Assess the Safety, Tolerability and Pharmacokinetics of AZD5055 Following Single and Multiple Ascending Doses in Healthy Participants
- Registration Number
- NCT05134727
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a phase I, First-in-Human study in healthy participants, performed at a single study center, consisting of 2 parts: Part 1 is a single ascending dose (SAD) study and Part 2 is a multiple ascending dose (MAD) study.
- Detailed Description
Part 1: This is a double-blind, randomized, placebo-controlled study consisting of 2 parts. Part 1: SAD and Part 2: MAD.
Part 1 will be a double-blind, randomized, placebo-controlled study, with a sequential SAD design. Three dose levels of AZD5055 are planned to be investigated in 3 cohorts. Depending on evaluation of data from the preceding cohorts, 2 additional cohorts/dose levels may be added at the discretion of the SRC.
Part 1 will comprise of:
* A Screening Period of a maximum of 6 weeks.
* A Treatment Period during which subjects will be resident at the Clinical Unit from 1 day before IMP administration (Day 1) until at least 72 hours after IMP administration (Day 4). Subjects will receive a single oral dose of AZD5055 or placebo on Day 1.
* A Follow up Visit within 6 ± 1 day after the IMP dose.
Part 2 will be a double-blind, randomized, placebo-controlled study with a MAD design. Subjects will receive AZD5055 on Day 1 and Day 3 to Day 16, with no dosing on Day 2. Subjects will be naïve, ie, will not have participated in Part 1 of this study. Three dose levels of AZD5055 are planned to be investigated in 3 cohorts. Depending on evaluation of data of the preceding cohorts, up to 2 additional dose levels/cohorts may be added or expanded at the discretion of the SRC.
Part 2 will comprise of:
* A Screening Period of a maximum of 6 weeks.
* A treatment period with a dosing frequency (QD or BID) that will be dependent on emerging PK data from Part 1:
A) For cohorts with QD dosing regimens:
• A Treatment Period during which subjects will be resident at the Clinical Unit from 1 day before IMP administration (Day -1) until at least 72 hours after the last dose given on Day 16 (Day 19). Subjects will be dosed for a total of 15 days, receiving a single QD morning dose of AZD5055 or placebo on Day 1 and on Days 3 through Day 16.
B) For cohorts with BID dosing regimens:
* A Treatment Period during which subjects will be resident at the Clinical Unit from 1 day before IMP administration (Day -1) until at least 72 hours after the last dose given on Day 16 (Day 19). Subjects will be dosed for a total of 15 days, receiving a single morning dose of AZD5055 or placebo on Day 1 and Day 16, and repeated BID dosing on Day 3 through Day 15, 12 hours (± 30 minutes) apart.
* A Follow-up Visit within 6 ± 1 day after the last IMP dose, and an additional Follow up Visit within 29 ± 2 days after the last IMP dose.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2 (multiple ascending doses [MAD]) AZD5055 Healthy participants will be randomized to repeated dosing with AZD5055 or placebo Part 2 (multiple ascending doses [MAD]) Placebo Healthy participants will be randomized to repeated dosing with AZD5055 or placebo Part 1 (single ascending doses [SAD]) Placebo Healthy participants will be randomized to a single dose of AZD5055 or placebo. Part 1 (single ascending doses [SAD]) AZD5055 Healthy participants will be randomized to a single dose of AZD5055 or placebo.
- Primary Outcome Measures
Name Time Method Part 2: Number of participants with AEs Until follow-up (45 days post-last dose) (approximately up to 89 days) To investigate the safety and tolerability of AZD5055 by assessment of AEs (non-serious and serious) following administration of MAD
Part 1: Number of participants with adverse events (AEs) Until Follow-up (7 days post dose) (approximately up to 53 days) To investigate the safety and tolerability of AZD5055 by assessment of AEs (non-serious and serious) following administration of SAD
- Secondary Outcome Measures
Name Time Method Part 1: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 2: Maximum observed plasma (peak) drug concentration (Cmax) Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 1: Time to reach maximum observed concentration (tmax) Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 1: Maximum observed plasma (peak) drug concentration (Cmax) Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 1: Area under plasma concentration time curve from zero to infinity (AUCinf) Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 2: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 1: Partial area under the plasma concentration-time curve from 0 to time 24 hours post dose [AUC(0-24)] Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 2: Area under plasma concentration time curve from zero to infinity (AUCinf) Day 1: profile 0-48 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 2: Time to reach maximum observed concentration (tmax) Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 1: Mean residence time of the unchanged drug in the systemic circulation (MRTinf) Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 2: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 1: Apparent volume of distribution following extravascular administration based on terminal phase (Vz/F) Day 1: profile 0-72 hours after dose. To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 1: Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)] Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 1: Cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)] Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 2: Accumulation ratio (Rac) Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 2: Partial area under the plasma concentration-time curve from 0 to time 12 hours post dose [AUC(0-12)] Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 2: Area under plasma concentration-time curve in the dose interval (repeat dose only) (AUC[0-1τ]) Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 2: Half-life associated with terminal slope (λz) of a semi logarithmic concentration-time curve (t½λz) Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 2: Apparent volume of distribution following extravascular administration based on terminal phase (Vz/F) Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 1: Partial area under the plasma concentration-time curve from 0 to time 12 hours post dose [AUC(0-12)] Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 1: Half-life associated with terminal slope (λz) of a semi logarithmic concentration-time curve (t½λz) Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 1: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 2: Partial area under the plasma concentration-time curve from 0 to time 24 hours post dose [AUC(0-24)] Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 2: Mean residence time of the unchanged drug in the systemic circulation (MRTinf) Day 1: profile 0-48 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 2: Cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)] Day 1-3 and Day 16-19 To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 1: Renal clearance of drug from plasma (CLR) Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 2: Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)] Day 1-3 and Day 16-19 To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 2: Renal clearance of drug from plasma (CLR) Day 1-3 and Day 16-19 To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 2: Temporal change parameter in systemic exposure (TCP) Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of MAD to healthy participants
Part 1: Accumulation ratio (Rac) Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Part 1: Temporal change parameter in systemic exposure (TCP) Day 1: profile 0-72 hours after dose To characterize the PK of AZD5055 following oral administration of SAD to healthy participants
Trial Locations
- Locations (1)
Research Site
🇺🇸Brooklyn, Maryland, United States