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

Inclusion Criteria

• Between 18 and 60 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring (ECG and 24 hour Holter). A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator, in consultation with Medical Monitor if required, judges and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Body weight >= 50 Kilogram (kg) (110 pounds [lbs]) for men and >= 45 kg (99lbs) for women and body mass index (BMI) within the range 18 - 30 kg per square metre (m^2) (inclusive)
• Male or Female. Female with non-reproductive potential defined as, Pre-menopausal females with one of the following: Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral Oophorectomy, Documented Postmenopausal defined as 12 months of spontaneous amenorrhea
• Capable of giving signed informed consent.

Exclusion Criteria

• A blood pressure 1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is 450 milliseconds (msec). The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (~240 millilitre [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• Smoking more than 5 cigarettes per week and subjects must be able to abstain from smoking for a 24 hour period prior to dose and any time whilst in the clinical unit.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study treatment.
• A positive test for human immuno-deficiency virus (HIV) antibody
• A positive pre-study drug/alcohol screen.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within previous 3 months
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.