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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02303574 | Single + Multiple Ascending Dose and Food Effect Study of AZD7986 in Healthy Volunteers, PK, PD and Safety Study | PHASE1 | COMPLETED | 89 | — | — | Dec 3, 2014 | Aug 3, 2016 | Dec 11, 2018 | 1 | United Kingdom |
To investigate the safety and tolerability of AZD7986 by assessment of AEs (non-serious and serious) following administration of oral solution in SAD (Part 1a - fasted state and 1b - fed state) and MAD (Part 2)
To assess the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable analyte concentration (AUC(0-last)) for Part 1a (fasted state) and 1b (fed state) - SAD
To assess the area under the plasma concentration versus time curve, from time zero to the time of the last quantifiable analyte concentration (AUC(0-last)) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2
To assess the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) for Part 1a (fasted state) and 1b (fed state) - SAD. AUC was estimated by AUC(0 last) + Clast/λz where Clast was the last observed quantifiable concentration.
To assess the area under plasma concentration-time curve from zero extrapolated to infinity (AUC) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2. Note: Day 1 data calculated over a 24 hour period and was therefore not comparable with the Day 21 and Day 28 data
To assess area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCτ) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2. AUCτ: AUC from time zero to 24 hours post-dose presented on Day1
To assess the observed maximum plasma concentration (Cmax) for Part 1a (fasted state) and 1b (fed state) - SAD. Cmax was taken directly from the individual concentration-time curve
To assessthe observed maximum plasma concentration (Cmax) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2. Cmax was taken directly from the individual concentration-time curve
To assess the time to reach maximum observed concentration (tmax) for Part 1a (fasted state) and 1b (fed state) - SAD; tmax was taken directly from the individual concentration-time curve
To assess the time to reach maximum observed concentration (tmax) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; tmax was taken directly from the individual concentration-time curve
To assess the half life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½.λz) for Part 1a (fasted state) and 1b (fed state) - SAD
To assess the apparent terminal elimination half-life (t½.λz) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; tmax was taken directly from the individual concentration-time curve. Note: Day 1 data were calculated over a 24 hour period and was therefore not comparable with the Day 21 and Day 28 data
To assess the mean residence time (MRT) for Part 1a (fasted state) and 1b (fed state) - SAD
To assess the mean residence time (MRT) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2
To assess the apparent clearance (CL/F) for Part 1a (fasted state) and 1b (fed state) - SAD; CL/F for parent drug was estimated as dose divided by AUC
To assess the apparent clearance (CL/F) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; CL/F for parent drug was estimated as dose divided by AUC
To assess the apparent volume of distribution (Vz/F) for Part 1a (fasted state) and 1b (fed state) - SAD; Vz/F at terminal phase (extravascular administration) was estimated by dividing the apparent clearance (CL/F) by λz
To assess the the apparent volume of distribution (Vz/F) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; Vz/F at terminal phase (extravascular administration) was estimated by dividing the apparent clearance (CL/F) by λz
To assess the accumulation ratio for (Rac(AUC(0-τ)) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; estimated as AUC(0-τ) Day 21/AUC(0-24) Day 1
To assess the accumulation ratio for Cmax (Rac(Cmax)) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; estimated as Cmax Day 21/Cmax Day 1
To assess the temporal change parameter (TCP) following a single AZD7986 dose on Day 1 and daily dosing on Days 21 or 28 at 10, 25 and 40 mg in Part 2; estimated as AUC(0-τ) Day 21/AUC Day 1, if extrapolated part was less than 20%
To assess cumulative amount of analyte excreted from 0 to 48 hours (CumAe0-48) after single dose administration of AZD7986 oral solution in Part 1a (fasted state) and 1b (fed state)
To assess percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0-48) after single dose administration of AZD7986 oral solution in Part 1a (fasted state) and 1b (fed state)
To assess renal clearance from 0 to 48 hours (CLR0-48) after single dose administration of AZD7986 oral solution in Part 1a (fasted state) and 1b (fed state)
To assess cumulative amount of analyte excreted from 0 to 24 hours (CumAe0-24) for Part 2
To assess percentage of dose excreted unchanged into the urine from 0 to 24 hours (Cumfe0 24) for Part 2
To assess renal clearance from 0 to 24 hours (CLR0-24) for Part 2
To assess Cumulative amount of analyte excreted from 0 to 48 hours (CumAe0-48)) for Part 2
To assess Percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0 48) for Part 2
To assess Percentage of dose excreted unchanged into the urine from 0 to 48 hours (Cumfe0 48) for Part 2
| Arm | Type | Description |
|---|---|---|
| AZD7986, single and mulltiple doses | EXPERIMENTAL | In Part 1 up to 8 cohorts with single doses starting with 5 mg AZD7986 as oral solution. In Part 2 up to 5 cohorts with multiple doses of AZD7986 as oral solution |
| Placebo, single and multiple doses | PLACEBO_COMPARATOR | In Part 1 up to 8 cohorts and in Part 2 up to 5 cohorts with matching placebo to AZD7986 as oral solution |
| Name | Type | Description |
|---|---|---|
| AZD7986, oral solution, 1 to 50 mg/mL | DRUG | Starting dose in single ascending dose part: 5 mg |
| Placebo, oral solution | DRUG | Matching placebo |
Inclusion Criteria: 1. Provision of signed and dated written informed consent prior to any study specific procedures. 2. Healthy male or female subjects aged 18 to 50 years (inclusive) at screening with suitable veins for cannulation or repeated venepuncture. 3. Females must be of non-child-bearing...