Kidney Failure
Conditions
Brief summary
The purpose of this study is to investigate the effect of HD on single oral dose PK, safety, and tolerability of balcinrenone/dapagliflozin to male and female participants with kidney failure on intermittent HD.
Interventions
Participants will be receiving balcinrenone/ dapagliflozin before or after hemodialysis
Sponsors
AstraZeneca
Fortrea
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
There will be two treatment periods performed in a crossover fashion in order to evaluate the PK of 40 mg/10 mg balcinrenone/dapagliflozin with dosing before and after HD, with a 7-day washout period between the two treatments.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participant must have kidney failure and must have been on stable intermittent HD for at least 3 months prior to screening. * Participant must be stable on a concomitant medication and/or treatment regimen (defined as not starting a new treatment/medication\[s\] or a change in the dosage or frequency of the concomitant medication\[s\] within at least 4 weeks prior to screening). * Participants with controlled T2DM may be included, if they have: (a) HbA1c ≤ 10% at screening. * Body weight ≥ 50 kg and BMI within the range 18 to 40 kg/m2, inclusive, as measured at screening. * All female participants must have a negative serum pregnancy test at screening and all females of child-bearing potential must have a negative serum pregnancy test on Periods 1 and 2 Day -1 and must not be lactating (confirmed at screening). Females must also fulfil one of the following criteria: Females not of child-bearing potential, defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation) or who are post-menopausal; OR Females of child-bearing potential who are sexually active with a nonsterilised male must use one highly effective method of birth control from enrolment throughout the study and until at least 4 weeks after the last dose of study intervention * Capable of giving signed informed consent * Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research that supports the Genomic Initiative
Exclusion criteria
* Presence of any uncontrolled or clinically significant disease or disorder (other than renal disease and conditions related to the renal disease, such as stable T2DM and stable hypertension), or any medical or surgical condition that, in the opinion of the investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk (according to the investigator's judgement) if he/she participates in the clinical study. * Any clinically significant illness, medical/major surgical procedure, or trauma within 4 weeks prior to the first study intervention * Severe hepatic impairment (CP Class C). * History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to balcinrenone and dapagliflozin * Abnormal resting vital signs at screening or Period 1 Day -1 (after resting for at least 5 minutes) of: (a) supine BP: (i) \> 180 mmHg or \< 90 mmHg systolic. (ii) \> 95 mmHg or \< 40 mmHg diastolic. * Successful renal transplant patients, participants waiting for organ transplant scheduled to occur during the study, and those with a history of acute kidney injury occurring within 3 months prior to screening. Nonfunctioning renal allografts are allowed * Any clinically significant abnormalities on 12-lead ECG at the screening, as judged by the investigator * Positive test for human immunodeficiency virus at screening. * Positive results at screening for hepatitis B surface antigen or hepatitis C antibody. * Known history of drug or alcohol abuse within 1 year of screening and/or consumes \> 14 units per week for males and \> 7 units per week for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine * The following medications are prohibited within 4 weeks prior to the first study intervention until follow-up: (a) MR antagonists; (b) SGLT2 inhibitors * The following medications are prohibited within 1 week prior to the first study intervention until follow-up: Strong or moderate inducers or inhibitors of CYP3A4 * Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days prior to study intervention in this study or, if known, 5 half-lives from last dose in the previous study to study intervention in this study, whichever is longest * Previous enrolment in the present study. * Positive screen for drugs of abuse including cannabis/marijuana and/or alcohol test at screening or Period 1 Day -1. * Receipt of blood products within 2 months prior to Period 1 Day -1, plasma or platelets donation within 1 month prior to Period 1 Day -1, or any blood donation/blood loss \> 500 mL within 3 months prior to Period 1 Day -1. * History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to Period 1 Day -1. * Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) as judged by the investigator * Involvement of any AstraZeneca or clinical unit employee or their close relatives. * Vulnerable participants, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order. * Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. Inability to eat at least 80% of the breakfast meal on Periods 1 and 2 Day 1 is exclusionary.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters AUCinf | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the effect of HD on the PK of balcinrenone/dapagliflozin |
| PK Parameters AUClast | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the effect of HD on the PK of balcinrenone/dapagliflozin |
| PK Parameters Cmax | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the effect of HD on the PK of balcinrenone/dapagliflozin |
| PK parameters C24 from plasma | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD |
| PK parameters tmax from plasma | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD |
| PK parameters t1/2λz from plasma | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD |
| PK parameters CLNR (balcinrenone only) from plasma | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD |
| PK parameters CL/F from plasma | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD |
| PK parameters AUC(t1-t2)_out from plasma | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD |
| PK parameters CLD from dialysate | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in dialysate in participants with kidney failure on HD |
| PK parameters AeD from dialysate | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in dialysate in participants with kidney failure on HD |
| PK parameters feD from dialysate | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in dialysate in participants with kidney failure on HD |
| PK parameters Vz/F from plasma | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD |
| PK parameters AUC(t1-t2) from plasma | Day 1 to 3 for each treatment period (each treatment period is 4 days) | To evaluate the PK of balcinrenone/dapagliflozin in plasma in participants with kidney failure on HD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AEs | from Period 1, Day 1 until follow-up on Day 9-11 post-dose Period 2. | To assess the safety and tolerability of single doses of balcinrenone/dapagliflozin in participants with kidney failure on HD |
| SAEs | from screening until follow-up on Day 9-11 post-dose Period 2 | To assess the safety and tolerability of single doses of balcinrenone/dapagliflozin in participants with kidney failure on HD |
Countries
United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed