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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02688387
• Collaborator: Covance Harrogate (Other), Hammersmith Medicines Research (Other)
• Enrollment: 112
• Location: 1
• Arms: 3
• Actual Duration (Months): 16.6
• Patients Per Site Per Month: 6.8

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension, Pulmonary	Drug: FDC (ambrisentan 10 mg-tadalafil 40 mg) single dose; Drug: Reference (ambrisentan 10 mg + tadalafil 40 mg given concurrently)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study to Demonstrate the Relative Bioavailability of Fixed Dose Combinations of Ambrisentan and Tadalafil in Healthy Subjects
• Actual Study Start Date: Mar 18, 2016
• Actual Primary Completion Date: Aug 4, 2017
• Actual Study Completion Date: Aug 4, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Enrolled subjects will receive single oral dose of 4 FDCs i.e., FDC1, FDC2, FDC3 and FDC4, and reference formulations of the 2 monotherapy components taken concurrently in the fasted state. The FDC and reference formulations contains 10 mg ambrisentan and 40 mg tadalafil. Each dosing period will be separated by 7 days wash out period.	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.
Experimental: Part 2 Enrolled subjects will receive single oral dose of 4 FDCs i.e., FDC5, FDC6, FDC7 and FDC8, and reference formulations of the 2 monotherapy components taken concurrently in the fasted state. The FDCs and reference formulations contains 10 mg ambrisentan and 40mg Tadalafil. OR Subjects will receive single dose of two FDCs from Part 1 in fed and fasted state. Each dosing period will be separated by 7 days wash out period.	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.
Experimental: Part 3 Enrolled subjects will receive single oral dose of 2 FDCs from Part 2 in fed and fasted state. The FDCs contains 10 mg ambrisentan and 40 mg Tadalafil. Each dosing period will be separated by 7 days wash out period.	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

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Concentration (Cmax) of Ambrisentan and Tadalafil in FDC (Ambrisentan 10 mg + Tadalafil 40 mg) and Montherapies (Ambrisentan 10 mg & Tadalafil 40 mg) - Part 1 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   Cmax is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples were collected at the indicated time points for analysis of ambrisentan and tadafil. The analysis was done under fasting condition post single dose. There is no formal hypotheses tested for Part 1 of the study. The analysis was performed on Pharmacokinetic (PK) parameter population, which included all participants who provided PK parameter data.

2. Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to Infinite (Inf) Time, AUC (0-inf) of Ambrisentan and Tadalafil in FDC (Ambrisentan 10 mg + Tadalafil 40 mg) and Montherapies (Ambrisentan 10 mg & Tadalafil 40 mg) - Part 1 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for ambrisentan and tadafil. Blood samples were collected at the indicated time-points. The analysis was done under fasting condition post single dose. There is no formal hypothesis tested for Part 1 of the study.

3. AUC From Time of Dose to Last Measurable Concentration (AUC [0-t]), in FDC, (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fasting- Part 1 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   AUC (0-t), was defined as, the AUC measured from the time of dose to the last measurable concentration. Blood samples of 2.7 mL and 2 mL, were collected for ambrisentan and tadafil respectively. The plasma samples at Part 1, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours. The analysis was done under fasting condition post single dose. The PK Parameter Population was used for analysis. There is no formal hypotheses tested for Part 1 of the study.

4. Cmax of Ambrisentan and Tadalafil in FDC (Ambrisentan 10 mg + Tadalafil 40 mg) and Montherapies (Ambrisentan 10 mg & Tadalafil 40 mg) - Part 2 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   Cmax is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples were collected at the indicated time-points, of Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose. The analysis was done under fasting condition post single dose. There is no formal hypotheses tested for Part 2 of the study. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

5. AUC (0 - Inf) for FDC, (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fasting- Part 2 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for ambrisentan and tadafil. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 2, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis, was done under fasting condition post single dose. PK parameter Populatio was used for analysis. There is no formal hypotheses tested for Part 2 of the study. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

6. AUC (0-t) for FDC, (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fasting- Part 2 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   AUC (0-t), was defined as, the AUC measured from the time of dose to the last measurable concentration. Blood samples of 2.7 mL and 2 mL, were collected for ambrisentan and tadafil respectively. The plasma samples for Part 2, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours. The analysis was done under fasting condition post single dose. PK parameter Population was used for analysis. There is no formal hypotheses tested for Part 2 of the study. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

7. Cmax for Ambrisentan and Tadalafil, Following Candidate FDC (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fed and Fasted Conditions-Part 3A [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   Cmax is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3A, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fed and fasting condition post single dose. PK parameter population was used.

8. AUC (0-inf) for Ambrisentan and Tadalafil, Following Candidate FDC (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fed and Fasted Conditions-3A [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for ambrisentan and tadafil. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3A, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48 and 72 hours post-dose. The analysis, was done under fed and fasting conditions post single dose. PK parameter population was used.

9. AUC (0-t) for Ambrisentan and Tadalafil, Following Candidate FDC (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fed and Fasted Conditions-Part 3A [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   AUC (0-t), was defined as, the AUC measured from the time of dose to the last measurable concentration. Blood samples of 2.7 mL and 2 mL, were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3A, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fed and fasting condition post single dose. PK parameter population was used.

10. Cmax for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 40 mg) Under Fasted Conditions-3B [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

    Cmax is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fasting condition post single dose.

11. AUC (0-inf) for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 40 mg) Under Fasted Conditions-3B [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

    AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for ambrisentan and tadafil. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36,48 and 72 hours post-dose. The analysis was done under fasting condition post single dose. PK Parameter Population was used for analysis.

12. AUC (0-t) for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 40 mg) Under Fasted Conditions-3B [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

    AUC (0-t), was defined as, the AUC measured from the time of dose to the last measurable concentration. Blood samples of 2.7 mL and 2 mL, were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fasting condition post single dose. PK parameter population was used for analysis.

13. Cmax for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 20 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 20 mg) Under Fasted Conditions-3B [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

    Cmax is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fasting condition post single dose. PK parameter population was used.

14. AUC (0-inf) for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 20 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 20 mg) Under Fasted Conditions-3B [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

    AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for ambrisentan and tadafil. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis, was done under fasting conditions post single dose. PK parameter population was used for analysis.

15. AUC (0-t) for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 20 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 20 mg) Under Fasted Conditions- Part 3B [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

    AUC (0-t), was defined as, the AUC measured from the time of dose to the last measurable concentration. Blood samples of 2.7 mL and 2 mL, were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fasting condition post single dose. PK parameter population was used for analysis.

Secondary Outcome Measures

1. Time Taken to Reach Maximum Concentration (Tmax) for Ambrisentan and Tadalafil in FDC and Reference Treatment - Part 1 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   Serial blood samples were collected at the indicated time-points. In Part 3A, tmax was determined for ambrisentan and tadalafil when administered in FDC (10mg/40mg) under fed state and fasted state and as reference monotherapies (ambrisentan 10 mg and tadalafil 40 mg). PK parameter population was used to measure the tmax.

2. Time Taken to Reach Maximum Concentration (Tmax) for Ambrisentan and Tadalafil in FDC and Reference Treatment - Part 2 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   Serial blood samples were collected at the indicated time-points. In Part 3A, tmax was determined for ambrisentan and tadalafil when administered in FDC (10mg/40mg) under fed state and fasted state and as reference monotherapies (ambrisentan 10 mg and tadalafil 40 mg). PK parameter population was used to measure the tmax. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

3. Time Taken to Reach Maximum Concentration (Tmax) for Ambrisentan and Tadalafil in FDC and Reference Treatment - Part 3A [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   Serial blood samples were collected at the indicated time-points. In Part 3A, tmax was determined for ambrisentan and tadalafil when administered in FDC (10mg/40mg) under fed state and fasted state and as reference monotherapies (ambrisentan 10 mg and tadalafil 40 mg). PK parameter population was used to measure the tmax.

4. Time Taken to Reach Maximum Concentration (Tmax) for Ambrisentan and Tadalafil in FDC and Reference Treatment - Part 3B [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   Serial blood samples were collected at the indicated time-points. In Part 3B, tmax was determined for ambrisentan and tadalafil when administered in FDC (10mg/40mg) under fed state and fasted state and as reference monotherapies (ambrisentan 10 mg and tadalafil 40 mg). PK parameter population was used to measure the tmax.

5. Plasma Half Life (t1/2) for Ambrisentan and Tadalafil in FDC and Reference Treatment Under Fed and Fasted Condition- Part1 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   t1/2 is defined as the time required by the concentration of the drug to reach half of its original value.

6. Plasma t1/2 for Ambrisentan and Tadalafil in FDC and Reference Treatment Under Fed and Fasted Condition- Part 2 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   t1/2 is defined as the time required by the concentration of the drug to reach half of its original value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

7. Plasma t1/2 for Ambrisentan and Tadalafil in FDC and Reference Treatment Under Fed and Fasted Condition- Part 3A [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose]

   t1/2 is defined as the time required by the concentration of the drug to reach half of its original value. The serial blood samples were assessed at specified timepoints.

8. Plasma t1/2 for Ambrisentan and Tadalafil in FDC and Reference Treatment Under Fed and Fasted Condition- Part 3B [Pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48, and 72 hours postdose]

   t1/2 is defined as the time required by the concentration of the drug to reach half of its original value. The serial blood samples were assessed at specified timepoints.

9. Change From Baseline in Vital- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), Part 1 [Baseline and Up to Day 3]

   Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for SBP and DBP. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1. Safety population included all the participants enrolled into the study who received atleast one dose of investigational product.

10. Change From Baseline in Vital Signs-Heart Rate, Part 1 [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Heart rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

11. Change From Baseline in Vital- Temperature, Part 1 [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for temperature. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

12. Change From Baseline in Vital Signs-Respiratory Rate, Part 1 [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Respiratory rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

13. Change From Baseline in Vital- SBP and DBP, Part 2 [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for SBP and DBP. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

14. Change From Baseline in Vital Signs-Heart Rate, Part 2 [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Heart rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1. Safety population included all the participants enrolled into the study who received atleast one dose of investigational product.

15. Change From Baseline in Vital- Temperature, Part 2 [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for temperature. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1. Safety population included all the participants enrolled into the study who received atleast one dose of investigational product.

16. Change From Baseline in Vital Signs-Respiratory Rate, Part 2 [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Respiratory rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

17. Change From Baseline in Vital- SBP and DBP, Part 3A [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for SBP, DBP. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

18. Change From Baseline in Vital Signs-Heart Rate, Part 3A [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Heart rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

19. Change From Baseline in Vital- Temperature, Part 3A [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for temperature. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

20. Change From Baseline in Vital Signs-Respiratory Rate, Part 3A [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Respiratory rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

21. Change From Baseline in Vital- SBP and DBP, Part 3B [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for SBP and DBP. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

22. Change From Baseline in Vital Signs-Heart Rate, Part 3B [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for HR. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

23. Change From Baseline in Vital- Temperature, Part 3B [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for temperature. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

24. Change From Baseline in Vital Signs-Respiratory Rate, Part 3-B [Baseline and Up to Day 3]

    Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Respiratory rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.

25. Number of Participants With Abnormal Electrocardiogram (ECG) Findings, -Part 1 [Up to Day 3]

    12-lead ECG, was measured in semi-supine position after 5 minutes rest. The data for worst case post-baseline has been reported. Data values for the participants with abnormal clinically significant values are reported. Safety population was used for analysis.

26. Number of Participants With Abnormal ECG Findings, -Part 2 [Up to Day 3]

    12-lead ECG, were measured in semi-supine position after 5 minutes rest. It was conducted as triplicate at screen and baseline, whereas single measure at other times, unless out of range then triplicates were performed. The data for worst case post-baseline has been reported. Data values for the participants with abnormal clinically significant values are reported. Safety population was used for analysis.

27. Number of Participants With Abnormal ECG Findings, -Part 3A [Up to Day 3]

    12-lead ECG, were measured in semi-supine position after 5 minutes rest. It was conducted as triplicate at screen and baseline, whereas single measure at other times, unless out of range then triplicates were performed. The data for worst case post-baseline has been reported. Data values for the participants with abnormal clinically significant values are reported. Safety population was used for analysis.

28. Number of Participants With Abnormal ECG Findings, -Part 3B [Up to Day 3]

    12-lead ECG, were measured in semi-supine position after 5 minutes rest. It was conducted as triplicate at screen and baseline, whereas single measure at other times, unless out of range then triplicates were performed. The data for worst case post-baseline has been reported. Data values for the participants with abnormal clinically significant values are reported. Safety population was used for analysis.

29. Number of Participants With Hematology Values of Potential Clinical Importance (PCI)- Part1 [Up to Day 3]

    Blood samples were collected from the participants for analysis of hematology parameters like hematocrit, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.

30. Number of Participants With Hematology Values of PCI - Part 2 [Day 2]

    Blood samples were collected from the participants for analysis of hematology parameters like hematocrit, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.

31. Number of Participants With Hematology Values of PCI - Part 3A [Day 2]

    Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of hematology parameters like hematocrit, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. It was conducted at Day 2 (48 hours). The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.

32. Number of Participants With Hematology Values of PCI - Part 3B [Day 2]

    Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of hematology parameters like hematocrit, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. It was conducted at Day 2 (48 hour). The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.

33. Number of Participants With Clinical Chemistry Values of PCI- Part1 [Day 2]

    Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of clinical chemistry parameters like glucose, calcium, albumin, sodium and potassium. The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.

34. Number of Participants With Clinical Chemistry Values of PCI- Part 2 [Day 2]

    Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of clinical chemistry parameters like glucose, calcium, albumin, sodium and potassium. It was collected at Day 2 (48 hour). The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.

35. Number of Participants With Clinical Chemistry Values of PCI- Part 3A [Day 2]

    Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of clinical chemistry parameters like glucose, calcium, albumin, sodium and potassium. It was collected at (48 hour). The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.

36. Number of Participants With Clinical Chemistry Values of PCI- Part 3B [Day 2]

    Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of clinical chemistry parameters like glucose, calcium, albumin, sodium and potassium. It was collected at Day 2 (48 hour). The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.

37. Number of Participants With Abnormal Urinalysis Results by Dipstick Method-Part 1 [Up to Day 2]

    Urine samples were collected at Day -1 (Baseline) and 48 hour, from the participants for urinalysis, by standard dipstick method. The parameters analyzed were ketones, glucose, occult blood, and protein. The number of participants with parameters detected as trace-lysed, trace-intact, trace, 2+ and 1+ was reported. Safety Population was used for analysis.

38. Number of Participants With Urinalysis Results by Dipstick Analysis-Part 2 [Up to Day 2]

    Urine samples were collected at Day -1 (Baseline) and 48 hour, from the participants for urinalysis, by standard dipstick method. The parameters analyzed were ketones, glucose, occult blood, and protein. The number of participants with parameters detected as trace-lysed, trace-intact, trace, 2+ and 1+ was reported. Safety Population was used for analysis

39. Number of Participants With Urinalysis Results by Dipstick Analysis-Part 3A [Up to Day 2]

    Urine samples were collected at Day -1 (Baseline) and 48 hour, from the participants for urinalysis, by standard dipstick method. The parameters analyzed were ketones, glucose, occult blood, and protein. The number of participants with parameters detected as trace-lysed, trace-intact, trace, 2+ and 1+ was reported. Safety Population was used for analysis.

40. Number of Participants With Urinalysis Results by Dipstick Analysis-Part 3B [Up to Day 2]

    Urine samples were collected at Day -1 (Baseline) and 48 hour, from the participants for urinalysis, by standard dipstick method. The parameters analyzed were ketones, glucose, occult blood, and protein. The number of participants with parameters detected as trace-lysed, trace-intact, trace, 2+ and 1+ was reported. Safety Population was used for analysis.

41. Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)-Part 1 [Up to 42 days]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Safety population was used for analysis.

42. Number of Participants With SAEs and AEs-Part 2 [Up to 35 days]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Safety population was used for analysis.

43. Number of Participants With SAEs and AEs-Part 3A [Up to 44 days]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Safety population was used for analysis.

44. Number of Participants With SAEs and AEs-Part 3B [Up to 44 days]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Safety population was used for analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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 <100/55 millimetre of Mercury (mm Hg).

• Haemoglobin (Hb) below normal range: Hb <133 (gram per litre) g/L for males and Hb <114 g/L for females

• Alanine amino transferase (ALT) and bilirubin >1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is <35 percentage [%]).

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)

• Corrected QT (QTc) >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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	London		United Kingdom	NW10 7EW

Sponsors and Collaborators

• GlaxoSmithKline
• Covance Harrogate
• Hammersmith Medicines Research

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - May 25, 2017
• Statistical Analysis Plan - Jul 31, 2017

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02688387
• Other Study ID Numbers: 201964
• First Posted: Feb 23, 2016
• Last Update Posted: Jan 22, 2019
• Last Verified: Jul 1, 2018

• Keywords provided by GlaxoSmithKline: Ambrisentan; Bioavailability; Tadalafil; Fixed Dose combination
• Additional relevant MeSH terms: Hypertension, Pulmonary; Ambrisentan; Tadalafil

Study Results

Participant Flow

Recruitment Details	This was a single dose, randomized, open-label, crossover study in healthy participants. A total of 112 healthy participants were randomized and received the study treatment. The study was conducted at a single center in the United Kingdom.
Pre-assignment Detail	A total of 174 participants were screened, of which 59 were screen failures and 3 participants were reserve participants. Thus 112 participants were randomized. The study, was conducted in three parts: Part 1 (5 way crossover) and Parts 2 and 3 (A and B), followed 4 way crossover design.

Arm/Group Title	Part 1, F2/ F3/ F1/ F4/ R	Part 1, R/ F1/ F4/ F2/ F3	Part 1, F4/ F3/ R/ F2/ F1	Part 1, F2/ F1/ F3/ R/ F4	Part 1, F3/ F2/ F4/ F1/ R	Part 1, F1/ F2/ R/ F3/ F4	Part 1, F3/ F4/ F2/ R/ F1	Part 1, F4/ R/ F3/ F1/ F2	Part 1, R/ F4/ F1/ F3/ F2	Part 1, F1/ R/ F2/ F4/ F3	Part 2, R/ FG1/ FG3/ FG2	Part 2, FG1/FG2/R/ FG3	Part 2, FG2/ FG3/ FG1/ R	Part 2, FG3/ R/ FG2/ FG1	Part 3A, X2/ R2/ R1/ X1	Part 3A, ,X1/ R1/ R2/ X2	Part 3A, R1/ X2/ X1/ R2	Part 3A, ,R2/ X1/ X2/ R1	Part 3B, Y1/ R3/ R4/ Y2	Part 3B, R3/ Y2/ Y1/ R4	Part 3B, Y2/ R4/ R3/ Y1	Part 3B, R4/ Y1/ Y2/ R3
Arm/Group Description	The eligible participants in the Sequence (F2/ F3/ F1/ F4/ R) received a single oral dose of fixed dose combination (FDC) for GSK3380154 (ambrisentan 10 milligram [mg] + tadalafil 40 mg). Participants received single oral dose F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg Sodium laurilsulfate [SLS]) during Period 1, followed by single oral dose F3 (FDC 3- GSK3380154, TAB-A, Tablet Weight 560mg/2mg SLS) during Period 2, followed by single oral dose F1(FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS) during Period 3, followed by a single oral dose of F4 (FDC4- GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS) during Period 4, which was followed by a single oral dose of R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil, taken concurrently, during Period 5. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (R/ F1/ F4/ F2/ F3), received a single oral dose of FDC for GSK3380154 (ambrisentan 10 mg + tadalafil 40 mg). Participants received single oral dose of R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil, taken concurrently, during Period 1, followed by single oral dose of F1(FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS) during Period 2, followed by a single oral dose of F4 (FDC4- GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS) during Period 3, followed by single oral dose F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS during Period 4, followed by single oral dose F3 (FDC 3- GSK3380154, TAB-A, Tablet Weight 560mg/2mg SLS) during Period 5.Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (F4/ F3/ R/ F2/ F1), received a single oral dose of FDC for GSK3380154 (ambrisentan 10 mg + tadalafil 40 mg). Participants received single oral dose of F4 (FDC4- GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS) during Period 1, followed by single oral dose F3 (FDC 3- GSK3380154, TAB-A, Tablet Weight 560mg/2mg SLS) during Period 2, followed by single oral dose of R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil, taken concurrently, during Period 3, followed by single oral dose F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, during Period 4, followed by single oral dose of F1(FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS), during Period 5. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (F2/ F1/ F3/ R/ F4), received a single oral dose of FDC for GSK3380154 (ambrisentan 10 mg + tadalafil 40 mg). Participants received single oral dose of F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, during Period 1, followed by single oral dose of F1(FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS), during Period 2, followed by single oral dose F3 (FDC 3- GSK3380154, TAB-A, Tablet Weight 560mg/2mg SLS) during Period 3, followed by single oral dose of R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil, taken concurrently, during Period 4, followed by single oral dose of F4 (FDC4- GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS) during Period 5. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (F3/ F2/ F4/ F1/ R), received a single oral dose of FDC for GSK3380154 (ambrisentan 10 mg + tadalafil 40 mg). Participants received single oral dose of F3 (FDC 3- GSK3380154, TAB-A, Tablet Weight 560mg/2mg SLS), during Period 1, followed by a single oral dose of F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, during Period 2, followed by single oral dose of F4 (FDC4- GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS) during Period 3, followed by single oral dose of F1(FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS), during Period 4, followed by single oral dose of R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil, taken concurrently, during Period 5. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (F1/ F2/ R/ F3/ F4), received a single oral dose of FDC for GSK3380154 (ambrisentan 10 mg + tadalafil 40 mg). Participants received single oral dose of F1(FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS) during Period 1, followed by a single oral dose of F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, during Period 2, followed by single oral dose of R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil, taken concurrently, during Period 3, followed by a single oral dose of F3 (FDC 3- GSK3380154, TAB-A, Tablet Weight 560mg/2mg SLS), during Period 4, followed by single oral dose of F4 (FDC4- GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS)during Period 5. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (F3/ F4/ F2/ R/ F1), , received a single oral dose of FDC for GSK3380154 (ambrisentan 10 mg + tadalafil 40 mg). Participants received single oral dose of F3 (FDC 3- GSK3380154, TAB-A, Tablet Weight 560mg/2mg SLS), during Period 1, followed by single oral dose of F4 (FDC4- GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS) during Period 2, followed by a single oral dose of F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, during Period 3, followed by a single oral dose of F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, during Period 4, followed by received single oral dose of F1(FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS) during Period 5. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (F4/ R/ F3/ F1/ F2), received a single oral dose of FDC for GSK3380154 (ambrisentan 10 mg + tadalafil 40 mg). Participants received single oral dose of F4 (FDC4- GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS)during Period 1, followed by a single oral dose of R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil, taken concurrently during Period 2,followed by a single oral dose of F3 (FDC 3- GSK3380154, TAB-A, Tablet Weight 560mg/2mg SLS), during Period 3, followed single oral dose of F1(FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS), during Period 4, followed by a single oral dose of F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, during Period 5. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (R/ F4/ F1/ F3/ F2), received a single oral dose of FDC for GSK3380154 (ambrisentan 10 mg + tadalafil 40 mg). Participants received single oral dose of R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil, taken concurrently during Period 1, followed by a single oral dose of F4 (FDC4- GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS) during Period 2, followed single oral dose of F1(FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS), during Period 3, followed by a single oral dose of F3 (FDC 3- GSK3380154, TAB-A, Tablet Weight 560mg/2mg SLS), during Period 4, followed by a s ingle oral dose of F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, during Period 5. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (F1/ R/ F2/ F4/ F3), received a single oral dose of FDC for GSK3380154 (ambrisentan 10 mg + tadalafil 40 mg). Participants received single oral dose of F1(FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS),during Period 1, followed by single oral dose of R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil, taken concurrently during Period 2, followed by a s ingle oral dose of F2 (FDC 2-GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, during Period 3, followed by a single oral dose of F4 (FDC4- GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS) during Period 4, followed by a single oral dose of F3 (FDC 3- GSK3380154, TAB-A, Tablet Weight 560mg/2mg SLS), during Period 5. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (R/ FG1/ FG3/ FG2) were administered the 2 monotherapies ambrisentan and tadalafil concurrently, during Period 1, this was followed by single oral dose of FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg), with formulation selected from Part 1, during Period 2, this was followed by the single oral dose of FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1 during Period 3, this was followed by single oral dose of the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1, administered during Period 4. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (FG1/FG2/R/ FG3) were administered single oral dose of FG1 given as FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg), with formulation selected from Part 1, during Period 1, this was followed by the single oral dose of FG2 given as FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1 during Period 2, this was followed by the 2 monotherapies R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil concurrently, from the formulation selected from Part 1, given during Period 3, this was followed by single oral dose of FG3 given as FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1, administered during Period 4. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (FG2/ FG3/ FG1/ R), were administered single oral dose of FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1 during Period 1, this was followed by single oral dose of the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1, administered during Period 2, this was followed by single oral dose of FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg), with formulation selected from Part 1, during Period 3, this was followed by the 2 monotherapies R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil concurrently, from the formulation selected from Part 1, given during Period 4. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	The eligible participants in the Sequence (FG3/ R/ FG2/ FG1),were administered with single oral dose of the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1, administered during Period 1, this was followed by the 2 monotherapies R, a Reference- single monotherapies of 10 mg ambrisentan and 20 mg of tadalafil concurrently, from the formulation selected from Part 1, given during Period 2, this was followed by single oral dose of FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1 during Period 3, this was followed by single oral dose of FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg), with formulation selected from Part 1, during Period 4. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 7-Days.	Eligible participants received single oral dose of X2 as FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (granular formulation selected from Part 2), under fasted state during Period 1, followed by single oral dose of R2 where participants had received 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state during Period 2, this was followed by a single oral dose of R1 where participants had received 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state, comprising of high fat diet during Period 3, followed by a single oral dose of X1 where participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state, which comprised of high fat diet, during Period 4. Overall treatment period was of 4-weeks. Each dose taken either under fed or fasted condition and separated by washout period of 10-Days.	Eligible participants received single oral dose of X1 where participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state, which comprised of a high fat diet, during Period 1, followed by single oral dose of R1 where participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state, comprising of high fat diet during Period 2, followed by single oral dose of R2 where participants had received 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state during Period 3, followed by single oral dose of X2 as FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state during Period 4. Overall treatment period was of 4-weeks. Each dose taken either under fed or fasted condition and separated by washout period of 10-Days.	Eligible participants were administered single oral dose of R1 where participants had received 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state, comprising of high fat diet during Period 1, followed by single oral dose of X2 as FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state during Period 2, followed by single oral dose of X1 where participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state, comprising high fat diet, during Period 3, followed by single oral dose of R2 where participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state during Period 4. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 10-Days.	Eligible participants were administered single oral dose of R2 where participants had received 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state during Period 1, followed by single oral dose of X1 where participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state, which comprised of high fat diet, during Period 2, followed by single oral dose of X2 as FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (granular formulation selected from Part 2), under fasted state during Period 3, followed by single oral dose of R1 where participants had received 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state, comprising high fat diet during Period 4. Overall treatment period was of 4-weeks. Each dose was taken under fed or fasted condition and separated by washout period of 10-Days.	The eligible participants in the Sequence (Y1/ R3/ R4/ Y2), where participants for Y1 dose were administered a single oral dose of FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose during Period 1, this was followed by a single oral dose of R3 the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg during Period 2, this was followed by a single oral dose of R4, where the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state, during Period 3, this was followed by Y2 dose where the participants received a single oral dose of received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state, during Period 4. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 10-Days.	The eligible participants in the Sequence (R3/ Y2/ Y1/ R4), where the participants for R3 dose were administered a single oral dose of the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose, during Period 1, this was followed by the Y2 dose, where the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose during Period 2, this was followed by the Y1 dose where the participants were administered a single oral dose of FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose during Period 3, this was followed by a single oral dose of R4, where the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state, during Period 4. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 10-Days.	The eligible participants in the Sequence (Y2/ R4/ R3/ Y1), received single oral dose of Y2 where the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose during Period 1, this was followed by a single oral dose of R4, where the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state, during Period 2, this was followed by a single oral dose of R3 dose where participants were administered a single oral dose of the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state, during Period 3, this was followed by the Y1 dose where the participants were administered a single oral dose of FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose during Period 4. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 10-Days.	The eligible participants in the Sequence (R4/ Y1/ Y2/ R3), received single oral dose of R4, where the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state, during Period 1, this was followed by the Y1 dose where the participants were administered a single oral dose of FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose during Period 2, this was followed by single oral dose of Y2 where the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose during Period 3, this was followed by a single oral dose of R3 dose where participants were administered a single oral dose of the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state, during Period 4. Overall treatment period was of 4-weeks. Each dose was taken under fasted condition and separated by a washout period of 10-Days.
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	3	3	4	3	3	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	3	3	3	2	3	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	3	3	3	2	3	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	3	2	3	2	3	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	3	2	3	2	3	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	3	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	3	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	3	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	3	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	3	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	3	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	2	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	2	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	2	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	2	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	2	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	2	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
COMPLETED	2	2	2	2	2	2	2	2	2	2	0	0	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	6	5	5	5	0	0	0	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	5	5	5	5	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	9	8	8	8	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	8	8
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	7	8
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	8	7	8
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	7	7	6	8
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0
Period Title: Part 1, Period 1 (up to 6 Days)
STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	7	7	6	8
COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	7	7	6	8
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part 1	Part 2	Part 3A	Part 3B	Total
Arm/Group Description	In Part 1, there were 5 dosing sessions of four formulations of the FDCs (ambrisentan 10 mg + tadalafil 40 mg) (F1, F2, F3, F4) and 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg (R) which were administered concurrently . The participants received a single oral dose of formulation or the reference during each session. All the doses were taken in fasted condition. The treatment period for Part 1 was of 4-weeks, post which there was a follow-up period of 14 days (which included 7-days washout)	This comprised of 4 dose sessions, of 3 different granulation sizes for a single FDC (ambrisentan 10 mg +tadalafil 40 mg) compared to the reference of the 2 monotherapy components taken concurrently (ambrisentan 10 mg & tadalafil 40 mg), to evaluate the bioavailability. This part of the study provided data for 3 granulation size forms of a single FDC formulation selected from Part 1. The participants received a single oral dose during each session. All the doses were taken in fasted condition. The treatment period for Part 2 was of 4-weeks, post which a follow-up period of 14 days (which included 7-days washout). Part 2 had FG1, FG2, FG3 which are Ambrisentan and Tadalafil FDCs (10mg/40mg). R is ambrisentan and tadalafil monotherapies taken concurrently (10mg/40mg).	This comprised of 4 dose sessions of the FDC against the reference ambrisentan 10 mg + tadalafil 40mg monotherapies in the fed and fasted state, taken to evaluate the bioequivalence. The participants received a single oral dose during each session, taken under fed and fasted conditions. The fed arms of this part of the study received a standard high fat breakfast. The treatment period of Part 3A was of 4-weeks, post which a follow-up period of 14 days (which included 10-days washout). In Part 3A, X1, X2 are ambrisentan and tadalafil FDCs (10mg/40mg),where X1 is under fed state and X2 is under fasted state. R1, R2 are Ambrisentan and Tadalafil monotherapies taken concurrently(10mg/40mg), where R1 is under fed state and R2 is under fasted state.	This study part comprised of 4 dose sessions which assessed the bioequivalence of the two FDC dose strengths, (ambrisentan 5 mg + tadalafil 40mg and ambrisentan 5 mg + tadalafil 20mg) against the reference ambrisentan 5 mg + tadalafil 40mg monotherapies and ambrisentan 5 mg + tadalafil 20mg monotherapies in the fasted state. The treatment period of Part 3B was of 4-weeks, post which there was a follow-up period of 14 days (which included 10-days washout). In the Part 3B, Y1, Y2 are ambrisentan and tadalafil FDCs, under fasted state, where Y1 is 5mg/40mg and Y2 is 5mg/20mg and R3, R4 are ambrisentan and tadalafil monotherapies taken concurrently, under fasted state, where R3 is 5mg/40mg and R4 is 5mg/20mg.	Total of all reporting groups
Overall Participants	26	21	33	32	112
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	37.7 (11.68)	36.8 (12.07)	37.3 (10.36)	30.9 (12.05)	35.5 (11.71)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	1 3.1%	1 0.9%
Male	26 100%	21 100%	33 100%	31 96.9%	111 99.1%
Race/Ethnicity, Customized (Count of Participants)
Asian-Central/South Asian Heritage	0 0%	0 0%	2 6.1%	0 0%	2 1.8%
Asian- South East Asian heritage	0 0%	0 0%	1 3%	0 0%	1 0.9%
Black Or African American	3 11.5%	1 4.8%	5 15.2%	8 25%	17 15.2%
White - Arabic/North African Heritage	0 0%	0 0%	0 0%	1 3.1%	1 0.9%
White/Caucasian/European Heritage	23 88.5%	20 95.2%	25 75.8%	22 68.8%	90 80.4%
Multiple-Asian and White	0 0%	0 0%	0 0%	1 3.1%	1 0.9%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Concentration (Cmax) of Ambrisentan and Tadalafil in FDC (Ambrisentan 10 mg + Tadalafil 40 mg) and Montherapies (Ambrisentan 10 mg & Tadalafil 40 mg) - Part 1
Description	Cmax is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples were collected at the indicated time points for analysis of ambrisentan and tadafil. The analysis was done under fasting condition post single dose. There is no formal hypotheses tested for Part 1 of the study. The analysis was performed on Pharmacokinetic (PK) parameter population, which included all participants who provided PK parameter data.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter Population

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Ambrisentan, Cmax	766.29 (18.2)	685.33 (20.5)	738.49 (22.1)	722.57 (27.7)	755.37 (28.9)
Tadalafil, Cmax	581.41 (27.6)	595.47 (22.3)	588.11 (24.5)	590.36 (21.4)	567.62 (18.0)

2. Primary Outcome

Title	Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to Infinite (Inf) Time, AUC (0-inf) of Ambrisentan and Tadalafil in FDC (Ambrisentan 10 mg + Tadalafil 40 mg) and Montherapies (Ambrisentan 10 mg & Tadalafil 40 mg) - Part 1
Description	AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for ambrisentan and tadafil. Blood samples were collected at the indicated time-points. The analysis was done under fasting condition post single dose. There is no formal hypothesis tested for Part 1 of the study.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter Population

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Ambrisentan, (AUC 0 - inf)	5566.06 (23.8)	5556.44 (25.9)	5788.91 (25.8)	6007.57 (23.7)	5746.73 (20.8)
Tadalafil, (AUC 0 - inf)	13408.30 (41.3)	14415.47 (41.8)	14545.28 (38.4)	14418.35 (37.8)	13955.85 (36.2)

3. Primary Outcome

Title	AUC From Time of Dose to Last Measurable Concentration (AUC [0-t]), in FDC, (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fasting- Part 1
Description	AUC (0-t), was defined as, the AUC measured from the time of dose to the last measurable concentration. Blood samples of 2.7 mL and 2 mL, were collected for ambrisentan and tadafil respectively. The plasma samples at Part 1, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours. The analysis was done under fasting condition post single dose. The PK Parameter Population was used for analysis. There is no formal hypotheses tested for Part 1 of the study.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Ambrisentan, (AUC 0- t)	5418.03 (22.9)	5434.88 (25.3)	5655.75 (25.5)	5858.18 (22.9)	5605.58 (20.2)
Tadalafil, (AUC 0- t)	12469.86 (37.1)	13307.95 (37.4)	13376.86 (34.8)	13238.89 (33.4)	12805.01 (32.2)

4. Primary Outcome

Title	Cmax of Ambrisentan and Tadalafil in FDC (Ambrisentan 10 mg + Tadalafil 40 mg) and Montherapies (Ambrisentan 10 mg & Tadalafil 40 mg) - Part 2
Description	Cmax is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples were collected at the indicated time-points, of Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose. The analysis was done under fasting condition post single dose. There is no formal hypotheses tested for Part 2 of the study. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter Population

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies, ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Ambrisentan, (n=21,20,20,20)	710.90 (28.2)	720.79 (21.1)	748.63 (22.9)	726.15 (31.4)
Tadalafil, (n=20,20,20,20)	537.80 (27.6)	561.60 (28.4)	550.78 (28.6)	553.31 (20.5)

5. Primary Outcome

Title	AUC (0 - Inf) for FDC, (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fasting- Part 2
Description	AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for ambrisentan and tadafil. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 2, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis, was done under fasting condition post single dose. PK parameter Populatio was used for analysis. There is no formal hypotheses tested for Part 2 of the study. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter Population

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies, ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Ambrisentan, AUC (0-inf) (n=21,20,20,20)	6029.19 (29.6)	6179.41 (27.2)	6189.22 (29.5)	6201.40 (25.7)
Tadalafil, AUC ( 0 - inf) (n=20,20,20,20)	14006.59 (46.7)	14443.86 (44.8)	14502.37 (40.5)	14457.33 (40.5)

6. Primary Outcome

Title	AUC (0-t) for FDC, (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fasting- Part 2
Description	AUC (0-t), was defined as, the AUC measured from the time of dose to the last measurable concentration. Blood samples of 2.7 mL and 2 mL, were collected for ambrisentan and tadafil respectively. The plasma samples for Part 2, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours. The analysis was done under fasting condition post single dose. PK parameter Population was used for analysis. There is no formal hypotheses tested for Part 2 of the study. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter Population

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies, ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Ambrisentan, (n=21,20,20,20)	5893.74 (29.4)	6016.62 (27.1)	6051.83 (29.6)	6015.11 (25.9)
Tadalafil, (n=20,20,20,20)	12832.91 (39.6)	13149.19 (37.5)	13305.50 (35.2)	13275.08 (33.3)

7. Primary Outcome

Title	Cmax for Ambrisentan and Tadalafil, Following Candidate FDC (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fed and Fasted Conditions-Part 3A
Description	Cmax is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3A, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fed and fasting condition post single dose. PK parameter population was used.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Ambrisentan, Cmax	550.02 (30.9)	756.60 (24.1)	515.61 (33.4)	728.32 (29.8)
Tadalafil, Cmax	525.10 (26.5)	508.72 (24.9)	533.67 (19.5)	520.62 (21.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F3
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0667
	Confidence Interval	(2-Sided) 90%; 0.9657 to 1.1784
	Parameter Dispersion	Type: Value:
	Estimation Comments	X1 Vs R1, ambrisentan

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F2, Part 1,Treatment F4
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0353
	Confidence Interval	(2-Sided) 90%; 0.9293 to 1.1534
	Parameter Dispersion	Type: Value:
	Estimation Comments	X2 Vs R2, ambrisentan

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F3
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.9839
	Confidence Interval	(2-Sided) 90%; 0.9288 to 1.0423
	Parameter Dispersion	Type: Value:
	Estimation Comments	X1 Vs R1, tadalafil

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F2, Part 1,Treatment F4
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.9656
	Confidence Interval	(2-Sided) 90%; 0.9151 to 1.0188
	Parameter Dispersion	Type: Value:
	Estimation Comments	X2 Vs R2, tadalafil

8. Primary Outcome

Title	AUC (0-inf) for Ambrisentan and Tadalafil, Following Candidate FDC (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fed and Fasted Conditions-3A
Description	AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for ambrisentan and tadafil. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3A, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48 and 72 hours post-dose. The analysis, was done under fed and fasting conditions post single dose. PK parameter population was used.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population.

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Ambrisentan, AUC (0-inf)	6075.51 (26.1)	6231.48 (25.1)	5898.72 (27.7)	6155.60 (24.4)
Tadalafil, AUC (0-inf)	16086.66 (41.5)	14856.32 (40.0)	16596.18 (37.8)	14612.84 (41.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F3
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0300
	Confidence Interval	(2-Sided) 90%; 0.9965 to 1.0646
	Parameter Dispersion	Type: Value:
	Estimation Comments	X1 Vs R1, ambrisentan

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F2, Part 1,Treatment F4
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0141
	Confidence Interval	(2-Sided) 90%; 0.9820 to 1.0473
	Parameter Dispersion	Type: Value:
	Estimation Comments	X2 Vs R2, ambrisentan

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F3
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.9693
	Confidence Interval	(2-Sided) 90%; 0.9310 to 1.0092
	Parameter Dispersion	Type: Value:
	Estimation Comments	X1 Vs R1, tadalafil

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F2, Part 1,Treatment F4
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0157
	Confidence Interval	(2-Sided) 90%; 0.9553 to 1.0799
	Parameter Dispersion	Type: Value:
	Estimation Comments	X2 Vs R2, tadalafil

9. Primary Outcome

Title	AUC (0-t) for Ambrisentan and Tadalafil, Following Candidate FDC (Ambrisentan 10 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 10 mg & Tadalafil 40 mg), Under Fed and Fasted Conditions-Part 3A
Description	AUC (0-t), was defined as, the AUC measured from the time of dose to the last measurable concentration. Blood samples of 2.7 mL and 2 mL, were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3A, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fed and fasting condition post single dose. PK parameter population was used.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Ambrisentan, AUC (0-t)	5926.87 (25.7)	6090.74 (24.8)	5766.71 (27.4)	6012.51 (24.0)
Tadalafil, AUC (0-t)	14366.73 (33.7)	13320.79 (32.4)	14946.32 (31.1)	13114.00 (32.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F3
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0278
	Confidence Interval	(2-Sided) 90%; 0.9943 to 1.0623
	Parameter Dispersion	Type: Value:
	Estimation Comments	X1 Vs R1, ambrisentan

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F2, Part 1,Treatment F4
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0144
	Confidence Interval	(2-Sided) 90%; 0.9832 to 1.0466
	Parameter Dispersion	Type: Value:
	Estimation Comments	X2 Vs R2, ambrisentan

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F3
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.9612
	Confidence Interval	(2-Sided) 90%; 0.9265 to 0.9972
	Parameter Dispersion	Type: Value:
	Estimation Comments	X1 Vs R1, tadalafil

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F2, Part 1,Treatment F4
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3A of the study is designed to test the bioequivalence of a FDC of ambrisentan 10 mg + tadalafil 40 mg (test) relative to reference monotherapies of ambrisentan 10 mg & tadalafil 40 mg taken concurrently (reference) in healthy participants in both the fed and fasted states.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0122
	Confidence Interval	(2-Sided) 90%; 0.9562 to 1.0715
	Parameter Dispersion	Type: Value:
	Estimation Comments	X2 Vs R2, tadalafil

10. Primary Outcome

Title	Cmax for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 40 mg) Under Fasted Conditions-3B
Description	Cmax is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fasting condition post single dose.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment R3
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.
Measure Participants	30	31
Ambrisentan, Cmax	375.87 (23.0)	380.47 (26.2)
Tadalafil, Cmax	488.36 (19.7)	511.80 (28.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0153
	Confidence Interval	(2-Sided) 90%; 0.9348 to 1.1027
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y1 Vs R3, ambrisentan

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.9758
	Confidence Interval	(2-Sided) 90%; 0.9044 to 1.0529
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y1 Vs R3, tadalafil

11. Primary Outcome

Title	AUC (0-inf) for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 40 mg) Under Fasted Conditions-3B
Description	AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for ambrisentan and tadafil. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36,48 and 72 hours post-dose. The analysis was done under fasting condition post single dose. PK Parameter Population was used for analysis.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment R3
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.
Measure Participants	30	31
Ambrisentan AUC (0-inf)	3397.51 (19.7)	3277.81 (20.8)
Tadalafil, AUC (0-inf)	14724.34 (39.7)	14938.29 (40.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0390
	Confidence Interval	(2-Sided) 90%; 1.0168 to 1.0617
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y1 Vs R3, ambrisentan

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.9806
	Confidence Interval	(2-Sided) 90%; 0.9106 to 1.0560
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y1 Vs R3, tadalafil

12. Primary Outcome

Title	AUC (0-t) for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 40 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 40 mg) Under Fasted Conditions-3B
Description	AUC (0-t), was defined as, the AUC measured from the time of dose to the last measurable concentration. Blood samples of 2.7 mL and 2 mL, were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fasting condition post single dose. PK parameter population was used for analysis.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter population

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment R3
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.
Measure Participants	30	31
Ambrisentan, AUC (0-t)	3297.16 (19.8)	3190.51 (20.3)
Tadalafil, AUC (0-t)	13119.89 (31.0)	13325.63 (35.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0365
	Confidence Interval	(2-Sided) 90%; 1.0138 to 1.0596
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y1 Vs R3, ambrisentan

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.9821
	Confidence Interval	(2-Sided) 90%; 0.9145 to 1.0547
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y1 Vs R3, tadalafil

13. Primary Outcome

Title	Cmax for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 20 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 20 mg) Under Fasted Conditions-3B
Description	Cmax is defined as the maximum (or peak) plasma concentration that the drug achieves, after the drug has been administered. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fasting condition post single dose. PK parameter population was used.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter population

Arm/Group Title	Part 3B,Treatment Y2	Part 3B,Treatment R4
Arm/Group Description	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	31	30
Ambrisentan, Cmax	405.89 (25.1)	358.89 (24.5)
Tadalafil, Cmax	340.63 (23.1)	303.74 (22.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.1176
	Confidence Interval	(2-Sided) 90%; 1.0166 to 1.2287
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y2 Vs R4, ambrisentan

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.1196
	Confidence Interval	(2-Sided) 90%; 1.0429 to 1.2019
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y2 Vs R4, tadalafil

14. Primary Outcome

Title	AUC (0-inf) for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 20 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 20 mg) Under Fasted Conditions-3B
Description	AUC (0- inf), is defined as area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for ambrisentan and tadafil. Blood samples of 2.7 mL and 2 mL were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis, was done under fasting conditions post single dose. PK parameter population was used for analysis.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Parameter Population.

Arm/Group Title	Part 3B,Treatment Y2	Part 3B,Treatment R4
Arm/Group Description	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	31	30
Ambrisentan AUC (0-inf)	3347.76 (20.9)	3205.51 (20.6)
Tadalafil, AUC (0-inf)	7962.14 (32.2)	7748.47 (32.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0353
	Confidence Interval	(2-Sided) 90%; 1.0009 to 1.0710
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y2 Vs R4, ambrisentan

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0362
	Confidence Interval	(2-Sided) 90%; 0.9910 to 1.0834
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y2 Vs R4, tadalafil

15. Primary Outcome

Title	AUC (0-t) for Ambrisentan and Tadalafil, FDCs (Ambrisentan 5 mg + Tadalafil 20 mg) Relative to Reference Monotherapies Tested (Ambrisentan 5 mg & Tadalafil 20 mg) Under Fasted Conditions- Part 3B
Description	AUC (0-t), was defined as, the AUC measured from the time of dose to the last measurable concentration. Blood samples of 2.7 mL and 2 mL, were collected for ambrisentan and tadafil respectively. The plasma samples for Part 3B, were collected at the time-points pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48 and 72 hours post-dose. The analysis was done under fasting condition post single dose. PK parameter population was used for analysis.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter population

Arm/Group Title	Part 3B,Treatment Y2	Part 3B,Treatment R4
Arm/Group Description	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	31	30
Ambrisentan AUC (0-t)	3254.70 (21.0)	3116.10 (20.3)
Tadalafil, AUC (0-t)	7264.28 (26.6)	7076.48 (27.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0351
	Confidence Interval	(2-Sided) 90%; 1.0002 to 1.0713
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y2 Vs R4, ambrisentan

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1,Treatment F1, Part 1,Treatment F2
	Comments
	Type of Statistical Test	Equivalence
	Comments	Part 3B of the study is set to establish bioequivalence between the Fixed Dose Combination of an additional two dose strengths (ambrisentan 5 mg + tadalafil 40 mg and ambrisentan 5 mg + tadalafil 20 mg).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.0324
	Confidence Interval	(2-Sided) 90%; 0.9929 to 1.0734
	Parameter Dispersion	Type: Value:
	Estimation Comments	Y2 Vs R4, tadalafil

16. Secondary Outcome

Title	Time Taken to Reach Maximum Concentration (Tmax) for Ambrisentan and Tadalafil in FDC and Reference Treatment - Part 1
Description	Serial blood samples were collected at the indicated time-points. In Part 3A, tmax was determined for ambrisentan and tadalafil when administered in FDC (10mg/40mg) under fed state and fasted state and as reference monotherapies (ambrisentan 10 mg and tadalafil 40 mg). PK parameter population was used to measure the tmax.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter Population.

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Ambrisentan, Tmax	1.000	1.500	1.500	1.500	1.500
Tadafil, Tmax	1.500	2.000	2.000	2.000	1.500

17. Secondary Outcome

Title	Time Taken to Reach Maximum Concentration (Tmax) for Ambrisentan and Tadalafil in FDC and Reference Treatment - Part 2
Description	Serial blood samples were collected at the indicated time-points. In Part 3A, tmax was determined for ambrisentan and tadalafil when administered in FDC (10mg/40mg) under fed state and fasted state and as reference monotherapies (ambrisentan 10 mg and tadalafil 40 mg). PK parameter population was used to measure the tmax. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter population.

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies, ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Ambrisentan, Tmax (n=21,20,20,20)	1.500	1.500	1.500	1.508
Tadafil, Tmax (n=20,20,20,20)	2.017	1.750	2.000	2.000

18. Secondary Outcome

Title	Time Taken to Reach Maximum Concentration (Tmax) for Ambrisentan and Tadalafil in FDC and Reference Treatment - Part 3A
Description	Serial blood samples were collected at the indicated time-points. In Part 3A, tmax was determined for ambrisentan and tadalafil when administered in FDC (10mg/40mg) under fed state and fasted state and as reference monotherapies (ambrisentan 10 mg and tadalafil 40 mg). PK parameter population was used to measure the tmax.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter Population.

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, , the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Ambrisentan, Tmax	4.00	1.500	4.00	2.000
Tadafil, Tmax	8.000	2.500	8.000	2.258

19. Secondary Outcome

Title	Time Taken to Reach Maximum Concentration (Tmax) for Ambrisentan and Tadalafil in FDC and Reference Treatment - Part 3B
Description	Serial blood samples were collected at the indicated time-points. In Part 3B, tmax was determined for ambrisentan and tadalafil when administered in FDC (10mg/40mg) under fed state and fasted state and as reference monotherapies (ambrisentan 10 mg and tadalafil 40 mg). PK parameter population was used to measure the tmax.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter Population.

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	31	30
Ambrisentan, Tmax	1.767	1.500	2.000	1.758
Tadafil, Tmax	2.500	1.500	2.500	2.008

20. Secondary Outcome

Title	Plasma Half Life (t1/2) for Ambrisentan and Tadalafil in FDC and Reference Treatment Under Fed and Fasted Condition- Part1
Description	t1/2 is defined as the time required by the concentration of the drug to reach half of its original value.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter Population.

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg Sodium laurilsulfate (SLS), with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Ambrisentan, t1/2	16.74 (18.2)	15.25 (19.2)	15.76 (17.3)	15.25 (20.0)	16.08 (17.9)
Tadalafil, t1/2	17.08 (30.4)	17.76 (33.3)	18.38 (33.3)	18.48 (33.0)	18.04 (30.4)

21. Secondary Outcome

Title	Plasma t1/2 for Ambrisentan and Tadalafil in FDC and Reference Treatment Under Fed and Fasted Condition- Part 2
Description	t1/2 is defined as the time required by the concentration of the drug to reach half of its original value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter Population.

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Ambrisentan, t1/2 (n=21,20,20,20)	15.19 (24.5)	15.76 (33.3)	15.39 (18.6)	16.60 (34.4)
Tadalafil, t1/2, (n=20,20,20,20)	18.58 (30.6)	18.63 (33.2)	18.22 (33.2)	17.98 (32.6)

22. Secondary Outcome

Title	Plasma t1/2 for Ambrisentan and Tadalafil in FDC and Reference Treatment Under Fed and Fasted Condition- Part 3A
Description	t1/2 is defined as the time required by the concentration of the drug to reach half of its original value. The serial blood samples were assessed at specified timepoints.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter population

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, , the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Ambrisentan, t1/2	15.65 (16.7)	15.42 (15.9)	14.66 (13.7)	15.63 (16.6)
Tadalafil, t1/2	20.09 (34.4)	19.85 (34.2)	19.29 (33.4)	19.86 (36.8)

23. Secondary Outcome

Title	Plasma t1/2 for Ambrisentan and Tadalafil in FDC and Reference Treatment Under Fed and Fasted Condition- Part 3B
Description	t1/2 is defined as the time required by the concentration of the drug to reach half of its original value. The serial blood samples were assessed at specified timepoints.
Time Frame	Pre-dose, 0.5 hours, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 36, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

PK parameter Population.

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	31	30
Ambrisentan, t1/2	16.39 (21.6)	16.42 (17.1)	16.15 (18.7)	16.00 (19.7)
Tadalafil, t1/2	20.27 (34.3)	19.01 (31.1)	20.34 (34.4)	18.95 (30.8)

24. Secondary Outcome

Title	Change From Baseline in Vital- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), Part 1
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for SBP and DBP. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1. Safety population included all the participants enrolled into the study who received atleast one dose of investigational product.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
DBP, 0.5 hour	-3.33 (6.626)	-3.54 (4.164)	-4.20 (5.622)	-2.86 (5.330)	-2.79 (7.737)
DBP, 1 hour	-5.33 (6.516)	-4.72 (4.008)	-5.63 (3.938)	-5.73 (6.001)	-4.40 (4.705)
DBP, 2 hour	-5.24 (7.118)	-5.28 (5.220)	-5.98 (3.632)	-7.27 (5.101)	-5.83 (4.856)
DBP, 4 hour	-4.29 (5.205)	-5.72 (4.064)	-6.07 (6.031)	-7.09 (5.149)	-5.21 (6.059)
DBP, 8 hour	-9.10 (9.963)	-6.67 (6.704)	-6.50 (5.610)	-9.68 (6.263)	-7.83 (6.487)
DBP, 12 hour	-4.76 (7.604)	-6.16 (5.685)	-5.72 (5.994)	-8.18 (8.296)	-5.60 (7.687)
DBP, 24 hour	-5.86 (7.004)	-4.50 (6.308)	-4.07 (5.792)	-5.59 (6.235)	-3.55 (5.987)
DBP, 48 hour	-2.38 (5.232)	-1.02 (6.091)	-4.02 (6.589)	-4.18 (4.382)	-0.74 (6.644)
DBP, 72 hour	0.76 (5.845)	-0.67 (5.676)	0.20 (7.371)	-1.73 (5.311)	-0.15 (6.556)
SBP, 0.5 hour	-1.10 (7.521)	-3.22 (8.590)	-1.59 (5.441)	-3.68 (6.438)	-3.36 (4.953)
SBP, 1 hour	-2.76 (8.153)	-4.13 (7.091)	-2.54 (7.662)	-6.00 (7.624)	-3.74 (6.549)
SBP, 2 hour	-6.05 (9.822)	-5.39 (7.116)	-3.11 (6.098)	-6.91 (9.148)	-5.40 (4.543)
SBP, 4 hour	-3.90 (7.143)	-7.30 (8.244)	-5.50 (5.671)	-6.59 (7.699)	-5.36 (7.892)
SBP, 8 hour	-6.10 (8.770)	-5.48 (9.279)	-4.02 (7.346)	-10.55 (9.579)	-8.40 (8.434)
SBP, 12 hour	0.14 (8.755)	-0.84 (9.278)	0.54 (9.720)	-4.77 (12.023)	-3.60 (8.185)
SBP, 24 hour	-1.48 (6.541)	-3.17 (9.767)	0.02 (7.770)	-3.82 (7.276)	-1.79 (6.758)
SBP, 48 hour	1.52 (9.052)	2.39 (7.010)	2.50 (8.577)	-0.64 (7.315)	-0.31 (8.710)
SBP, 72 hour	6.95 (7.048)	3.52 (8.993)	3.37 (8.801)	4.18 (7.341)	3.00 (7.854)

25. Secondary Outcome

Title	Change From Baseline in Vital Signs-Heart Rate, Part 1
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Heart rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	20	20	20	21
HR, 0.5 hour	2.98 (4.766)	2.89 (2.558)	1.13 (3.181)	2.98 (3.718)	3.74 (4.024)
HR, 1 hour	3.79 (4.314)	4.11 (2.620)	2.48 (4.981)	3.30 (3.112)	4.17 (4.223)
HR, 2 hour	3.69 (5.451)	4.41 (3.107)	1.91 (4.562)	2.48 (4.393)	2.83 (4.127)
HR, 4 hour	3.26 (4.449)	3.63 (3.331)	1.52 (4.636)	3.16 (5.176)	2.12 (3.584)
HR, 8 hour	8.26 (6.488)	7.93 (5.407)	7.17 (6.583)	6.11 (5.323)	7.55 (5.522)
HR, 12 hour	10.40 (6.387)	12.75 (6.141)	10.48 (7.264)	11.11 (7.687)	10.83 (5.342)
HR, 24 hour	6.17 (4.498)	7.02 (6.343)	6.52 (5.371)	5.61 (5.381)	6.74 (7.915)
HR, 48 hour	9.21 (5.110)	8.67 (6.539)	7.57 (5.623)	6.48 (5.302)	7.69 (5.501)
HR, 72 hour	6.21 (4.665)	7.54 (7.762)	6.57 (7.789)	5.57 (7.323)	5.03 (6.014)

26. Secondary Outcome

Title	Change From Baseline in Vital- Temperature, Part 1
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for temperature. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Temperature, 0.5 hour	-0.20 (0.220)	-0.05 (0.250)	-0.12 (0.233)	-0.18 (0.357)	-0.03 (0.201)
Temperature, 1 hour	-0.15 (0.275)	-0.09 (0.343)	-0.07 (0.216)	-0.06 (0.426)	-0.12 (0.386)
Temperature, 2 hour	-0.14 (0.271)	-0.16 (0.383)	-0.23 (0.392)	-0.04 (0.473)	-0.14 (0.393)
Temperature, 4 hour	-0.28 (0.363)	-0.08 (0.326)	-0.17 (0.328)	-0.03 (0.331)	-0.10 (0.381)
Temperature, 8 hour	-0.04 (0.460)	0.03 (0.438)	-0.08 (0.400)	0.08 (0.422)	0.02 (0.408)
Temperature, 12 hour	0.09 (0.371)	0.16 (0.386)	-0.03 (0.438)	0.08 (0.405)	0.02 (0.597)
Temperature, 24 hour	-0.04 (0.273)	0.03 (0.328)	0.14 (0.390)	0.13 (0.413)	0.07 (0.543)
Temperature, 48 hour	-0.01 (0.371)	0.18 (0.404)	0.01 (0.393)	0.05 (0.571)	0.16 (0.508)
Temperature, 72 hour	0.12 (0.351)	0.03 (0.503)	-0.02 (0.392)	0.10 (0.424)	0.02 (0.506)

27. Secondary Outcome

Title	Change From Baseline in Vital Signs-Respiratory Rate, Part 1
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Respiratory rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	20	20	20	21
Respiratory rate, 0.5 hour	-0.5 (2.23)	-0.7 (2.38)	-0.1 (3.17)	0.3 (1.88)	1.1 (1.49)
Respiratory rate, 1 hour	-0.5 (2.62)	-1.0 (2.69)	0.0 (2.76)	0.6 (2.72)	0.6 (2.11)
Respiratory rate, 2 hour	-0.0 (1.56)	-1.0 (2.08)	-0.2 (2.55)	0.4 (2.48)	0.5 (2.44)
Respiratory rate, 4 hour	-1.0 (2.10)	-0.8 (1.98)	-0.5 (2.91)	0.2 (2.54)	0.4 (2.42)
Respiratory rate, 8 hour	0.1 (2.73)	0.2 (2.33)	0.0 (2.63)	0.6 (2.42)	0.6 (2.20)
Respiratory rate, 12 hour	0.5 (2.86)	0.4 (1.81)	0.3 (2.93)	0.9 (2.94)	1.7 (3.30)
Respiratory rate, 24 hour	-0.5 (2.44)	-0.7 (2.22)	-0.4 (2.63)	-0.1 (2.35)	1.0 (3.20)
Respiratory rate, 48 hour	0.2 (2.68)	-0.6 (2.52)	0.4 (3.07)	-0.0 (2.55)	0.3 (3.86)
Respiratory rate, 72 hour	-0.8 (2.44)	-0.1 (3.38)	0.7 (3.17)	1.0 (2.60)	0.8 (2.46)

28. Secondary Outcome

Title	Change From Baseline in Vital- SBP and DBP, Part 2
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for SBP and DBP. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
DBP, 0.5 hour	-2.29 (5.396)	0.28 (5.707)	-0.25 (5.564)	-1.00 (5.091)
DBP, 1 hour	-4.71 (7.329)	-4.23 (5.686)	-4.55 (5.264)	-4.35 (5.703)
DBP, 2 hour	-5.67 (7.073)	-4.98 (5.488)	-5.85 (5.974)	-7.05 (5.954)
DBP, 4 hour	-4.10 (6.468)	-3.53 (7.159)	-3.90 (7.080)	-5.10 (6.131)
DBP, 8 hour	-4.43 (8.603)	-2.58 (7.979)	-5.15 (6.917)	-5.65 (8.278)
DBP, 12 hour	-3.76 (7.800)	-3.18 (5.669)	-2.25 (6.084)	-4.35 (5.912)
DBP, 24 hour	-3.00 (7.342)	-1.03 (6.791)	-2.00 (6.318)	-5.25 (6.470)
DBP, 48 hour	-3.29 (7.125)	2.48 (6.451)	1.35 (5.956)	1.40 (4.901)
DBP, 72 hour	0.95 (8.399)	3.23 (5.357)	2.05 (6.671)	1.50 (6.907)
SBP, 0.5 hour	-1.57 (5.388)	1.63 (5.314)	2.90 (4.576)	-0.33 (4.913)
SBP, 1 hour	-4.43 (8.996)	-3.93 (6.057)	-2.05 (8.000)	-1.98 (7.144)
SBP, 2 hour	-5.52 (8.848)	-2.48 (5.683)	-1.45 (7.112)	-7.33 (9.574)
SBP, 4 hour	-3.05 (7.561)	-2.13 (6.456)	-2.45 (7.082)	-5.58 (6.053)
SBP, 8 hour	-5.43 (8.982)	-3.98 (7.046)	-2.35 (6.471)	-6.38 (8.617)
SBP, 12 hour	-0.05 (7.292)	4.38 (9.418)	2.00 (6.951)	0.83 (6.822)
SBP, 24 hour	-2.95 (7.847)	-0.68 (8.307)	-0.30 (8.163)	-1.68 (6.218)
SBP, 48 hour	-2.00 (5.820)	4.78 (7.911)	0.85 (8.570)	2.08 (4.660)
SBP, 72 hour	4.14 (7.636)	5.13 (7.609)	5.00 (6.345)	3.48 (8.367)

29. Secondary Outcome

Title	Change From Baseline in Vital Signs-Heart Rate, Part 2
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Heart rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1. Safety population included all the participants enrolled into the study who received atleast one dose of investigational product.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
HR, 0.5 hour	1.45 (4.040)	2.85 (4.934)	1.95 (6.219)	2.20 (3.975)
HR, 1 hour	3.12 (4.475)	3.85 (4.665)	5.10 (6.528)	5.35 (3.208)
HR, 2 hour	3.21 (3.720)	3.75 (6.568)	2.75 (5.959)	6.45 (6.039)
HR, 4 hour	3.36 (5.287)	5.45 (11.978)	3.20 (7.428)	6.00 (5.978)
HR, 8 hour	9.36 (7.720)	8.30 (7.596)	6.55 (6.901)	8.30 (9.234)
HR, 12 hour	17.21 (7.348)	14.80 (9.512)	15.50 (6.473)	16.45 (6.669)
HR, 24 hour	6.74 (6.100)	8.80 (6.031)	8.00 (7.395)	8.70 (7.388)
HR, 48 hour	6.79 (5.361)	5.70 (4.697)	5.10 (5.973)	5.90 (4.599)
HR, 72 hour	9.40 (8.412)	7.90 (8.534)	7.80 (8.427)	9.30 (7.153)

30. Secondary Outcome

Title	Change From Baseline in Vital- Temperature, Part 2
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for temperature. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1. Safety population included all the participants enrolled into the study who received atleast one dose of investigational product.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Temperature, 0.5 hour	-0.07 (0.403)	-0.02 (0.281)	-0.05 (0.261)	-0.14 (0.339)
Temperature, 1 hour	-0.13 (0.280)	-0.11 (0.301)	-0.01 (0.300)	-0.04 (0.342)
Temperature, 2 hour	-0.12 (0.349)	-0.17 (0.279)	-0.03 (0.310)	-0.23 (0.397)
Temperature, 4 hour	-0.01 (0.348)	-0.06 (0.366)	0.03 (0.286)	-0.19 (0.399)
Temperature, 8 hour	0.02 (0.397)	-0.08 (0.375)	0.05 (0.343)	0.03 (0.425)
Temperature, 12 hour	0.20 (0.409)	0.04 (0.437)	0.09 (0.418)	0.10 (0.494)
Temperature, 24 hour	-0.06 (0.285)	-0.02 (0.373)	0.24 (0.298)	0.07 (0.400)
Temperature, 48 hour	-0.06 (0.441)	-0.06 (0.312)	0.03 (0.353)	-0.11 (0.488)
Temperature, 72 hour	-0.09 (0.435)	-0.13 (0.490)	0.05 (0.375)	0.06 (0.366)

31. Secondary Outcome

Title	Change From Baseline in Vital Signs-Respiratory Rate, Part 2
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Respiratory rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Respiratory rate, 0.5 hour	0.7 (2.92)	-0.7 (2.27)	0.3 (2.85)	-1.1 (2.04)
Respiratory rate, 1 hour	-0.9 (2.15)	-0.4 (2.56)	0.3 (2.70)	-0.7 (2.21)
Respiratory rate, 2 hour	-0.6 (3.32)	-1.2 (2.86)	0.4 (3.41)	-1.1 (2.70)
Respiratory rate, 4 hour	-0.1 (2.87)	-0.1 (3.34)	-0.1 (3.21)	-1.0 (2.50)
Respiratory rate, 8 hour	0.1 (3.00)	0.5 (2.82)	0.4 (2.37)	-0.5 (2.06)
Respiratory rate, 12 hour	0.8 (2.93)	0.2 (2.46)	0.8 (2.61)	-0.5 (2.87)
Respiratory rate, 24 hour	-0.1 (3.00)	-0.3 (2.92)	1.3 (2.70)	0.4 (2.32)
Respiratory rate, 48 hour	-0.5 (2.60)	-0.2 (2.14)	0.7 (2.62)	-0.6 (2.24)
Respiratory rate, 72 hour	0.2 (2.79)	0.6 (2.67)	0.6 (2.91)	0.6 (2.82)

32. Secondary Outcome

Title	Change From Baseline in Vital- SBP and DBP, Part 3A
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for SBP, DBP. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, , the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
DBP, 0.5 hour	-3.47 (6.724)	-0.36 (5.821)	-3.02 (7.779)	-1.45 (6.943)
DBP, 1 hour	-6.69 (6.509)	-4.73 (6.418)	-5.86 (7.055)	-5.36 (7.768)
DBP, 2 hour	-8.97 (7.104)	-6.03 (5.840)	-6.89 (6.173)	-6.05 (7.745)
DBP, 4 hour	-8.75 (5.879)	-6.24 (6.148)	-10.30 (6.722)	-6.27 (7.799)
DBP, 8 hour	-8.41 (7.088)	-7.76 (8.100)	-6.45 (8.865)	-8.20 (8.845)
DBP, 12 hour	-7.25 (7.097)	-6.18 (8.080)	-7.67 (8.274)	-7.36 (9.886)
DBP, 24 hour	-7.25 (7.033)	-4.27 (6.011)	-4.77 (7.168)	-5.89 (6.847)
DBP, 48 hour	-2.41 (9.414)	-0.79 (7.730)	-1.89 (6.945)	-1.77 (7.503)
DBP, 72 hour	-1.56 (6.361)	1.24 (6.544)	-1.52 (9.187)	0.80 (9.118)
SBP, 0.5 hour	5.75 (5.236)	-0.32 (8.074)	4.55 (8.543)	0.17 (5.822)
SBP, 1 hour	2.88 (7.478)	-4.14 (9.772)	2.86 (9.186)	-1.95 (5.959)
SBP, 2 hour	0.28 (9.549)	-2.05 (8.873)	-0.08 (7.294)	-3.95 (6.990)
SBP, 4 hour	-1.72 (7.699)	-4.35 (9.423)	-4.30 (8.270)	-4.77 (7.717)
SBP, 8 hour	-5.06 (9.313)	-5.32 (10.608)	-5.23 (9.288)	-5.27 (7.975)
SBP, 12 hour	-0.03 (8.372)	-0.47 (10.702)	-1.05 (9.116)	-1.58 (9.155)
SBP, 24 hour	-0.78 (8.974)	-1.08 (10.400)	-2.48 (6.478)	-2.08 (7.106)
SBP, 48 hour	2.72 (8.437)	1.68 (9.134)	1.36 (7.927)	0.80 (7.661)
SBP, 72 hour	1.81 (8.538)	3.14 (11.277)	3.86 (11.332)	3.52 (6.752)

33. Secondary Outcome

Title	Change From Baseline in Vital Signs-Heart Rate, Part 3A
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Heart rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, , the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
HR, 0.5 hour	8.28 (5.785)	2.64 (3.900)	10.66 (4.717)	2.81 (4.156)
HR, 1 hour	10.28 (6.108)	5.52 (4.154)	12.97 (6.573)	4.66 (3.897)
HR, 2 hour	11.06 (5.891)	4.61 (4.565)	11.41 (6.439)	4.16 (4.306)
HR, 4 hour	10.16 (6.491)	5.06 (6.910)	10.91 (5.431)	4.44 (4.629)
HR, 8 hour	9.06 (5.872)	10.79 (7.847)	10.16 (7.407)	8.56 (6.624)
HR, 12 hour	15.28 (10.232)	15.91 (9.669)	14.38 (10.204)	16.38 (8.917)
HR, 24 hour	8.72 (5.341)	8.73 (7.048)	7.00 (6.673)	7.28 (4.704)
HR, 48 hour	8.50 (4.465)	9.45 (7.527)	9.47 (7.301)	8.03 (5.290)
HR, 72 hour	9.19 (6.708)	10.91 (10.476)	9.59 (9.088)	10.03 (8.041)

34. Secondary Outcome

Title	Change From Baseline in Vital- Temperature, Part 3A
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for temperature. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Temperature, 0.5 hour	0.21 (0.288)	0.01 (0.344)	0.15 (0.306)	0.12 (0.303)
Temperature, 1 hour	0.18 (0.252)	0.07 (0.315)	0.12 (0.262)	0.04 (0.282)
Temperature, 2 hour	0.26 (0.278)	0.05 (0.268)	0.10 (0.244)	0.07 (0.317)
Temperature, 4 hour	0.18 (0.352)	0.15 (0.299)	0.16 (0.305)	-0.01 (0.402)
Temperature, 8 hour	0.21 (0.450)	0.12 (0.425)	0.15 (0.409)	0.15 (0.504)
Temperature, 12 hour	0.22 (0.409)	0.27 (0.392)	0.09 (0.366)	0.27 (0.492)
Temperature, 24 hour	0.29 (0.429)	0.25 (0.351)	0.06 (0.332)	0.16 (0.362)
Temperature, 48 hour	0.34 (0.713)	0.28 (0.473)	0.12 (0.358)	0.32 (0.327)
Temperature, 72 hour	0.18 (0.414)	0.20 (0.334)	0.10 (0.418)	0.18 (0.520)

35. Secondary Outcome

Title	Change From Baseline in Vital Signs-Respiratory Rate, Part 3A
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Respiratory rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, , the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Respiratory rate, 0.5 hour	0.4 (2.51)	0.8 (1.95)	1.5 (2.66)	-0.2 (2.46)
Respiratory rate, 1 hour	0.9 (2.83)	0.2 (2.57)	0.8 (2.26)	-0.7 (2.13)
Respiratory rate, 2 hour	0.7 (2.72)	0.7 (2.59)	0.6 (2.30)	0.2 (2.89)
Respiratory rate, 4 hour	0.6 (2.76)	0.2 (2.21)	1.1 (2.59)	0.1 (2.31)
Respiratory rate, 8 hour	0.1 (2.85)	0.1 (2.15)	0.5 (2.49)	-0.3 (2.04)
Respiratory rate, 12 hour	0.9 (3.21)	0.5 (2.33)	0.6 (2.97)	0.4 (3.11)
Respiratory rate, 24 hour	-0.5 (3.14)	0.1 (2.26)	0.2 (2.75)	-1.3 (2.58)
Respiratory rate, 48 hour	0.0 (2.03)	-0.1 (2.45)	0.6 (2.93)	-0.7 (2.07)
Respiratory rate, 72 hour	0.6 (2.79)	0.3 (3.05)	0.8 (1.96)	0.1 (2.59)

36. Secondary Outcome

Title	Change From Baseline in Vital- SBP and DBP, Part 3B
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for SBP and DBP. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	32	30
DBP, 0.5 hour	-1.42 (6.365)	-2.15 (6.582)	-2.53 (5.507)	-1.53 (6.965)
DBP, 1 hour	-3.92 (6.443)	-3.31 (5.569)	-3.41 (7.157)	-3.73 (6.027)
DBP, 2 hour	-6.52 (10.758)	-5.92 (6.044)	-5.00 (5.651)	-5.70 (5.842)
DBP, 4 hour	-5.02 (4.481)	-6.85 (5.455)	-6.56 (6.488)	-6.80 (6.884)
DBP, 8 hour	-4.38 (8.616)	-6.56 (5.815)	-7.81 (6.258)	-7.23 (9.095)
DBP, 12 hour	-3.38 (8.189)	-5.15 (6.431)	-5.88 (6.644)	-7.57 (6.494)
DBP, 24 hour	-1.62 (6.464)	-4.05 (6.571)	-3.31 (5.118)	-4.90 (5.636)
DBP, 48 hour	-0.65 (7.945)	-0.40 (6.512)	-0.41 (5.491)	-1.50 (7.405)
DBP, 72 hour	0.85 (7.594)	0.31 (4.790)	-0.47 (6.074)	-0.93 (6.781)
SBP, 0.5 hour	0.77 (9.323)	-0.92 (8.734)	0.30 (8.287)	0.43 (5.157)
SBP, 1 hour	-1.27 (8.463)	0.11 (8.945)	-0.20 (7.893)	0.17 (6.823)
SBP, 2 hour	-0.57 (9.657)	-4.34 (10.254)	-1.98 (7.925)	-1.10 (4.845)
SBP, 4 hour	-4.17 (8.680)	-3.92 (7.959)	-3.14 (5.501)	-5.60 (7.831)
SBP, 8 hour	-2.87 (10.059)	-2.95 (11.644)	-3.05 (8.804)	-5.03 (7.294)
SBP, 12 hour	2.17 (11.075)	0.11 (13.298)	0.45 (7.846)	-1.03 (10.562)
SBP, 24 hour	-0.13 (8.805)	-2.56 (8.996)	0.36 (5.210)	-1.77 (8.458)
SBP, 48 hour	5.33 (8.963)	0.50 (8.748)	3.45 (6.139)	1.87 (8.345)
SBP, 72 hour	2.80 (9.174)	1.76 (8.922)	2.76 (7.236)	1.70 (9.502)

37. Secondary Outcome

Title	Change From Baseline in Vital Signs-Heart Rate, Part 3B
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for HR. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	32	30
HR, 0.5 hour	3.05 (5.103)	3.50 (4.911)	2.61 (4.652)	2.78 (4.928)
HR, 1 hour	6.05 (5.784)	4.92 (5.496)	5.70 (4.621)	5.48 (7.515)
HR, 2 hour	6.08 (5.706)	3.76 (5.524)	5.67 (4.148)	5.58 (7.157)
HR, 4 hour	4.85 (6.498)	3.69 (7.253)	4.95 (5.564)	6.22 (4.836)
HR, 8 hour	9.65 (8.102)	7.34 (6.462)	7.23 (6.453)	8.78 (8.137)
HR, 12 hour	15.85 (9.232)	15.50 (6.925)	13.89 (7.574)	16.62 (7.800)
HR, 24 hour	8.02 (6.086)	6.92 (6.162)	7.77 (6.677)	7.72 (5.700)
HR, 48 hour	9.72 (5.845)	8.18 (6.657)	8.08 (6.610)	10.15 (9.207)
HR, 72 hour	10.78 (8.397)	9.18 (7.853)	7.37 (7.256)	9.62 (7.245)

38. Secondary Outcome

Title	Change From Baseline in Vital- Temperature, Part 3B
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for temperature. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	32	30
Temperature, 0.5 hour (n=30,31,32,30)	0.06 (0.239)	0.13 (0.329)	0.11 (0.404)	0.05 (0.256)
Temperature, 1 hour (n=30,31,32,30)	0.06 (0.275)	0.07 (0.290)	0.10 (0.330)	0.09 (0.291)
Temperature, 2 hour (n=29,31,32,30)	0.05 (0.341)	0.07 (0.330)	0.09 (0.316)	0.04 (0.233)
Temperature, 4 hour(n=30,31,32,30)	0.10 (0.371)	0.05 (0.385)	0.07 (0.430)	0.09 (0.275)
Temperature, 8 hour (n=30,31,32,30)	0.29 (0.497)	0.22 (0.419)	0.23 (0.456)	0.17 (0.502)
Temperature, 12 hour (n=30,31,32,30)	0.31 (0.470)	0.39 (0.358)	0.32 (0.463)	0.45 (0.425)
Temperature, 24 hour (n=30,31,32,30)	0.34 (0.347)	0.12 (0.453)	0.23 (0.352)	0.19 (0.420)
Temperature, 48 hour (n=30,31,32,30)	0.19 (0.448)	0.13 (0.424)	0.16 (0.456)	0.22 (0.444)
Temperature, 72 hour (n=30,31,31,30)	0.33 (0.422)	0.26 (0.446)	0.14 (0.450)	0.08 (0.377)

39. Secondary Outcome

Title	Change From Baseline in Vital Signs-Respiratory Rate, Part 3-B
Description	Vital signs were measured in semi-supine position after 5 minutes rest and were assessed for Respiratory rate. Change from Baseline, was defined as value at post-Baseline visit minus the Baseline value. Baseline, was defined as Day 1.
Time Frame	Baseline and Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	32	30
Respiratory rate, 0.5 hour (n=30,31,32,30)	-0.3 (2.78)	0.4 (2.99)	-0.8 (3.08)	0.8 (3.06)
Respiratory rate, 1 hour (n=30,31,32,30)	-0.6 (2.88)	-0.7 (3.08)	-0.1 (2.98)	0.2 (2.06)
Respiratory rate, 2 hour (n=30,31,32,30)	-0.2 (2.93)	0.6 (3.64)	-0.1 (3.20)	0.6 (2.31)
Respiratory rate, 4 hour (n=30,31,32,30)	0.3 (2.68)	0.1 (3.47)	-0.4 (2.85)	0.5 (2.76)
Respiratory rate, 8 hour(n=30,31,32,30)	0.4 (2.50)	0.9 (3.31)	0.0 (3.41)	0.5 (2.75)
Respiratory rate, 12 hour (n=30,31,32,30)	-0.8 (2.67)	-0.3 (2.82)	0.2 (2.96)	1.1 (2.89)
Respiratory rate, 24 hour(n=30,31,32,30)	-1.3 (3.29)	-0.7 (3.08)	-0.6 (2.50)	0.1 (3.04)
Respiratory rate, 48 hour(n=30,31,32,30)	-0.8 (2.81)	-0.0 (3.35)	-0.1 (3.15)	1.2 (3.09)
Respiratory rate, 72 hour (n=30,31,31,30)	-0.1 (3.73)	-0.0 (2.95)	0.2 (2.89)	0.6 (2.85)

40. Secondary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings, -Part 1
Description	12-lead ECG, was measured in semi-supine position after 5 minutes rest. The data for worst case post-baseline has been reported. Data values for the participants with abnormal clinically significant values are reported. Safety population was used for analysis.
Time Frame	Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

41. Secondary Outcome

Title	Number of Participants With Abnormal ECG Findings, -Part 2
Description	12-lead ECG, were measured in semi-supine position after 5 minutes rest. It was conducted as triplicate at screen and baseline, whereas single measure at other times, unless out of range then triplicates were performed. The data for worst case post-baseline has been reported. Data values for the participants with abnormal clinically significant values are reported. Safety population was used for analysis.
Time Frame	Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Number [Participants]	0 0%	0 0%	0 0%	0 0%

42. Secondary Outcome

Title	Number of Participants With Abnormal ECG Findings, -Part 3A
Description	12-lead ECG, were measured in semi-supine position after 5 minutes rest. It was conducted as triplicate at screen and baseline, whereas single measure at other times, unless out of range then triplicates were performed. The data for worst case post-baseline has been reported. Data values for the participants with abnormal clinically significant values are reported. Safety population was used for analysis.
Time Frame	Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, , the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Number [Participants]	0 0%	0 0%	0 0%	0 0%

43. Secondary Outcome

Title	Number of Participants With Abnormal ECG Findings, -Part 3B
Description	12-lead ECG, were measured in semi-supine position after 5 minutes rest. It was conducted as triplicate at screen and baseline, whereas single measure at other times, unless out of range then triplicates were performed. The data for worst case post-baseline has been reported. Data values for the participants with abnormal clinically significant values are reported. Safety population was used for analysis.
Time Frame	Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	32	30
Number [Participants]	0 0%	0 0%	0 0%	0 0%

44. Secondary Outcome

Title	Number of Participants With Hematology Values of Potential Clinical Importance (PCI)- Part1
Description	Blood samples were collected from the participants for analysis of hematology parameters like hematocrit, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.
Time Frame	Up to Day 3

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg Sodium laurilsulfate (SLS), with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Hematocrit, low	0 0%	0 0%	0 0%	0 0%	0 0%
Hematocrit, high	0 0%	0 0%	0 0%	0 0%	0 0%
Hemoglobin, low	0 0%	0 0%	0 0%	0 0%	0 0%
Hemoglobin, high	0 0%	0 0%	0 0%	0 0%	1 0.9%
Lymphocytes, low	0 0%	1 4.8%	0 0%	0 0%	0 0%
Lymphocyte, high	0 0%	0 0%	0 0%	0 0%	0 0%
Neutrophils, low	0 0%	0 0%	1 3%	1 3.1%	1 0.9%
Neutrophils, high	0 0%	0 0%	0 0%	0 0%	0 0%
Platelets, low	0 0%	0 0%	0 0%	0 0%	0 0%
Platelets, high	0 0%	0 0%	0 0%	0 0%	0 0%
Leukocytes, low	0 0%	2 9.5%	1 3%	1 3.1%	1 0.9%
Leukocytes, high	0 0%	0 0%	0 0%	0 0%	0 0%

45. Secondary Outcome

Title	Number of Participants With Hematology Values of PCI - Part 2
Description	Blood samples were collected from the participants for analysis of hematology parameters like hematocrit, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.
Time Frame	Day 2

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Hematocrit, low	0 0%	0 0%	0 0%	0 0%
Hematocrit, high	0 0%	0 0%	0 0%	0 0%
Hemoglobin, low	0 0%	0 0%	0 0%	0 0%
Hemoglobin, high	0 0%	0 0%	0 0%	0 0%
Lymphocytes, low	0 0%	0 0%	0 0%	0 0%
Lymphocytes, high	0 0%	0 0%	0 0%	0 0%
Neutrophils, low	1 3.8%	1 4.8%	0 0%	1 3.1%
Neutrophils, high	0 0%	0 0%	0 0%	0 0%
Platelets, low	1 3.8%	0 0%	0 0%	0 0%
Platelets, high	0 0%	0 0%	0 0%	00 0%
Leukocytes, low	0 0%	0 0%	0 0%	0 0%
Leukocytes, high	0 0%	0 0%	0 0%	0 0%

46. Secondary Outcome

Title	Number of Participants With Hematology Values of PCI - Part 3A
Description	Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of hematology parameters like hematocrit, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. It was conducted at Day 2 (48 hours). The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.
Time Frame	Day 2

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, , the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Hematocrit, low	0 0%	0 0%	0 0%	0 0%
Hematocrit, high	0 0%	0 0%	0 0%	0 0%
Hemoglobin, low	0 0%	0 0%	0 0%	0 0%
Hemoglobin, high	0 0%	0 0%	0 0%	0 0%
Lymphocytes, low	1 3.8%	1 4.8%	0 0%	0 0%
Lymphocytes, high	0 0%	0 0%	0 0%	0 0%
Neutrophils, low	0 0%	2 9.5%	0 0%	1 3.1%
Neutrophils, high	0 0%	0 0%	0 0%	0 0%
Platelets, low	0 0%	0 0%	0 0%	0 0%
Platelets, high	0 0%	0 0%	0 0%	0 0%
Leukocytes, low	0 0%	1 4.8%	0 0%	1 3.1%
Leukocytes, high	0 0%	0 0%	0 0%	0 0%

47. Secondary Outcome

Title	Number of Participants With Hematology Values of PCI - Part 3B
Description	Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of hematology parameters like hematocrit, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. It was conducted at Day 2 (48 hour). The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.
Time Frame	Day 2

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	32	30
Hematocrit, low	0 0%	0 0%	0 0%	0 0%
Hematocrit, high	0 0%	0 0%	0 0%	0 0%
Hemoglobin, low	0 0%	0 0%	0 0%	0 0%
Hemoglobin, high	0 0%	0 0%	0 0%	0 0%
Lymphocytes, low	0 0%	0 0%	0 0%	0 0%
Lymphocytes, high	0 0%	0 0%	0 0%	0 0%
Neutrophils, low	0 0%	2 9.5%	1 3%	2 6.3%
Neutrophils, high	0 0%	0 0%	0 0%	0 0%
Platelets, low	0 0%	0 0%	0 0%	0 0%
Platelets, high	0 0%	0 0%	0 0%	0 0%
Leukocytes, low	1 3.8%	1 4.8%	0 0%	1 3.1%
Leukocytes, high	0 0%	0 0%	0 0%	0 0%

48. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Values of PCI- Part1
Description	Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of clinical chemistry parameters like glucose, calcium, albumin, sodium and potassium. The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.
Time Frame	Day 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg Sodium laurilsulfate (SLS), with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 milligram (mg) + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Glucose, low	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, high	0 0%	0 0%	0 0%	0 0%	0 0%
Albumin, low	0 0%	0 0%	0 0%	0 0%	0 0%
Albumin, high	0 0%	0 0%	0 0%	0 0%	0 0%
Calcium, low	0 0%	0 0%	0 0%	0 0%	0 0%
Calcium, high	0 0%	0 0%	0 0%	0 0%	0 0%
Potassium, low	0 0%	0 0%	0 0%	0 0%	0 0%
Potassium, high	0 0%	0 0%	0 0%	0 0%	0 0%
Sodium, low	0 0%	0 0%	0 0%	0 0%	0 0%
Sodium, high	0 0%	0 0%	0 0%	0 0%	0 0%

49. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Values of PCI- Part 2
Description	Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of clinical chemistry parameters like glucose, calcium, albumin, sodium and potassium. It was collected at Day 2 (48 hour). The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.
Time Frame	Day 2

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies, ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Glucose, low	0 0%	0 0%	0 0%	0 0%
Glucose, high	0 0%	0 0%	0 0%	0 0%
Albumin, low	0 0%	0 0%	0 0%	0 0%
Albumin, high	0 0%	0 0%	0 0%	0 0%
Calcium, low	0 0%	0 0%	0 0%	0 0%
Calcium, high	0 0%	0 0%	0 0%	0 0%
Potassium, low	0 0%	0 0%	0 0%	0 0%
Potassium, high	0 0%	0 0%	0 0%	0 0%
Sodium, low	0 0%	0 0%	0 0%	0 0%
Sodium, high	0 0%	0 0%	0 0%	0 0%

50. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Values of PCI- Part 3A
Description	Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of clinical chemistry parameters like glucose, calcium, albumin, sodium and potassium. It was collected at (48 hour). The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.
Time Frame	Day 2

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, , the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Glucose, low	0 0%	0 0%	0 0%	0 0%
Glucose, high	0 0%	0 0%	0 0%	0 0%
Albumin, low	0 0%	0 0%	0 0%	0 0%
Albumin, high	0 0%	0 0%	0 0%	0 0%
Calcium, low	0 0%	0 0%	0 0%	0 0%
Calcium, high	0 0%	0 0%	0 0%	0 0%
Potassium, low	0 0%	0 0%	0 0%	0 0%
Potassium, high	0 0%	0 0%	0 0%	0 0%
Sodium, low	0 0%	0 0%	0 0%	0 0%
Sodium, high	0 0%	0 0%	0 0%	0 0%

51. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Values of PCI- Part 3B
Description	Blood samples of 2 mL, via a cannula for were collected from the participants for analysis of clinical chemistry parameters like glucose, calcium, albumin, sodium and potassium. It was collected at Day 2 (48 hour). The data for number of participants, with low and high values of PCI have been reported. Safety population was used for analysis.
Time Frame	Day 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	32	30
Glucose, low	0 0%	0 0%	0 0%	0 0%
Glucose, high	0 0%	0 0%	0 0%	0 0%
Albumin, low	0 0%	0 0%	0 0%	0 0%
Albumin, high	0 0%	0 0%	0 0%	0 0%
Calcium, low	0 0%	0 0%	0 0%	0 0%
Calcium, high	0 0%	0 0%	0 0%	0 0%
Potassium, low	0 0%	0 0%	0 0%	0 0%
Potassium, high	1 3.8%	0 0%	0 0%	0 0%
Sodium, low	0 0%	0 0%	0 0%	0 0%
Sodium, high	0 0%	0 0%	0 0%	0 0%

52. Secondary Outcome

Title	Number of Participants With Abnormal Urinalysis Results by Dipstick Method-Part 1
Description	Urine samples were collected at Day -1 (Baseline) and 48 hour, from the participants for urinalysis, by standard dipstick method. The parameters analyzed were ketones, glucose, occult blood, and protein. The number of participants with parameters detected as trace-lysed, trace-intact, trace, 2+ and 1+ was reported. Safety Population was used for analysis.
Time Frame	Up to Day 2

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Ketone, trace-lysed, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Ketone, trace-intact, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Ketone, trace, Day -1	2 7.7%	0 0%	0 0%	0 0%	1 0.9%
Ketone, 2+, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Ketone 1+, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Ketone, trace-lysed, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Ketone, trace-intact, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Ketone, trace, 48 hour	0 0%	1 4.8%	0 0%	0 0%	0 0%
Ketone, 2+, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Ketone 1+, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, trace-lysed, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, trace-Intact, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, trace, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, 2+, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, 1+, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, trace-lysed, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, trace-Intact, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, trace, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, 2+, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, 1+, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Occult blood, trace-lysed, Day -1	0 0%	1 4.8%	0 0%	1 3.1%	0 0%
Occult blood, trace-Intact, Day -1	0 0%	1 4.8%	0 0%	1 3.1%	1 0.9%
Occult blood, trace, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Occult blood, 2+, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Occult blood, 1+, Day -1	0 0%	1 4.8%	1 3%	0 0%	1 0.9%
Occult blood, trace-lysed, 48 hour	1 3.8%	1 4.8%	0 0%	1 3.1%	0 0%
Occult blood, trace-Intact, 48 hour	0 0%	0 0%	2 6.1%	1 3.1%	3 2.7%
Occult blood, trace, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Occult blood, 2+, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Occult blood, 1+, 48 hour	2 7.7%	1 4.8%	0 0%	0 0%	0 0%
Protein, trace-lysed, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Protein, trace-Intact, Day -1	0 0%	0 0%	0 0%	0 0%	0 0%
Protein, trace, Day -1	1 3.8%	0 0%	0 0%	0 0%	0 0%
Protein, 2+, Day -1	0 0%	0 0%	0 0%	0 0%	1 0.9%
Protein, 1+, Day -1	1 3.8%	0 0%	1 3%	1 3.1%	0 0%
Protein, trace-lysed, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Protein, trace-Intact, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Protein, trace, 48 hour	0 0%	0 0%	0 0%	0 0%	1 0.9%
Protein, 2+, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%
Protein, 1+, 48 hour	0 0%	0 0%	0 0%	0 0%	0 0%

53. Secondary Outcome

Title	Number of Participants With Urinalysis Results by Dipstick Analysis-Part 2
Description	Urine samples were collected at Day -1 (Baseline) and 48 hour, from the participants for urinalysis, by standard dipstick method. The parameters analyzed were ketones, glucose, occult blood, and protein. The number of participants with parameters detected as trace-lysed, trace-intact, trace, 2+ and 1+ was reported. Safety Population was used for analysis
Time Frame	Up to Day 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 milligram (mg) + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Ketone, trace-intact, Day -1	0 0%	0 0%	0 0%	0 0%
Ketone, trace, Day -1	1 3.8%	2 9.5%	2 6.1%	1 3.1%
Ketone, 2+, Day -1	0 0%	0 0%	0 0%	0 0%
Ketone, trace-intact, 48 hour	0 0%	0 0%	0 0%	0 0%
Ketone, trace, 48 hour	1 3.8%	0 0%	1 3%	0 0%
Ketone, 2+, 48 hour	0 0%	0 0%	0 0%	1 3.1%
Glucose, trace-Intact, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, trace, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, 2+, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, trace-Intact, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, trace, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, 2+, 48 hour	0 0%	0 0%	0 0%	0 0%
Occult blood, trace-Intact, Day -1	0 0%	1 4.8%	0 0%	1 3.1%
Occult blood, trace, Day -1	0 0%	0 0%	0 0%	0 0%
Occult blood, 2+, Day -1	0 0%	0 0%	0 0%	0 0%
Occult blood, trace-Intact, 48 hour	0 0%	0 0%	0 0%	1 3.1%
Occult blood, trace, 48 hour	0 0%	0 0%	0 0%	0 0%
Occult blood, 2+, 48 hour	0 0%	0 0%	0 0%	0 0%
Protein, trace-Intact, Day -1	0 0%	0 0%	0 0%	0 0%
Protein, trace, Day -1	1 3.8%	2 9.5%	2 6.1%	0 0%
Protein, 2+, Day -1	0 0%	0 0%	0 0%	0 0%
Protein, trace-Intact, 48 hour	0 0%	0 0%	0 0%	0 0%
Protein, trace, 48 hour	3 11.5%	1 4.8%	3 9.1%	3 9.4%
Protein, 2+, 48 hour	1 3.8%	0 0%	0 0%	0 0%

54. Secondary Outcome

Title	Number of Participants With Urinalysis Results by Dipstick Analysis-Part 3A
Description	Urine samples were collected at Day -1 (Baseline) and 48 hour, from the participants for urinalysis, by standard dipstick method. The parameters analyzed were ketones, glucose, occult blood, and protein. The number of participants with parameters detected as trace-lysed, trace-intact, trace, 2+ and 1+ was reported. Safety Population was used for analysis.
Time Frame	Up to Day 2

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, , the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Ketone, trace-lysed, Day -1	0 0%	0 0%	0 0%	0 0%
Ketone, trace-intact, Day -1	0 0%	0 0%	0 0%	0 0%
Ketone, trace, Day -1	4 15.4%	3 14.3%	4 12.1%	4 12.5%
Ketone, 2+, Day -1	0 0%	0 0%	0 0%	0 0%
Ketone 1+, Day -1	0 0%	0 0%	1 3%	0 0%
Ketone, trace-lysed, 48 hour	0 0%	0 0%	0 0%	0 0%
Ketone, trace-intact, 48 hour	0 0%	0 0%	0 0%	0 0%
Ketone, trace, 48 hour	2 7.7%	1 4.8%	1 3%	3 9.4%
Ketone, 2+, 48 hour	0 0%	0 0%	0 0%	0 0%
Ketone 1+, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, trace-lysed, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, trace-Intact, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, trace, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, 2+, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, 1+, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, trace-lysed, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, trace-Intact, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, trace, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, 2+, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, 1+, 48 hour	0 0%	0 0%	0 0%	0 0%
Occult blood, trace-lysed, Day -1	3 11.5%	6 28.6%	4 12.1%	3 9.4%
Occult blood, trace-Intact, Day -1	4 15.4%	2 9.5%	1 3%	1 3.1%
Occult blood, trace, Day -1	0 0%	0 0%	0 0%	0 0%
Occult blood, 2+, Day -1	0 0%	1 4.8%	2 6.1%	0 0%
Occult blood, 1+, Day -1	0 0%	0 0%	0 0%	0 0%
Occult blood, trace-lysed, 48 hour	1 3.8%	5 23.8%	2 6.1%	2 6.3%
Occult blood, trace-Intact, 48 hour	3 11.5%	0 0%	1 3%	0 0%
Occult blood, trace, 48 hour	0 0%	0 0%	0 0%	0 0%
Occult blood, 2+, 48 hour	0 0%	0 0%	0 0%	0 0%
Occult blood, 1+, 48 hour	0 0%	0 0%	1 3%	1 3.1%
Protein, trace-lysed, Day -1	0 0%	0 0%	0 0%	0 0%
Protein, trace-Intact, Day -1	0 0%	0 0%	0 0%	0 0%
Protein, trace, Day -1	1 3.8%	0 0%	0 0%	2 6.3%
Protein, 2+, Day -1	0 0%	0 0%	0 0%	0 0%
Protein, 1+, Day -1	0 0%	0 0%	0 0%	0 0%
Protein, trace-lysed, 48 hour	0 0%	0 0%	0 0%	0 0%
Protein, trace-Intact, 48 hour	0 0%	0 0%	0 0%	0 0%
Protein, trace, 48 hour	2 7.7%	0 0%	0 0%	2 6.3%
Protein, 2+, 48 hour	0 0%	0 0%	0 0%	0 0%
Protein, 1+, 48 hour	0 0%	0 0%	0 0%	0 0%

55. Secondary Outcome

Title	Number of Participants With Urinalysis Results by Dipstick Analysis-Part 3B
Description	Urine samples were collected at Day -1 (Baseline) and 48 hour, from the participants for urinalysis, by standard dipstick method. The parameters analyzed were ketones, glucose, occult blood, and protein. The number of participants with parameters detected as trace-lysed, trace-intact, trace, 2+ and 1+ was reported. Safety Population was used for analysis.
Time Frame	Up to Day 2

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	32	30
Ketone, trace-lysed, Day -1	0 0%	0 0%	0 0%	0 0%
Ketone, trace-intact, Day -1	0 0%	0 0%	0 0%	0 0%
Ketone, trace, Day -1	1 3.8%	4 19%	4 12.1%	1 3.1%
Ketone, 3+, Day -1	0 0%	1 4.8%	0 0%	0 0%
Ketone, trace-lysed, 48 hour	0 0%	0 0%	0 0%	0 0%
Ketone, trace-intact, 48 hour	0 0%	0 0%	0 0%	0 0%
Ketone, trace, 48 hour	1 3.8%	0 0%	1 3%	2 6.3%
Ketone, 3+, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, trace-lysed, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, trace-Intact, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, trace, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, 3+, Day -1	0 0%	0 0%	0 0%	0 0%
Glucose, trace-lysed, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, trace-Intact, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, trace, 48 hour	0 0%	0 0%	0 0%	0 0%
Glucose, 3+, 48 hour	0 0%	0 0%	0 0%	0 0%
Occult blood, trace-lysed, Day -1	2 7.7%	0 0%	0 0%	0 0%
Occult blood, trace-Intact, Day -1	0 0%	1 4.8%	3 9.1%	1 3.1%
Occult blood, trace, Day -1	0 0%	0 0%	0 0%	0 0%
Occult blood, 3+, Day -1	0 0%	0 0%	0 0%	0 0%
Occult blood, trace-lysed, 48 hour	0 0%	0 0%	0 0%	0 0%
Occult blood, trace-Intact, 48 hour	0 0%	0 0%	0 0%	1 3.1%
Occult blood, trace, 48 hour	0 0%	0 0%	0 0%	0 0%
Occult blood, 3+, 48 hour	1 3.8%	0 0%	0 0%	0 0%
Protein, trace-lysed, Day -1	0 0%	0 0%	0 0%	0 0%
Protein, trace-Intact, Day -1	0 0%	0 0%	0 0%	0 0%
Protein, trace, Day -1	0 0%	1 4.8%	1 3%	2 6.3%
Protein, 3+, Day -1	0 0%	0 0%	0 0%	0 0%
Protein, trace-lysed, 48 hour	0 0%	0 0%	0 0%	0 0%
Protein, trace-Intact, 48 hour	0 0%	0 0%	0 0%	0 0%
Protein, trace, 48 hour	2 7.7%	1 4.8%	0 0%	1 3.1%
Protein, 3+, 48 hour	0 0%	0 0%	0 0%	0 0%

56. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)-Part 1
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Safety population was used for analysis.
Time Frame	Up to 42 days

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Part 1,Treatment F1	Part 1,Treatment F2	Part 1,Treatment F3	Part 1,Treatment F4	Part 1, Treatment R
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.	In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.	In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.	In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.	In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.
Measure Participants	21	23	23	22	21
Any SAE	0 0%	0 0%	0 0%	0 0%	0 0%
Any AE	12 46.2%	13 61.9%	13 39.4%	15 46.9%	12 10.7%

57. Secondary Outcome

Title	Number of Participants With SAEs and AEs-Part 2
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Safety population was used for analysis.
Time Frame	Up to 35 days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 2, Treatment R	Part 2, Treatment FG1	Part 2, Treatment FG2	Part 2, Treatment FG3
Arm/Group Description	Participants were administered 2 monotherapies ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.	Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.	Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.	Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.
Measure Participants	21	20	20	20
Any SAE	0 0%	0 0%	0 0%	0 0%
Any AE	13 50%	12 57.1%	14 42.4%	12 37.5%

58. Secondary Outcome

Title	Number of Participants With SAEs and AEs-Part 3A
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Safety population was used for analysis.
Time Frame	Up to 44 days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 3A,Treatment X1	Part 3A,Treatment X2	Part 3A,Treatment R1	Part 3A,Treatment R2
Arm/Group Description	In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, participants received a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.	In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.	In the R1 arm, of Part 3A, , the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.	In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.
Measure Participants	32	33	32	32
Any SAE	0 0%	0 0%	0 0%	0 0%
Any AE	24 92.3%	21 100%	25 75.8%	23 71.9%

59. Secondary Outcome

Title	Number of Participants With SAEs and AEs-Part 3B
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Safety population was used for analysis.
Time Frame	Up to 44 days

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part 3B,Treatment Y1	Part 3B,Treatment Y2	Part 3B,Treatment R3	Part 3B,Treatment R4
Arm/Group Description	In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2	In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.	In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.	In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
Measure Participants	30	31	32	30
Any SAE	0 0%	0 0%	0 0%	0 0%
Any AE	20 76.9%	18 85.7%	24 72.7%	15 46.9%

Adverse Events

Time Frame	All SAEs and AEs were collected from Day 1 to up to follow-up ( up to 165 days)
Adverse Event Reporting Description	Safety population included all the participants enrolled into the study who received atleast one dose of investigational product, was used to assess AE's and SAE's
Arm/Group Title	Part 1,Treatment F1		Part 1,Treatment F2		Part 1,Treatment F3		Part 1,Treatment F4		Part 1, Treatment R		Part 2, Treatment R		Part 2, Treatment FG1		Part 2, Treatment FG2		Part 2, Treatment FG3		Part 3A,Treatment X1		Part 3A,Treatment X2		Part 3A,Treatment R1		Part 3A,Treatment R2		Part 3B,Treatment Y1		Part 3B,Treatment Y2		Part 3B,Treatment R3		Part 3B,Treatment R4
Arm/Group Description	In the F1 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC1- GSK3380154, TAB-A, Tablet Weight 840mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F2.		In the F2 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): FDC2- GSK3380154, TAB-A, Tablet Weight 840mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F3.		In the F3 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TABA, Tablet Weight 560mg/2mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose F4.		In the F4 arm of Part 1, the participants had received the FDC with dose session as (ambrisentan 10 mg + tadalafil 40 mg): GSK3380154, TAB-A, Tablet Weight 560mg/4mg SLS, with reference to the 2 monotherapy components for ambrisentan 10 mg and tadalafil 40 mg, which were taken concurrently, which evaluated bioavailability. This was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.		In the R arm of Part 1, the participants had received the 2 monotherapies ambrisentan 10 mg and tadalafil 40 mg concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.		Participants were administered 2 monotherapies ambrisentan and tadalafil concurrently. The tablets were taken as single oral dose, under fasting condition and was followed by a wash-out period of 7-days.		Participants were administered the FDC-G1 granulation size 1 (ambrisentan 10 mg + tadalafil 40 mg) , from the formulation selected from Part 1. FG1 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG2.		Participants were administered the FDC-G2 granulation size 2 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG2 was administered as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose FG3.		Participants were administered the FDC-G3 granulation size 3 (ambrisentan 10 mg + tadalafil 40 mg) from the formulation selected from Part 1. FG3 was received as a single oral dose, under fasting condition and was followed by a wash-out period of 7-days, before the start of next dose R.		In the X1 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg) either FG1, FG2 or FG3 (from granular formulation selected from Part 2), under fed state as a single oral dose. The fed state, particpants recived a high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose X2.		In the X2 arm of Part 3A, which evaluated the bioequivalence, the participants had received FDC (ambrisentan 10 mg + tadalafil 40 mg), either FG1, FG2 or FG3 (the granular formulation selected from Part 2), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R1.		In the R1 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fed state. Fed state comprised of high fat diet. This was followed by a wash-out period of 10-days, before the start of next dose R2.		In the R2 arm, of Part 3A, the participants had received the 2 monotherapies, for ambrisentan 10 mg and tadalafil 40 mg, as single oral dose, under fasted state. This was followed by a wash-out period of 10-days.		In the Y1 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 40 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose Y2		In the Y2 arm of Part 3B, which evaluated bioequivalence, the participants had received FDC (ambrisentan 5 mg + tadalafil 20 mg), under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose R3.		In the R3 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 40 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days, before the start of next dose of R4.		In the R4 arm of Part 3B, which evaluated bioequivalence, the participants had received the 2 monotherapies, for ambrisentan 5 mg and tadalafil 20 mg, under fasted state as a single oral dose. This was followed by a wash-out period of 10-days.
All Cause Mortality
	Part 1,Treatment F1		Part 1,Treatment F2		Part 1,Treatment F3		Part 1,Treatment F4		Part 1, Treatment R		Part 2, Treatment R		Part 2, Treatment FG1		Part 2, Treatment FG2		Part 2, Treatment FG3		Part 3A,Treatment X1		Part 3A,Treatment X2		Part 3A,Treatment R1		Part 3A,Treatment R2		Part 3B,Treatment Y1		Part 3B,Treatment Y2		Part 3B,Treatment R3		Part 3B,Treatment R4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/23 (0%)		0/23 (0%)		0/22 (0%)		0/21 (0%)		0/21 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)		0/32 (0%)		0/33 (0%)		0/32 (0%)		0/32 (0%)		0/30 (0%)		0/31 (0%)		0/32 (0%)		0/30 (0%)
Serious Adverse Events
	Part 1,Treatment F1		Part 1,Treatment F2		Part 1,Treatment F3		Part 1,Treatment F4		Part 1, Treatment R		Part 2, Treatment R		Part 2, Treatment FG1		Part 2, Treatment FG2		Part 2, Treatment FG3		Part 3A,Treatment X1		Part 3A,Treatment X2		Part 3A,Treatment R1		Part 3A,Treatment R2		Part 3B,Treatment Y1		Part 3B,Treatment Y2		Part 3B,Treatment R3		Part 3B,Treatment R4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/23 (0%)		0/23 (0%)		0/22 (0%)		0/21 (0%)		0/21 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)		0/32 (0%)		0/33 (0%)		0/32 (0%)		0/32 (0%)		0/30 (0%)		0/31 (0%)		0/32 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Part 1,Treatment F1		Part 1,Treatment F2		Part 1,Treatment F3		Part 1,Treatment F4		Part 1, Treatment R		Part 2, Treatment R		Part 2, Treatment FG1		Part 2, Treatment FG2		Part 2, Treatment FG3		Part 3A,Treatment X1		Part 3A,Treatment X2		Part 3A,Treatment R1		Part 3A,Treatment R2		Part 3B,Treatment Y1		Part 3B,Treatment Y2		Part 3B,Treatment R3		Part 3B,Treatment R4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/21 (47.6%)		12/23 (52.2%)		13/23 (56.5%)		14/22 (63.6%)		12/21 (57.1%)		13/21 (61.9%)		12/20 (60%)		14/20 (70%)		12/20 (60%)		22/32 (68.8%)		21/33 (63.6%)		24/32 (75%)		22/32 (68.8%)		19/30 (63.3%)		17/31 (54.8%)		22/32 (68.8%)		13/30 (43.3%)
Cardiac disorders
Palpitations	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	2/32 (6.3%)	2	0/33 (0%)	0	1/32 (3.1%)	1	1/32 (3.1%)	1	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Eye disorders
Eye swelling	1/21 (4.8%)	1	2/23 (8.7%)	2	0/23 (0%)	0	1/22 (4.5%)	1	0/21 (0%)	0	0/21 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Photophobia	0/21 (0%)	0	1/23 (4.3%)	1	3/23 (13%)	3	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Eye pain	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	3/32 (9.4%)	3	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Gastrointestinal disorders
Nausea	0/21 (0%)	0	2/23 (8.7%)	2	1/23 (4.3%)	1	0/22 (0%)	0	0/21 (0%)	0	1/21 (4.8%)	1	1/20 (5%)	1	1/20 (5%)	1	3/20 (15%)	3	3/32 (9.4%)	3	3/33 (9.1%)	3	2/32 (6.3%)	2	5/32 (15.6%)	5	3/30 (10%)	3	2/31 (6.5%)	2	3/32 (9.4%)	3	0/30 (0%)	0
Vomiting	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	1/32 (3.1%)	1	2/33 (6.1%)	2	1/32 (3.1%)	1	2/32 (6.3%)	2	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Gastrooesophageal reflux disease	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	2/32 (6.3%)	2	0/33 (0%)	0	1/32 (3.1%)	1	2/32 (6.3%)	2	0/30 (0%)	0	0/31 (0%)	0	2/32 (6.3%)	2	0/30 (0%)	0
General disorders
Fatigue	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	1/21 (4.8%)	1	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Gait disturbance	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Immune system disorders
Seasonal allergy	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Infections and infestations
Viral upper respiratory tract infection	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Metabolism and nutrition disorders
Polydipsia	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/21 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1	2/22 (9.1%)	2	1/21 (4.8%)	1	0/21 (0%)	0	1/20 (5%)	1	2/20 (10%)	2	1/20 (5%)	1	1/32 (3.1%)	1	5/33 (15.2%)	5	3/32 (9.4%)	3	1/32 (3.1%)	1	4/30 (13.3%)	4	1/31 (3.2%)	1	4/32 (12.5%)	4	1/30 (3.3%)	1
Musculoskeletal pain	2/21 (9.5%)	2	0/23 (0%)	0	0/23 (0%)	0	1/22 (4.5%)	1	1/21 (4.8%)	1	3/21 (14.3%)	3	0/20 (0%)	0	0/20 (0%)	0	3/20 (15%)	3	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/31 (3.2%)	1	2/32 (6.3%)	2	0/30 (0%)	0
Limb discomfort	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Pain in extremity	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	3/32 (9.4%)	4	2/33 (6.1%)	2	5/32 (15.6%)	5	1/32 (3.1%)	1	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Nervous system disorders
Headache	6/21 (28.6%)	6	11/23 (47.8%)	11	10/23 (43.5%)	10	13/22 (59.1%)	15	10/21 (47.6%)	12	13/21 (61.9%)	14	9/20 (45%)	10	13/20 (65%)	15	11/20 (55%)	11	17/32 (53.1%)	18	20/33 (60.6%)	21	22/32 (68.8%)	24	22/32 (68.8%)	23	18/30 (60%)	18	13/31 (41.9%)	13	16/32 (50%)	16	10/30 (33.3%)	10
Dizziness	1/21 (4.8%)	1	2/23 (8.7%)	2	1/23 (4.3%)	1	1/22 (4.5%)	1	1/21 (4.8%)	1	0/21 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Psychiatric disorders
Euphoric mood	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Insomnia	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Reproductive system and breast disorders
Erection increased	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	1/21 (4.8%)	1	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Priapism	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/31 (0%)	0	1/32 (3.1%)	1	2/30 (6.7%)	2
Respiratory, thoracic and mediastinal disorders
Nasal congestion	4/21 (19%)	4	3/23 (13%)	3	2/23 (8.7%)	2	2/22 (9.1%)	2	1/21 (4.8%)	1	3/21 (14.3%)	3	3/20 (15%)	3	3/20 (15%)	3	2/20 (10%)	2	2/32 (6.3%)	2	3/33 (9.1%)	3	3/32 (9.4%)	3	1/32 (3.1%)	1	1/30 (3.3%)	1	1/31 (3.2%)	1	2/32 (6.3%)	2	2/30 (6.7%)	2
Epistaxis	0/21 (0%)	0	1/23 (4.3%)	1	1/23 (4.3%)	1	1/22 (4.5%)	1	2/21 (9.5%)	2	0/21 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	1/20 (5%)	1	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0
Vascular disorders
Flushing	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	1/20 (5%)	1	1/32 (3.1%)	1	0/33 (0%)	0	1/32 (3.1%)	1	2/32 (6.3%)	2	0/30 (0%)	0	2/31 (6.5%)	2	0/32 (0%)	0	2/30 (6.7%)	2
Hot flush	0/21 (0%)	0	0/23 (0%)	0	0/23 (0%)	0	0/22 (0%)	0	0/21 (0%)	0	0/21 (0%)	0	1/20 (5%)	1	1/20 (5%)	1	0/20 (0%)	0	0/32 (0%)	0	0/33 (0%)	0	0/32 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	0/31 (0%)	0	0/32 (0%)	0	0/30 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.