Clinical trial NCT06979388: A Study to Investigate the Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics in Fed and Fasted State and Pharmacokinetics of Balcinrenone When Dosed With a P-gp Inhibitor in Healthy Participants.
Official title: A Phase I, Randomised, Single-dose, Open-label, 3-period, 3-treatment, 3-way Crossover Study to Assess the Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics in Fed and Fasted State and Pharmacokinetics of Balcinrenone When Dosed With a P-gp Inhibitor in Healthy Participants.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Food effect
Mineralocorticoid receptor modulator
P-glycoprotein inhibitor
Fed and fasted state
Standardised high-fat and high-calorie meal
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2025-05-19
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to assess the effect of food on balcinrenone/ dapagliflozin pharmacokinetics in fed and fasted state and pharmacokinetics of balcinrenone when dosed with a P-gp inhibitor in healthy participants.

Detailed description: This study will be an open-label, randomised, 3-period, 3-treatment, single-dose, 3-way crossover study in healthy participants (males and females), performed at a single study site.

The study comprises of:

* Screening period of 4 weeks within the interval of Day -28 and Day -2.
* Three treatment periods during which participants will be residing at the Clinical Unit from the day before the first study intervention administration (Day -1). The participant will be discharged on Day 10.

  * Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule dosed in the fasted state.
  * Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food.
  * Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule (dosed together with a P-gp inhibitor tablets (quinidine) in fasted state.

Participants will be randomised on Day 1 to one of the following 6 treatment sequences: ABC, ACB, BCA, BAC, CAB, or CBA. Each participant will receive all 3 treatments (A, B, and C) in the sequence participant was randomised to. Each treatment will be separated by a washout period of 72 hours; thus, each participant will receive study intervention on Day 1, Day 4, and Day 7.

• A final Follow-up Call within 5 - 7 days (Day 12-14) after the last study intervention administration.

Eligibility criteria: Main Inclusion Criteria:

* Have a Body Mass Index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
* All females of childbearing potential must have a negative pregnancy test.
* Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception.

Main Exclusion Criteria:

* History of any clinically important disease or disorder which may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study
* History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
* Any clinically important illness, medical/major surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
* Any clinically important abnormalities in clinical chemistry, haematology, urinalysis or vital signs.
* Positive result for serum hepatitis B surface antigen, hepatitis C antibody, and HIV antibody
* History of long QT syndrome or history of additional risk factors for QT prolongation - for example a family history of long QT syndrome or the use of concomitant medications known to prolong the QT/QTc interval. Any clinically significant abnormalities on 12-lead ECG at the Screening Visit, as judged by the investigator, including but not limited to any significant arrythmia, conduction abnormalities, and/or prolonged QTcF \> 450 ms.
* Current smokers or those who have smoked or used nicotine products within the previous 3 months prior to Screening Visit.
* History of alcohol or drug abuse. Positive screen for drugs of abuse, alcohol or cotinine.
* History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
* History of hypersensitivity to drugs with a similar chemical structure or class to balcinrenone, dapagliflozin and quinidine. Any contraindications listed for dapagliflozin and quinidine.
* Use of drugs with enzyme inducing properties within 3 weeks prior to the first administration of study intervention.
* Use of any prescribed or nonprescribed medication, herbal remedies or intake of \> 3 × daily recommended levels of vitamins and minerals during the 2 weeks prior to the first administration of study intervention
* Plasma donation within one month of screening or any blood donation/blood loss \> 500 mL during the 3 months prior to screening.

Primary outcomes:
measure: Area under concentration-time curve from time zero to infinity (AUCinf)
timeFrame: From Day 1 to Day 10
measure: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: From Day 1 to Day 10
measure: Maximum observed drug concentration (Cmax)
timeFrame: From Day 1 to Day 10
measure: Terminal elimination half-life (t1/2λz)
timeFrame: From Day 1 to Day 10
measure: Time to reach maximum observed concentration (tmax)
timeFrame: From Day 1 to Day 10
measure: Apparent volume of distribution based on the terminal phase (Vz/F)
timeFrame: From Day 1 to Day 10
measure: Apparent total body clearance (CL/F)
timeFrame: From Day 1 to Day 10
measure: Renal Clearance (CLR) (balcinrenone only)
timeFrame: From Day 1 to Day 10
measure: Drug concentration in plasma at 24 hours post-dose (C24)
timeFrame: From Day 1 to Day 10
Secondary outcomes:
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From Screening (Day -28 to Day -2) until Follow-up (Day 12 to Day 14)
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Research Site
Study officials:
References: