.; ; 12‐Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day 1 Pre‐dose, 1 hr, 2 hrs, 4 hrs post‐dose, Day 2 Pre‐dose, 24 hrs post‐dose, Day 5 Pre‐dose, Day 7 1 hr, 2 hr, 4 hrs post‐dose, Day 9 (Check‐out), Day 15 (End of Study)/Early Termination Visit.; ; Clinical Laboratory Evaluations (clinical chemistry, haematology and urinalysis): Blood and urine samples collected at Screening, Day ‐1 (Check‐in), Day 2 pre‐dose, Day 5 pre‐dose, Day 8, Day 15 (End of Study)/Early Termination Visit. ] SECONDARY OUTCOME: To determine the Pharmacokinetics (PK) of NIDO‐361 when administered as a single oral dose in healthy male subjects ; ; Plasma concentrations and derived PK parameters of NIDO‐361. AUClast, AUCtau, AUCinf, Cmax, Tmax, Cmin, t1/2 and other parameters will be derived and reported as appropriate[Plasma samples will be collected as follows: ; ; Day 1 Pre‐dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs and 12 hrs post‐dose ; Day 2 24 hrs and 36 hrs post‐dose ; Day 3 48 hrs post‐dose] To determine the PK of NIDO‐361 when administered as multiple oral doses at escalating dose levels in healthy male subjects ; ; Plasma concentrations and derived PK parameters of NIDO‐361. AUClast, AUCtau, AUCinf, Cmax, Tmax, Cmin, t1/2 and other parameters will be derived and reported as appropriate[Plasma samples will be collected as follows: ; ; Day 1 Pre‐dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs and 12 hrs post‐dose ; Day 2 24 hrs post‐dose from Day 1 ; Day 7 Pre‐dose, 15 min, 30 min, 1 hr, 2 hrs, 4 hrs, 6 hrs and 8 hrs post‐dose ; Day 8 24 hrs from the time of dosing on Day 7] INCLUSION CRITERIA: To be included in this study, each individual must satisfy all the following criteria: 1. The subject is a healthy male adult, aged 18 to 55 years, inclusive, at the time of consent. 2. The subject weighs at least 45 kg (99 lb.) and has a body mass inde X(BMI) between 18.0 and 32.0 kg/m2, inclusive, at Screening. 3. In the opinion of the Investigator, the subject is capable of understanding and complying with protocol requirements. 4. The subject has documented ability to understand the written study informed consent form (ICF) and consent and has provided signed written informed consent prior to any study procedures. 5. A male subject who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from the signing of the informed consent throughout the duration of the study and 90 days from the last dose. In addition, male subjects must be willing to forgo sperm donation for the durat