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Completed

NCT Number: NCT06357520

A Study to Investigate the Pharmacokinetics of Baxdrostat When Given Alone and in Combination With Itraconazole in Healthy Participants

The main purpose of this study is to assess the effect of itraconazole on the pharmacokinetic (PK) of baxdrostat.

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Key information

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research Site

Brooklyn, Maryland, 21225, United States

About this study

This study will be an open-label, 3-period fixed sequence study conducted at a single Clinical Unit.

The study will comprise of:

  • A Screening Period of maximum 28 days
  • Period 1: Period 1 will start from Day -1 to Day 6 (followed by pharmacokinetic (PK) sampling of baxdrostat). Baxdrostat administration on Day 1 to Day 6
  • Period 2: Period 2 will start from Day 6 (after the last PK sample in period 1) to Day 8. Itraconazole administration on Days 6 to 8 (twice a day [BID] on Day 6 and once daily [QD] on Days 7 and 8)
  • Period 3: Period 3 will start from Day 9 to Day 17. Baxdrostat administration on Day 9 and itraconazole administration on Days 9 to 16 QD
  • A Final Follow-up Visit at 7 to 14 days after the last baxdrostat PK sample in Period 3

All participants will receive 2 single doses of baxdrostat and 12 doses of itraconazole, under fed conditions.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy male and/or female participants of non-childbearing potential aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
  • All female participants must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit (Study Day -1).
  • Have a body mass index between 18 and 32 kilograms per meter square (kg/m2) inclusive and weigh greater than or equal to (>=) 50 kilograms (kg) and less than or equal to <=) 120 kg.

Exclusion criteria

  • History of any clinically important disease or disorder which, in the opinion of the principal investigator (PI), 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.
  • History of drug-related hepatic toxicity.
  • Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
  • History of any treatment with QT prolongation drugs.
  • History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to baxdrostat or itraconazole.
  • Participants who have previously received baxdrostat.

Treatment and study plan

baxdrostat

Drug

Baxdrostat tablet will be administered orally.

Other names: CIN-107

Itraconazole

Drug

Itraconazole capsule will be administered orally.

Primary outcomes

  1. Area Under Plasma Concentration-Time Curve From Time Zero To Infinity (AUCinf)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The effect of itraconazole on the PK (AUCinf) of baxdrostat will be assessed.

  2. Maximum Observed Plasma Drug Concentration (Cmax)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The effect of itraconazole on the PK (Cmax) of baxdrostat will be assessed.

Secondary outcomes

  1. Extrapolated Area Under The Curve From Tlast to Infinity (AUCextr)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (AUCextr) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  2. Area Under Plasma Concentration Curve from Time Zero to the Last Quantifiable Concentration (AUClast)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (AUClast) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  3. Apparent Total Body Clearance (CL/F)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (CL/F) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  4. Apparent Volume Of Distribution Based On The Terminal Phase (Vz/F)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (Vz/F) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  5. Terminal Elimination Half-life (t1/2λz)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (t1/2λz) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  6. Terminal Rate Constant (λz)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (λz) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  7. Mean Residence Time (MRTinf)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (MRTinf) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  8. Time To Reach Maximum Observed Concentration (tmax)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (tmax) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  9. Ratio of Baxdrostat (Baxdrostat + Itraconazole) to Baxdrostat (Alone) Based on Maximum Plasma Concentration (RCmax)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (RCmax) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  10. Ratio of Baxdrostat (Baxdrostat + Itraconazole) to Baxdrostat (Alone) Based on AUClast (RAUClast)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (RAUClast) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  11. Ratio of Baxdrostat (Baxdrostat + Itraconazole) to Baxdrostat (Alone) Based on AUCinf (RAUCinf)

    Time frame: Period 1: Days 1 to 6 (pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours post-dose); Period 3: Days 9 to 17 (pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours)

    The PK (RAUCinf) of baxdrostat when baxdrostat is administered alone or in combination with itraconazole will be evaluated.

  12. Number of Participants with Adverse Events

    Time frame: Up to 8 weeks

    The safety and tolerability of baxdrostat alone and in combination with itraconazole will be assessed.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

An Open-label, Fixed Sequence Study in Healthy Participants to Assess the Pharmacokinetics of Baxdrostat When Administered Alone and in Combination With Itraconazole

Important dates

Study start
2024
Primary completion
2024
Study completion
2024
First posted
Apr 10, 2024
Registry last updated
Jul 3, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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