A Phase 1 Relative Bioavailability Study of Ambrisentan and Tadalfil Fixed Dose Combination Tablets in Healthy Subjects

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.

Conditions

• Hypertension, Pulmonary

Interventions

DRUG

FDC (ambrisentan 10 mg-tadalafil 40 mg) single dose

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

DRUG

Reference (ambrisentan 10 mg + tadalafil 40 mg given concurrently)

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.

Sponsors & Collaborators

• Covance Harrogate

  collaborator UNKNOWN

• Hammersmith Medicines Research

  collaborator OTHER

• GlaxoSmithKline

  lead INDUSTRY

Principal Investigators

• GSK Clinical Trials · GlaxoSmithKline

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-03-18

Primary Completion

2017-08-04

Completion

2017-08-04

Countries

• United Kingdom

Study Locations