A Study to Assess the Effect of AZD5462 on the Pharmacokinetics of Midazolam, Rosuvastatin and Digoxin
Condition: Healthy Participants
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will assess the effect of multiple doses of AZD5462 on the PK of oral midazolam
      (CYP3A4 probe), rosuvastatin (OATP1B1/3, BCRP probe), and digoxin (P-gp probe) in healthy
      participants.

      This study will consist of 2 treatment arms (Treatment Arms A and B) and within each
      treatment arm, the participants will first be administered the probe substrates (midazolam,
      rosuvastatin, and digoxin) alone followed by administration of the probe substrates together
      with AZD5462. The treatment arms differ in the dose of AZD5462 being administered and will be
      performed sequentially starting with Treatment Arm A (AZD5462 Dose A, high dose treatment
      arm) and followed by Treatment Arm B (AZD5462 Dose B, low dose treatment arm). Each treatment
      arm will include 5 periods.

      Thirty two participants in total (16 participants per treatment arm) will be enrolled to
      ensure at least 24 evaluable participants (12 participants per treatment arm) at the end of
      the last treatment period.

      A follow-up visit at Day 24 (+-1 Day) will be conducted via a phone call.
    

Detailed description: 
      This is a phase I, single-centre, 2-treatment arm, 5-period, fixed sequence study.

      The Study Will Comprise of a Screening Period and Five Treatment Periods:

        -  Screening Period (Maximum 28 Days) Participant eligibility will be confirmed during the
           Screening Visit.

        -  Period 1 (Day 1) Single dose administration of midazolam on Day 1.

        -  Period 2 (Day 2) Single dose administration of rosuvastatin and digoxin on Day 2. There
           will be a minimum washout period of 3 days between Period 2 and Period 3.

        -  Period 3 (Days 6 to 14) Single dose administration of rosuvastatin and digoxin together
           with AZD5462 (Treatment Arm A, Dose A; Treatment Arm B, Dose B) on Day 6. AZD5462 will
           continue to be administered throughout the period including Day 14.

        -  Period 4 (Day 15) Single dose administration of midazolam together with AZD5462
           (Treatment Arm A, Dose A; Treatment Arm B, Dose B) at steady state on Day 15.

        -  Period 5 (Days 16 to 18) Single dose administration of rosuvastatin and digoxin together
           with AZD5462 (Treatment Arm A, Dose A; Treatment Arm B, Dose B) at steady state on Day
           16. AZD5462 will continue to be administered on Days 17 and 18.

      Participants will be resident in the study centre when dosed with probe substrates
      (midazolam, rosuvastatin, and digoxin) and/or AZD5462 including the washout period between
      Period 2 and Period 3. Residency will commence on Day -1 and end on Day 20.

      A follow-up visit at Day 24 (+-1 Day) will be conducted via a phone call.
    

Intervention name(s): AZD5462; Midazolam; Rosuvastatin; Digoxin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Treatment Arm A: Participants will receive the IMP, AZD5462 Dose A starting on Day 6 and continued until Day 18 and the following approved medicinal products:
Midazolam
Rosuvastatin
Digoxin
Treatment Arm B: Participants will receive the IMP, AZD5462 Dose B starting on Day 6 and continued until Day 18 and the following approved medicinal products:
Midazolam
Rosuvastatin
Digoxin; Participants will receive a single dose of midazolam in the morning of Day 1 and in the morning of Day 15 in both the arms.; Participants will receive rosuvastatin as a single dose administered with digoxin at the same time in the morning of Day 2, Day 6, and in the morning of Day 16 in both the arms.; Participants will receive digoxin as a single dose administered with rosuvastatin at the same time in the morning of Day 2, Day 6, and in the morning of Day 16 in both the arms.
Intervention MeSH terms: Digoxin; Midazolam; Rosuvastatin Calcium
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cytochrome P450 enzyme 3A4; Organic Anion Transporting Polypeptide 1B1/1B3; Breast Cancer Resistance Protein; P-glycoprotein