A Phase I Study to Investigate the Effect of Hepatic Impairment on the PK, Safety, and Tolerability of AZD2693

Study Overview
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Brief Summary
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Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment

Detailed Description
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This is a Phase I, multicentre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD2693 administered as an subcutaneous injection in male and female participants with mild, moderate, or severe hepatic impairment compared with male and female participants with normal hepatic function (as control). Eight participants with mild impairment (CP Class A); 8 participants with moderate impairment (CP Class B); 8 participants with severe impairment (CP Class C); and 8 to12 participants with normal hepatic function matched on a group level regarding age, body weight, and sex to the impaired participants are planned for study intervention with the goal of having at least 6 evaluable participants within each group. Study participants who self-withdraw after study intervention may be replaced to ensure that at least 6 participants per group are evaluable and complete the study per protocol. An evaluable participant is defined as having adequate plasma PK profile to meet the primary study objective. Child-Pugh scoring, detailed in Table 2, will be used to determine the level of hepatic impairment. Participants will be enrolled into the following groups based on their CP classification score as determined at screening: Group 1: Participants with mild hepatic impairment (CP Class A, score of 5 or 6). Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9). Group 3: Participants with severe hepatic impairment (CP Class C, score of 10 to 15). Group 4: Participants with normal hepatic function Study Arms and Duration: Planned screening duration per participant: up to 4 weeks. Planned study duration (screening to follow-up) per participant: up to 16 weeks.

Official Title
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A Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of AZD2693

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: AZD2693


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Hepatic: Participant with a diagnosis of chronic and stable hepatic impairment For Healthy: Participant with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or 12-lead ECGs, All participants: - Body weight ≥ 50 kg; BMI within the range of 18.0 to 40.0 kg/m2 (inclusive) as measured at screening Exclusion Criteria: Participant with impaired hepatic function has eGFR < 60 mL/minute/1.73 m2 and participant with normal hepatic function has eGFR < 90 mL/minute/1.73 m2 Positive test for HIV at screening History or presence of clinically significant thyroid disease History or presence of clinically significant or unstable medical or psychiatric condition History of any major surgical procedure within 30 days prior to study intervention

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be enrolled within the following groups based on their CP classification score as determined at screening: Group 1: Participants with mild hepatic impairment (CP Class A, score of 5 or 6). Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9). Group 3: Participants with severe hepatic impairment (CP Class C, score of 10 to 15). Group 4: Participants with normal hepatic function matched on a group level regarding age, body weight, and sex to the impaired groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Participants with mild hepatic impairment (CP Class A, score of 5 or 6) | Drug: AZD2693<br>* Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment<br>|
| Experimental: Group 2<br>Participants with moderate hepatic impairment (CP Class B, score of 7 to 9) | Drug: AZD2693<br>* Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment<br>|
| Experimental: Group 3<br>Participants with severe hepatic impairment (CP Class C, score of 10 to 15) | Drug: AZD2693<br>* Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment<br>|
| Experimental: Group 4<br>Participants with normal hepatic function matched on a group level regarding age, body weight, and sex to the impaired groups | Drug: AZD2693<br>* Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters AUCinf | area under the concentration-time curve (AUC) from zero to infinity (AUCinf) | 85 days | 
| PK parameters AUClast | area under the concentration-time curve from time zero to last time of quantifiable concentration | 85 days | 
| PK parameters Cmax | maximum observed plasma concentration | 85 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters tmax | tmax: time to maximum observed plasma concentration | 85 days | 
| PK parameters tlast | tlast: time of the last measurable concentration | 85 days | 
| PK parameters t1/2λz | apparent terminal elimination half-life | 85 days | 
| PK parameters CL/F | CL/F: apparent clearance | 85 days | 
| PK Parameters Vz/F | Vz/F: apparent volume of distribution based on terminal phase | 85 days | 
| PK parameters CLR | CLR: Renal clearance of drug from plasma | 85 days | 
| PK parameters fe | fe: Percentage of dose excreted unchanged in urine | 85 days | 
| PK parameters Ae | Amount of unchanged drug excreted into urine | 85 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild, Moderate, Severe, Healthy Matches