A Study to Assess the Bioavailability of Different Formulations of AZD5718 and the Food Effect on the Selected Formulation of AZD5718 in Healthy Volunteers
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      In this study, the relative bioavailability of different formulations of AZD5718 will be
      determined in order to compare it with the formulation used in a previous Phase 2a study and
      confirm appropriate drug exposure. This study consist of 2 parts. In Part 1, 5 different
      formulations of AZD5718 would be provided to the participant in fasting condition in a
      randomized order. After evaluation of Part 1 a single formulation would be selected for
      dosing in fed condition in Part 2. Each participant will be involved in the study for
      approximately 5 to 6 weeks. Fourteen participants will be randomized to ensure at least 10
      evaluable participants at the end of the last treatment period.
    

Detailed description: 
      This is a Randomized, 6-period, 6-treatment, Single-dose, Open-label, Single-center,
      Crossover, phase I Study to Assess the Relative Bioavailability of Different Formulations of
      AZD5718 and the Food Effect on the Selected Formulation of AZD5718 in Healthy Volunteers. In
      this study, the relative bioavailability of different formulations of AZD5718 will be
      determined in order to compare it with the formulation used in a previous Phase 2a study and
      confirm appropriate drug exposure. The optimal pharmacokinetic (PK) profile of AZD5718 is
      currently not known but working hypothesis is that a flatter PK profile will deliver the same
      efficacy at a lower dose/exposure compared to a fluctuating AZD5718 profile. Thus,
      formulations with different release rates will be evaluated. Potential food effect of a
      selected formulation would be determined in order to provide appropriate dose and dosing
      instructions for further development of AZD5718. This study would consist of 2 parts. In Part
      1, 5 different formulations of AZD5718 would be provided to the participants in fasting
      condition in a randomized order. After evaluation of Part 1 a single formulation would be
      selected for dosing in fed condition in Part 2. Part 1 of the study will be an open-label,
      randomized, 5-period, 5-treatment, single dose crossover study in 14 healthy participants
      (males and females of non-childbearing potential), performed at a single study center to
      ensure that at least 10 participants are evaluable. Each participant would be randomized to 1
      of 10 treatment sequence according to a Williams design to receive the 5 treatments as
      following: Form 1 of AZD5718 tablets, Treatment B: Form 2 of AZD5718 tablets, Treatment C:
      Form 3 of AZD5718 tablets, Treatment D: Form 4 of AZD5718 tablets, and Treatment E: Form 5 of
      AZD5718 tablets. Participants will receive 1 treatment per treatment period. During each
      treatment period, participants would be dosed following an overnight fast of at least 10
      hours. No fluids will be allowed apart from water which can be given until 2 hours before
      administration of the investigational medicinal product (IMP) and then from 1 hours after
      administration of the IMP. The dose would be administered with 240 mL of water. A standard
      meal would be given 4 hours after administration of the IMP. Participants should not lie
      fully supine (unless specified for certain assessments) for 4 hours after dosing. After
      completion the PK evaluation in Part 1, the formulation for Part 2 would be selected. At
      least 10 participants from Part 1 will be included in Part 2, to ensure that at least 8
      participants are evaluable. For each participant included in Part 2, there would be minimum
      period of at least 2 weeks between the last dose of IMP in Part 1 and the dose of IMP in Part
      2. During the treatment period in Part 2, participants would be dosed with the selected
      formulation of IMP with food. Participants would fast at least 10 hours prior to receiving
      the test meal. Participants should start the recommended meal 30 minutes prior to
      administration of the IMP. Participants would be required to consume the meal in 25 minutes;
      however, the IMP should be administered 30 minutes after start of the meal with 240 mL of
      water. No fluids would be allowed apart from water which can be given until 1 hour before
      administration of the IMP and then from 2 hours after administration of the IMP. Each
      participant will be involved in the study for approximately 5 to 6 weeks.
    

Intervention name(s): Form 1 of AZD5718 tablets; Form 2 of AZD5718 tablets; Form 3 of AZD5718 tablets; Form 4 of AZD5718 tablets; Form 5 of AZD5718 tablets; Selected form (Form 2 - 5) of AZD5718 tablets
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): The participants will be dosed with Form 1 of AZD5718 following an overnight fast of at least 10 hours.; The participants will be dosed with Form 2 of AZD5718 following an overnight fast of at least 10 hours.; The participants will be dosed with Form 3 of AZD5718 following an overnight fast of at least 10 hours.; The participants will be dosed with Form 4 of AZD5718 following an overnight fast of at least 10 hours.; The participants will be dosed with Form 5 of AZD5718 following an overnight fast of at least 10 hours.; The participant will be administered with selected form (one of Form 2-5) of AZD5718 tablets 30 minutes after start of the meal.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: vasoactive leukotrienes by leukocytes; bioavailability