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The purpose of this study is to examine the safety and tolerability of AZD2389 in participants with hepatic impairment and participants with normal hepatic function.
This is a single-dose, non-randomised, open-label, parallel-group study to examine the PK, fibroblast activation protein activity, safety, and tolerability of AZD2389 in participants with hepatic impairment and participants with normal hepatic function.
The study is planned to consist of:
Safety, tolerability, and available plasma PK data up to 48 hours post-dose from at least 4 participants in each of the mild hepatic impairment (CP Class A) and moderate hepatic impairment (CP Class B) cohorts must have been assessed by the investigator(s), medical monitor, and sponsor prior to the decision to proceed with evaluation/recruitment of participants with severe hepatic impairment (CP Class C). Cohort 1 (normal hepatic function) will be initiated in parallel with Cohorts 2 and 3.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Participants with normal hepatic function (sex-, age-, and body mass index [BMI]-matched) |
|
| Cohort 2 | Experimental | Participants with mild hepatic impairment (CP A classification) |
|
| Cohort 3 | Experimental | Participants with moderate hepatic impairment (CP B classification) |
|
| Cohort 4 | Experimental | Participants with severe hepatic impairment (CP C classification) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD2389 | Drug | Single oral dose of AZD2389 in participants from all cohorts |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma PK parameter Cmax | maximum observed plasma concentration | pre-dose to 48 hours post-dose |
| Plasma PK parameter AUCinf | area under the concentration-time curve from zero to infinity | pre-dose to 48 hours post-dose |
| Plasma PK parameter AUClast | area under the concentration-time curve from zero to the last measurable concentration | pre-dose to 48 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma PK parameter t1/2λz | half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve | pre-dose to 48 hours post-dose |
| Plasma PK parameter Tmax | time to reach maximum observed plasma concentration |
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Inclusion Criteria:
For Hepatic:
For Healthy:
All participants:
- Body weight ≥ 50 kg; BMI within the range of 18.0 to 42.0 kg/m2 (inclusive).
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Chandler | Arizona | 85225 | United States | ||
| Research Site |
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| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| D008103 | Liver Cirrhosis |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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Participants will be enrolled within the following groups based on their CP classification score as determined at screening: Cohort 1: Participants with normal hepatic function (sex-, age-, and body mass index [BMI]-matched)
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| pre-dose to 48 hours post-dose |
| Plasma PK parameter CL/F | apparent total body clearance of drug from plasma after extravascular administration | pre-dose to 48 hours post-dose |
| Plasma PK parameter Vz/F | apparent volume of distribution during the terminal phase after extravascular administration. | pre-dose to 48 hours post-dose |
| Urine PK parameter Ae(t1-t2) | cumulative amount of unchanged drug excreted into the urine for the interval between time 1 and time 2 | pre-dose to 48 hours post-dose |
| Urine PK parameter CLr | renal clearance of the drug from plasma | pre-dose to 48 hours post-dose |
| Urine PK parameters fe(t1-t2) | fraction of the drug excreted into the urine for the interval between time 1 and time 2 | pre-dose to 48 hours post-dose |
| Rialto |
| California |
| 92377 |
| United States |
| Research Site | Miami Lakes | Florida | 33014 | United States |
| Research Site | Orlando | Florida | 32809 | United States |
| Research Site | San Antonio | Texas | 78215 | United States |
| D008232 |
| Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |