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This Phase I, randomised, single-blind, placebo-controlled study has been designed to assess the safety, tolerability, and pharmacokinetics (PK) of AZD2693 following subcutaneous (SC) administration of AZD2693 in healthy participants
The study will be performed at a single study center in Japan.
The study will comprise of following periods:
Participants will be enrolled in 4 consecutive cohorts of 11 participants where 8 participants will be randomized to receive AZD2693 and 3 participants will be randomized to receive placebo.
A participant is considered to have completed the study if the participant has completed all phases of the study including the last visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: AZD2693 | Experimental | Japanese Participants will receive Dose A of AZD2693. |
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| Cohort 2: AZD2693 | Experimental | Japanese Participants will receive Dose B of AZD2693. |
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| Cohort 3: AZD2693 | Experimental | Japanese Participants will receive Dose C of AZD2693. |
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| Cohort 4: AZD2693 | Experimental | Non-Asian Participants will receive Dose C of AZD2693 |
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| Placebo | Placebo Comparator | Japanese and Non-Asian Participants will receive placebo matching Dose A, B, and C to AZD2693. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD2693 | Drug | Participants will receive subcutaneous injection of AZD2693, once per month. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Safety and tolerability of AZD2693 compared to placebo following multiple dose SC administration in healthy participants will be evaluated. | Until Day 162 (Final/Early termination visit) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum observed plasma drug concentration (Cmax) of AZD2693 | Cmax of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Sumida-ku | 130-0004 | Japan |
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| Label | URL |
|---|---|
| Redacted CSR synopsis. | View source |
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Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at:
https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the de-identified individual patientlevel data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:
https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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The study center staff including the Investigator have to remain blinded during the clinical conduct of a given cohort with regard to study intervention (AZD2693 or placebo). The study will be blinded for all study personnel including the Investigator during the clinical conduct of the study and the Sponsor will remain blinded up to the unblinded safety review committee review of the data from the study
| Placebo | Drug | Participants will receive subcutaneous injection of placebo (volume matching to AZD2693 injection [0.9% saline solution]), once per month. |
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| Time to reach peak or maximum observed concentration following drug administration (tmax) of AZD2693 |
tmax of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized. |
| Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Terminal elimination rate constant, estimated by log-linear least-squares regression of the terminal part of the concentration-time curve (λz) of AZD2693 | λz of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Apparent terminal elimination half-life associated with the terminal slope (λz) of the semi-logarithmic concentration-time curve (t½λz) of AZD2693 | t½λz of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized. The t½λz , estimated as (ln2)/λz | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Area under the plasma concentration-time curve from time zero to 48 hours after dosing AUC (0-48) of AZD2693 | AUC(0-48) of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD2693 | AUClast of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Area under the concentration-time curve from time zero extrapolated to infinity. AUCinf is estimated by AUClast + Clast/ λz where Clast is the last observed quantifiable concentration (AUCinf) of AZD2693 | AUCinf of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD2693 | CL/F of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized. CL/F is calculated as Dose/AUCinf for single dose and for multiple dose it is calculated as Dose/AUCτAUCss. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Mean residence time (MRTinf) of AZD2693 | MRTinf of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Time delay between drug administration and the first observed concentration in plasma (tlag) of AZD2693 | tlag of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Apparent volume of distribution for parent drug at terminal phase (extravascular administration) (Vz/F) of AZD2693 | Vz/F of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized. Vz/F is estimated by dividing the apparent clearance (CL/F) by λz. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Area under the plasma concentration-time curve from time zero to time of last quantifiable analyte concentration divided by the dose administered (AUClast/D) of AZD2693 | AUClast/D of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUCinf/D) of AZD2693 | AUCinf/D of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Observed maximum plasma concentration divided by the dose administered (Cmax/D) of AZD2693 | Cmax/D of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Time of the last quantifiable concentration (tlast) of AZD2693 | tlast of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Maximum observed plasma drug concentration at steady state (Cmax) of AZD2693 | Cmax of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Minimum observed drug concentration at steady state (Cmin) of AZD2693 | Cmin of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Time to reach maximum observed plasma concentration at steady state (tmax) of AZD2693 | tmax of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Area under the concentration-time curve in the dose interval (AUCτ) of AZD2693 | AUCτ of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUCτ/D) of AZD2693 | AUCτ/D of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Accumulation ratio based on Cmax (Rac Cmax) of AZD2693 | Rac Cmax of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Accumulation ratio based on AUC (Rac AUC) of AZD2693 | Rac AUC of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Temporal change parameter in systemic exposure (TCP) of AZD2693 | TCP of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit) |
| Amount of analyte excreted into the urine from time t1 to t2 (Ae(t1-t2)) for AZD2693 | (Ae(t1-t2)) of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose) |
| Cumulative amount of analyte excreted from time zero through the last sampling interval Ae(0-last) of AZD2693 | Ae(0-last) of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose) |
| Fraction of dose excreted unchanged into the urine from time t1 to t2 fe(t1-t2) of AZD2693 | fe(t1-t2) of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose) |
| Cumulative fraction (percentage) of dose excreted unchanged into the urine from time zero to the last measured time point (fe(0-last)) of AZD2693 | fe(0-last) of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose) |
| Renal clearance of drug from plasma, estimated by dividing Ae(0-t) by AUC(0-t) where the 0-t interval is the same for both Ae and AUC (CLR) of AZD2693 | CLR of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized. | Day 1 and Day 57 (pre-dose and post-dose) |