A Phase 1, First-in-Human, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Escalating Single and Multiple Doses of ENC1018 in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- ENC1018 for SAD
- Conditions
- Healthy
- Sponsor
- EnnovaBio Australia Pharmaceuticals Pty Ltd
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- Severity of TEAEs following ENC1018 administration will be assessed using categories as mild, moderate and severe
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
ENC1018 for SAD
6 of out 8 subjects per cohort will be randomized to receive ENC1018
Intervention: ENC1018 for SAD
Placebo for SAD
2 of out 8 subjects per cohort will be randomized to receive placebo
Intervention: Placebo for SAD
ENC1018 for MAD
6 of out 8 subjects per cohort will be randomized to receive ENC1018
Intervention: ENC1018 for MAD
Placebo for MAD
2 of out 8 subjects per cohort will be randomized to receive placebo
Intervention: Placebo for MAD
Outcomes
Primary Outcomes
Severity of TEAEs following ENC1018 administration will be assessed using categories as mild, moderate and severe
Time Frame: 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
Time Frame: Day 1 through Day 8 (SAD) or 21 (MAD)
Laboratory values include hematology, biochemistry, clinical chemistry, coagulation, and urinalysis
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)
Time Frame: Day 1 through Day 8 (SAD) or 21 (MAD)
Evaluations of physical examinations and changes from baseline will be assessed using descriptive statistics following ENC1018 administration
Time Frame: Day 1 through Day 8 (SAD) or 21 (MAD)
Physical examination include assessments of the skin, cardiovascular, respiratory, gastrointestinal, and neurological systems
Evaluations of vital signs and changes from baseline will be assessed using descriptive statistics following ENC1018 administration
Time Frame: 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
Time Frame: Day 1 through Day 8 (SAD) or 21 (MAD)
ECG parameters include heart rate, PR interval, QRS duration, QT interval, and QTcF interval
Secondary Outcomes
- 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)
- Maximum plasma concentration (Cmax)(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)
- 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)
- 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)