A Phase 1 Bioavailability Study of Arbaclofen Placarbil Modified Release Formulations in Healthy Volunteers
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      Part 1

        -  To evaluate the pharmacokinetic (PK) profile of Arbaclofen Placarbil (AP) and R-baclofen
           following dosing of Arbaclofen Placarbil Modified Release (MR) Prototype A Tablet and
           Arbaclofen Placarbil MR Prototype B Tablet in healthy subjects

        -  To determine the relative bioavailability of AP and R-baclofen following dosing of
           Arbaclofen Placarbil MR Prototype A Tablet and Arbaclofen Placarbil MR Prototype B
           Tablet compared to the reference Arbaclofen Placarbil Sustained Release (SR) Tablets
           (low dose)

        -  To determine the relative bioavailability and PK of AP and R-baclofen following dosing
           of the selected MR prototype formulation(s) in the presence of beverage

        -  To provide additional information on the safety and tolerability of single doses of AP

      Part 2

        -  To evaluate the PK profile of AP and R-baclofen following dosing of Arbaclofen Placarbil
           MR Prototype Tablets in healthy subjects

        -  To determine the relative bioavailability and PK of AP and R-baclofen following dosing
           of Arbaclofen Placarbil MR Prototype Tablets compared to the reference Arbaclofen
           Placarbil Immediate Release (IR) Capsule

        -  To provide additional information on the safety and tolerability of single doses of AP

        -  To determine the relative bioavailability and PK of AP and R-baclofen following dosing
           of a selected MR prototype formulation in the fed state (optional)

        -  To explore a possible in vitro in vivo correlation/relationship (IVIVC/IVIVR) for the
           Arbaclofen Placarbil MR Prototype Tablet Formulations

      Part 3

        -  To determine the relative bioavailability of the selected Arbaclofen Placarbil MR
           Prototype Tablet in the presence of either beverage or food and/or

        -  To evaluate the PK profile (dose proportionality) of AP and R-baclofen following dosing
           of the selected Arbaclofen Placarbil MR Prototype A + B Tablet at different dose levels
           in healthy subjects

        -  To provide additional information on the safety and tolerability of single doses of AP
    

Detailed description: 
      For Parts 1, 2 and 3, participants will attend the clinical unit for a screening visit up to
      28 days before dosing. For each treatment period, eligible subjects will be admitted to the
      clinical unit on the evening before dosing (Day -1). Participants will receive each regimen
      in the morning of Day 1 and will remain on site until 48 h post-dose. There will be a minimum
      washout period of 7 days between administration of each regimen. Where interim decisions
      occur, the interval between periods will be sufficient to permit the decision process.

      Arbaclofen Placarbil MR Prototype Tablets will be administered in Part 1 and one prototype
      will be selected for development in Part 2 where the release rate of modified release (MR)
      prototype formulations will be optimised using a design space concept (at a fixed low dose).

      A selected MR prototype formulation from Part 2 may be administered in Part 3 at up to 4
      different dose levels (low, mid-low, mid-high, high). The suggested doses in Part 3 may be
      modified based on emerging safety and PK data from Part 2 of the study.

      In Parts 2 and 3, there will be an option to dose selected Arbaclofen Placarbil MR Prototype
      Tablets in the fed state.
    

Intervention name(s): Arbaclofen Placarbil SR; Arbaclofen Placarbil MR Prototype A; Arbaclofen Placarbil MR Prototype B; Arbaclofen Placarbil IR
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): One low dose oral tablet of Arbaclofen Placarbil sustained release (SR) in the fasted state.; One low dose oral tablet pf Arbaclofen Placarbil modified release (MR) Prototype A in the fasted state; this formulation may also be tested with 0.6 g/kg beverage diluted in orange juice; One low dose oral tablet of Arbaclofen Placarbil modified release (MR) Prototype B; this formulation may also be tested with 0.6 g/kg beverage diluted in orange juice; One low dose oral capsule of Arbaclofen Placarbil immediate release (IR) in the fasted state.
Intervention MeSH terms: Arbaclofen placarbil; Baclofen
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The Clinical Trial Authorisation application for this study describes a flexible protocol design using the formulation design space concept to allow decision-making in response to interim PK observations
Masking: None (Open Label)
Primary purpose: Basic Science