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NCT Number: NCT02688387

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

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.

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Key information

Conditions

Hypertension, Pulmonary Cardiovascular Diseases Hypertension Lung Diseases Respiratory Tract Diseases Vascular Diseases

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site

London, NW10 7EW, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

Drug

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

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

Drug

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.

Primary outcomes

  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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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 outcomes

  1. Time Taken to Reach Maximum Concentration (Tmax) for Ambrisentan and Tadalafil in FDC and Reference Treatment - Part 1

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Collaborators

  • Covance Harrogate
  • Hammersmith Medicines Research

Registry information

Official study title

A Phase 1 Study to Demonstrate the Relative Bioavailability of Fixed Dose Combinations of Ambrisentan and Tadalafil in Healthy Subjects

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Feb 23, 2016
Registry last updated
Jan 22, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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