Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03029741 | Bioavailability of AZD0284 and IV Microtracer Study | PHASE1 | COMPLETED | 6 | — | — | Feb 21, 2017 | Mar 23, 2017 | Apr 13, 2017 | 1 | United Kingdom |
| NCT02976831 | Study to Assess the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of AZD0284 in Healthy Subjects | PHASE1 | COMPLETED | 83 | — | — | Dec 9, 2016 | May 30, 2017 | Jun 14, 2017 | 1 | United Kingdom |
Absolute bioavailability of AZD0284 will be calculated from area under the plasma concentration versus time curve (AUC) of the oral dose of AZD0284 / AUC of the IV dose of \[14C\]AZD x IV dose/Oral dose x 100
Pharmacokinetic (PK) profile of the IV dose of AZD0824 in terms of the maximum observed plasma concentration (Cmax) for \[14C\]AZD0284
Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the the time to maximum observed plasma concentration (Tmax) for \[14C\]AZD0284.
Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the area under the concentration-time curve from dosing to the last measurable concentration for \[14C\]AZD0284.
Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms the area under the concentration-time curve from dosing extrapolated to infinity for \[14C\]AZD0284.
Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the percentage of AUC(0-inf) extrapolated beyond the last measured for \[14C\]AZD0284.
Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the terminal elimination rate constant calculated from the slope of the apparent elimination phase for \[14C\]AZD0284.
Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the apparent terminal elimination half-life for \[14C\]AZD0284.
Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the terminal elimination rate constant calculated from the slope of the apparent elimination phase for \[14C\]AZD0284
Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the volume of distribution at steady state for \[14C\]AZD0284.
Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the volume of distribution at steady state for \[14C\]AZD0284.
Pharmacokinetic (PK) profile of the IV dose of AZD0284 in terms of the mean residence time for \[14C\]AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0824 in terms of the maximum observed plasma concentration (Cmax) for AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the the time to maximum observed plasma concentration (Tmax) for AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the elapsed time from dosing at which the analyte was first quantifiable in a concentration vs time profile for AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the area under the concentration-time curve from dosing to the last measurable concentration for AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms the area under the concentration-time curve from dosing extrapolated to infinity for AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the percentage of AUC(0-inf) extrapolated beyond the last measured time point for AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the terminal elimination rate constant calculated from the slope of the apparent elimination phase for AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the apparent terminal elimination half-life for AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the apparent total clearance for AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms of the apparent volume of distribution for AZD0284.
Pharmacokinetic (PK) profile of the oral dose of AZD0284 in terms the mean residence time for AZD0284.
Standard adverse event collection. An adverse event is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
The following variables will be collected after the subject has rested in the supine position for at least 5 minutes: * Systolic BP (mmHg) * Diastolic BP (mmHg) * Pulse (beats per minute \[bpm\]) * Oral body temperature
A 12-lead ECG will be obtained after the subject rested in the supine position for at least 10 minutes (using the sites own ECG machines when not performing dECGs and using the same machine as the dECGs when time points coincide).
The complete physical examinations will include an assessment of the general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
| Arm | Type | Description |
|---|---|---|
| Bioavailability of AZD0284 | EXPERIMENTAL | To assess the absolute bioavailability of a single oral dose of AZD0284 in healthy subjects. To assess the pharmacokinetics (PK) of a single intravenous (IV) microdose of \[14C\]AZD0284 in healthy subjects. |
| AZD0284 | EXPERIMENTAL | Part 1A: Following an overnight fast of at least 10 hours, each subject will receive a single dose of AZD0284 or matching placebo in the form of an oral solution with water. The total volume that the subject will receive (IMP and water) will be 240 mL. Part 1B (food cohort): Subjects, will receive a single dose of AZD0284 at a dose level in the range of or slightly above the dose level anticipated to yield therapeutic exposure, currently predicted to be achieved with 28 mg AZD0284 at twice daily dosing. The total volume that the subject will receive (IMP and water) will be 240 mL. Part 2: In Part 2, subjects will receive 1 dose level of AZD0284 (once or twice daily) with water from Day 1 to between (including) Day 7 and Day 14. The total volume that the subject will receive (IMP with water) will be 240 mL. Subjects may be dosed in either the fasted or fed state depending on emerging data from Part 1. |
| Placebo | ACTIVE_COMPARATOR | Part 1A: Following an overnight fast of at least 10 hours, each subject will receive a single dose of placebo in the form of an oral solution with water. The first cohort will receive 4.0 mg AZD0284 or placebo on Day 1. The actual dose for subsequent cohorts will be determined after review of all available safety or other pertinent data from the previous dose by the SRC Part 1B (food cohort): In Part 1B, subjects, will receive a single dose of placebo at a dose level in the range of or slightly above the dose level anticipated to yield therapeutic exposure, currently predicted to be achieved with 28 mg AZD0284 at twice daily dosing. Part 2: In Part 2, each subject will receive 1 dose level of placebo (once or twice daily) with water from Day 1 to between (including) Day 7 and Day 14. The total volume that the subject will receive (placebo with water) will be 240 mL. Subjects may be dosed in either the fasted or fed state depending on emerging data from Part 1. |
| Name | Type | Description |
|---|---|---|
| AZD0284 | DRUG | Subjects will receive a single oral dose of 4 to 120 mg AZD0284 oral suspension 5 mg/mL in the fasted state |
| [14C]AZD0284 | DRUG | Following administration of the AZD0284 oral suspension subjects will receive an IV infusion of 20 μg \[14C\]AZD0284 solution |
| Placebo | DRUG | Placebo matching AZD0284 in the form of an oral solution with water. |
Inclusion Criteria: 1. Signed and dated, written informed 2. Healthy males or non-pregnant, non-lactating healthy females. 3. Age 18 to 65 years of age. 4. Suitable veins for cannulation or repeated venepuncture. 5. Females must have a negative pregnancy test at screening and on admission to the un...