A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects
Condition: Hypertension, Pulmonary
MeSH terms: Hypertension, Pulmonary
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is designed to understand the relative bioavailability (proportion of the
      administered dose that is absorbed into the bloodstream) of several fixed dose combinations
      (FDCs) tablets of ambrisentan and tadalafil for further development and to provide
      pharmacokinetic (PK - what the body does to the drug) data to enable a pivotal bioequivalence
      (BE - the relationship between two preparations of the same drug in the same dosage form that
      have a similar bioavailability) study. Depending on formulation work, the study will allow up
      to 8 new FDCs to be compared with the reference of ambrisentan and tadalafil monotherapies.
      The study will also evaluate up to 2 of the new formulations, that may be taken in to a BE
      study, to be tested for any effect on pharmacokinetics of the FDC in both fed and fasted
      state. This is a single centre, Phase 1, single dose, randomised, open label crossover study
      with 3 study parts; each study part will have up to a 5 way crossover in healthy subjects.
      Part 1 of the study will evaluate four formulations of the FDC (ambrisentan 10 milligram [mg]
      + tadalafil 40 mg) and the reference of the 2 monotherapy components taken concurrently
      (ambrisentan 10 mg and tadalafil 40 mg) in the fasted stated. If successful formulations are
      identified in this part of the study, then they will be re-formulated and tested in part 2.
      If no successful formulations are identified in part 1 of the study, then part 2 will be
      utilized to look at up to 4 new FDC formulations. However, if only two formulations, or less,
      are evaluated in part 2 then the FDC formulations may be tested both fed and fasted to assess
      food effect and part 3 will not be required. If successful formulations are identified in
      this study part, then up to 2 of these may be tested, for food effect, in Part 3 if not
      already assessed in this part. Therefore, part 3 is optional and utility is dependent on the
      results of the previous study parts.
    


Intervention name(s): FDC (ambrisentan 10 mg-tadalafil 40 mg) single dose; Reference (ambrisentan 10 mg + tadalafil 40 mg given concurrently)
Intervention type(s): Drug; Drug
Intervention description(s): The four FDCs in part 1 will have the following formulation designation: FDC1, FDC2, FDC3 and FDC4. They are film-coated tablets. The dose will be administered orally. Study treatment for Part2 and Part 3 will be amended after Part 1 study; Ambrisentan is a film-coated tablet. Each tablet of ambrisentan contains 10 mg of ambrisentan, approximately 95 mg of lactose (as monohydrate), 0.25 mg of lecithin and 0.11 mg of Allura red AC Aluminium Lake. Tadalafil is also a film-coated tablet. Each tablet of Tadalafil contains 20 mg tadalafil and 233 mg lactose. Both the tablets will be administered orally concurrently.
Intervention MeSH terms: Ambrisentan; Tadalafil
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ambrisentan; Bioavailability; Tadalafil; Fixed Dose combination