A Phase I, Multicentre, Single-Dose, Non-Randomised, Open-Label, Parallel-Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD9550 and AZD6234
Summary
The purpose of this study is to examine the safety and tolerability of AZD6234 and AZD9550 in participants with hepatic impairment and participants with normal hepatic function.
Detailed description
This Phase I, open-label, parallel group study will investigate the single SC dose PK, safety, tolerability, and immunogenicity of separate administrations of AZD9550 and AZD6234 to male and female participants with severe and moderate hepatic impairment compared to matched controls with normal hepatic function. To minimize any potential impact from AZD9550 administered in Period 1, AZD6234 will be administered in Period 2 following a washout period. Results from separate injections will ultimately inform the single dose PK, safety, and tolerability of AZD9550 and AZD6234 administered. Approximately 56 participants will be screened to achieve a total of 16 planned for study intervention (8 per group for CP Class C and CP Class B) with 6 evaluable participants in each of the 2 impairment groups (severe and moderate), and up to 12 participants with normal hepatic function. Initially 8 participants with normal hepatic function will be recruited, matched on a group level regarding sex, age, and BMI to the participants with hepatic impairment. Additional participants with normal hepatic function, up to a total of 12, may be included if needed to meet the matching criteria. Child-Pugh scoring 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 by a local laboratory at screening: Group 1: Participants with severe hepatic impairment (CP Class C, score of 10 to 15). Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9). Group 3: Participants with normal hepatic function matched on a group level regarding sex, age, and BMI to the participants with hepatic impairment.
Arms & interventions
- DrugAZD6234
Single subcutaneous dose of AZD6234 in participants from all groups
- DrugAZD9550
Single subcutaneous dose of AZD9550 in participants from all groups
Outcome measures
Primary
PK parameters AUCinf
To compare the plasma PK of separate single SC doses of AZD9550 and AZD6234 in participants with severe and moderate hepatic impairment with matched controls with normal hepatic function
Time frame: Day 0 through Day 56
PK parameters AUClast
To compare the plasma PK of separate single SC doses of AZD9550 and AZD6234 in participants with severe and moderate hepatic impairment with matched controls with normal hepatic function
Time frame: Day 0 through Day 56
PK parameters Cmax
To compare the plasma PK of separate single SC doses of AZD9550 and AZD6234 in participants with severe and moderate hepatic impairment with matched controls with normal hepatic function
Time frame: Day 0 through Day 56
Secondary
PK parameters tmax
Time frame: Day 0 through Day 56
Prevalence and incidence of ADAs to AZD9550 and AZD6234
Time frame: Day 0 through Day 56
PK parameters t1/2λz
Time frame: Day 0 through Day 56
PK parameters CL/F
Time frame: Day 0 through Day 56
PK parameters Vz/F
Time frame: Day 0 through Day 56
Eligibility criteria
Study locations (4)
Research Site
Chandler, Arizona, 85225
Research Site
Rialto, California, 92377
Research Site
Miami Lakes, Florida, 33014
Research Site
San Antonio, Texas, 78215