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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ENC1018 for SAD | Experimental | 6 of out 8 subjects per cohort will be randomized to receive ENC1018 |
|
| Placebo for SAD | Placebo Comparator | 2 of out 8 subjects per cohort will be randomized to receive placebo |
|
| ENC1018 for MAD | Experimental | 6 of out 8 subjects per cohort will be randomized to receive ENC1018 |
|
| Placebo for MAD | Placebo Comparator | 2 of out 8 subjects per cohort will be randomized to receive placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ENC1018 for SAD | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Laboratory values include hematology, biochemistry, clinical chemistry, coagulation, and urinalysis | 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 | Physical examination include assessments of the skin, cardiovascular, respiratory, gastrointestinal, and neurological systems | Day 1 through Day 8 (SAD) or 21 (MAD) |
| Evaluations of vital signs and changes from baseline will be assessed using descriptive statistics following ENC1018 administration | Vital signs include body temperature, respiratory rate, blood pressure, and pulse | Day 1 through Day 8 (SAD) or 21 (MAD) |
| Evaluations of 12-lead ECGs and changes from baseline will be assessed using descriptive statistics following ENC1018 administration | ECG parameters include heart rate, PR interval, QRS duration, QT interval, and QTcF interval | Day 1 through Day 8 (SAD) or 21 (MAD) |
| Measure | Description | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philip Ryan, Doctor | Nucleus Network Pty Ltd. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nucleus Network Pty Ltd. | Melbourne | Victoria | 3004 | Australia |
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| Placebo for SAD | Drug | 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. |
|
| ENC1018 for MAD | Drug | 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. |
|
| Placebo for MAD | Drug | 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. |
|
| 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 |
| ID | Term |
|---|---|
| D064346 | Sagittal Abdominal Diameter |
| C110804 | mycophenolic adenine dinucleotide |
| ID | Term |
|---|---|
| D049628 | Body Size |
| D001837 | Body Weights and Measures |
| D001824 | Body Constitution |
| D010808 | Physical Examination |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D000886 | Anthropometry |
| D008919 | Investigative Techniques |
| D010829 | Physiological Phenomena |
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