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.
Phase 1
Not yet recruiting
- Conditions
- Healthy Participants
- Interventions
- Drug: balcinrenone/ dapagliflozin
- Registration Number
- NCT06979388
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 14
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 any clinically significant abnormalities on 12-lead ECG 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment ABC balcinrenone/ dapagliflozin Participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule on Day 1 and then followed by a washout period of 72 hours. On Day 4, participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food, followed by a washout period of 72 hours. On Day 7, participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively). Treatment ABC quinidine Participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule on Day 1 and then followed by a washout period of 72 hours. On Day 4, participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food, followed by a washout period of 72 hours. On Day 7, participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively). Treatment ACB balcinrenone/ dapagliflozin The participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule on Day 1 and then followed by washout period of 72 hours. On Day 4, participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively), followed by a washout period of 72 hours. On Day 7, participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food. Treatment ACB quinidine The participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule on Day 1 and then followed by washout period of 72 hours. On Day 4, participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively), followed by a washout period of 72 hours. On Day 7, participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food. Treatment BCA balcinrenone/ dapagliflozin The participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food on Day 1 and then followed by washout period of 72 hours. On Day 4, participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively), followed by a washout period of 72 hours. On Day 7, participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule. Treatment BCA quinidine The participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food on Day 1 and then followed by washout period of 72 hours. On Day 4, participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively), followed by a washout period of 72 hours. On Day 7, participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule. Treatment BAC balcinrenone/ dapagliflozin The participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food on Day 1 and then followed by washout period of 72 hours. On Day 4, participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule and then followed by washout period of 72 hours. On Day 7 participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively). Treatment BAC quinidine The participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food on Day 1 and then followed by washout period of 72 hours. On Day 4, participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule and then followed by washout period of 72 hours. On Day 7 participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively). Treatment CAB balcinrenone/ dapagliflozin The participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively), followed by a washout period of 72 hours. On Day 4, participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule and then followed by washout period of 72 hours. On Day 7, participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food. Treatment CAB quinidine The participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively), followed by a washout period of 72 hours. On Day 4, participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule and then followed by washout period of 72 hours. On Day 7, participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food. Treatment CBA balcinrenone/ dapagliflozin The participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively), followed by a washout period of 72 hours. On Day 4, participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food, followed by a washout period of 72 hours. On Day 7, participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule. Treatment CBA quinidine The participants will receive Treatment C (quinidine, fasted), balcinrenone/dapagliflozin capsule dosed together with a P-gp inhibitor tablets (2 doses of quinidine separated by 4 hours, 1 hour prior and 3 hours post balcinrenone/dapagliflozin administration, respectively), followed by a washout period of 72 hours. On Day 4, participants will receive Treatment B (fed), balcinrenone/dapagliflozin capsule dosed together with food, followed by a washout period of 72 hours. On Day 7, participants will receive Treatment A (reference, fasted), balcinrenone/dapagliflozin capsule.
- Primary Outcome Measures
Name Time Method Time to reach maximum observed concentration (tmax) From Day 1 to Day 10 Apparent volume of distribution based on the terminal phase (Vz/F) From Day 1 to Day 10 Apparent total body clearance (CL/F) From Day 1 to Day 10 Renal Clearance (CLR) (balcinrenone only) From Day 1 to Day 10 Drug concentration in plasma at 24 hours post-dose (C24) From Day 1 to Day 10 Area under concentration-time curve from time zero to infinity (AUCinf) From Day 1 to Day 10 Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) From Day 1 to Day 10 Maximum observed drug concentration (Cmax) From Day 1 to Day 10 Terminal elimination half-life (t1/2λz) From Day 1 to Day 10
- Secondary Outcome Measures
Name Time Method Number of participants with adverse events (AEs) and serious adverse events (SAEs) From Screening (Day -28 to Day -2) until Follow-up (Day 12 to Day 14)
Trial Locations
- Locations (1)
Research Site
🇬🇧Harrow, United Kingdom