Healthy
Conditions
Brief summary
This is a Phase 1, FIH, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and PK characteristics of ENC1018 after single and multiple oral dose administration in healthy adult subjects. The study will be conducted in two parts: Part A -Single ascending Dose (SAD) and Part B - Multiple ascending dose (MAD). A Food Effect Cohort will be conducted within Part A. Part A is for the single dose use of IP, while Part B is once daily use for 14 consecutive days. Approximately 72 healthy adult subjects are planned to be enrolled. Each subject will be enrolled in only one cohort of either Parts A or B of the study, to receive only one dose regimen during the study. Part B may be initiated in parallel or prior to completion of Part A, at the discretion of Safety Review Committee (SRC), upon reviewing safety and plasma PK data.
Interventions
DRUGENC1018 for SAD
SAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (cohort A1-A6) to receive either ENC1018 or placebo. The investigational product (ENC1018 or placebo) will be administered orally as a single dose.
DRUGPlacebo for SAD
SAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (cohort A1-A6) to receive either ENC1018 or placebo. The investigational product (ENC1018 or placebo) will be administered orally as a single dose.
DRUGENC1018 for MAD
MAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (cohort B1-B3) to receive either ENC1018 or placebo. The investigational product (ENC1018 or placebo) will be administered orally for a total of 14 days.
DRUGPlacebo for MAD
MAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (cohort B1-B3) to receive either ENC1018 or placebo. The investigational product (ENC1018 or placebo) will be administered orally for a total of 14 days.
Sponsors
EnnovaBio Australia Pharmaceuticals Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female subjects of any ethnic origin, must be between 18 and 55 years of age inclusive. * Subject is in generally good health according to the Investigator's assessment as determined by medical history, physical examination, vital sign assessment, 12-lead ECG, and clinical laboratory evaluations. * Subject has a negative urine drug screen, cotinine screen, and alcohol breath test. * Nonsmoker * Subject has Body Mass Index 18.0 to 32.0 kg/m2 inclusive, and body weight from 50 - 100 kg for male subjects, 45 -100 kg for female subjects * Apply contraception methods for child-bearing potential subjects.
Exclusion criteria
* Have clinically relevant medical history or unstable hepatic, pulmonary, hematologicalor immunological disease making implementation of the protocol or interpretation of the study results difficult, or that would put the subject at risk by participating in the study, under the discretion of the Investigator. * Any disease or surgical procedure (including cholecystectomy) that may substantially affect IP absorption, distribution, metabolism, and excretion as judged by the Investigator * Any current active infections, including localized infections, or any recent history (within 1 week prior to IP administration) of active infections, cough, or fever; or a history of recurrent or chronic infections. * Dosing with any other investigational drug or therapy within 90 days prior to dosing. * Is positive for HBsAg,HCVAb, HIVAb, or tuberculosis. * Pregnant, breast-feeding and/or lactating women * Have received any live vaccines (bacterial or viral) within 12 weeks prior to Screening or intend to receive a live vaccine during the study period or within 30 days after the last dose of the IP.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluations of vital signs and changes from baseline will be assessed using descriptive statistics following ENC1018 administration | Day 1 through Day 8 (SAD) or 21 (MAD) | Vital signs include body temperature, respiratory rate, blood pressure, and pulse |
| Evaluations of 12-lead ECGs and changes from baseline will be assessed using descriptive statistics following ENC1018 administration | Day 1 through Day 8 (SAD) or 21 (MAD) | ECG parameters include heart rate, PR interval, QRS duration, QT interval, and QTcF interval |
| Number and type of treatment emergent adverse events (TEAE) following ENC1018 administration will be assessed using the latest version of Medical Dictionary for Regulatory Activities (MedDRA 25.0 or above) | Day 1 through Day 8 (SAD) or 21 (MAD) | — |
| Severity of TEAEs following ENC1018 administration will be assessed using categories as mild, moderate and severe | Day 1 through Day 8 (SAD) or 21 (MAD) | — |
| Evaluations of clinical laboratory and changes from baseline will be assessed using descriptive statistics following ENC1018 administration | Day 1 through Day 8 (SAD) or 21 (MAD) | Laboratory values include hematology, biochemistry, clinical chemistry, coagulation, and urinalysis |
| Evaluations of physical examinations and changes from baseline will be assessed using descriptive statistics following ENC1018 administration | Day 1 through Day 8 (SAD) or 21 (MAD) | Physical examination include assessments of the skin, cardiovascular, respiratory, gastrointestinal, and neurological systems |
Secondary
| Measure | Time frame |
|---|---|
| Maximum plasma concentration (Cmax) | SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose |
| Area under the plasma concentration versus time curve (AUC) | SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose |
| Time to maximum concentration (Tmax) | SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose |
| Terminal elimination half-life (t1/2) | SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose |
| Apparent oral plasma clearance (CL/F) | SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose |
| Apparent volume of distribution during the terminal phase (Vz/F) | SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose |
Countries
Australia
Outcome results
None listed