Pulmonary arterial hypertension MedDRA version: 21.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Ambrisentan Tablet
Product Code: GSK1325760
Pharmaceutical Form: Tablet
INN or Proposed INN: AMBRISENTAN
CAS Number: 177036-94-1
Other descriptive name: (S)-2-(4,6-dimethylpyrimidin-2-yl
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent 2. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring (refer to Section 5.4 for information about rescreening). 3. Average systolic blood pressure between 100-160 mmHg and diastolic between 55-90 mmHg (inclusive) over 3 readings at screening 4. Body weight >50 kg for men and = 45kg for women, and body mass index (BMI) within the range 18-30 kg/m2 (inclusive). 5. Male or Female a. Male Participants Male participants are eligible to participate if they agree to the following during the study and for at least 13 weeks afterwards corresponding to time needed to eliminate study intervention (5 terminal half-lives) plus an additional 90 days (a spermatogenesis cycle): ?Refrain from donating sperm PLUS either: ?Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR ?Must agree to use contraception/barrier, as follows: ?Agree to use a male condom; and ?Female partner to use an additional highly effective contraceptive method with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data 2. History or presence of palpitations or tachyarrhythmias 3. Haemoglobin (Hb) below the normal range (Hb 1.5x upper limit of normal (ULN) 5. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 450 msec NOTES: ?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. ?The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial. 8. Past or intended use of over-the-counter or prescription medication (including vitamins and dietary or herbal supplements but excluding paracetamol =2 g/day) within 7 days (or 14 days if the drug is a potential enzyme inhibitor) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless approved by the Investigator in conjunction with GSK Medical Monitor. 9. Participation in the study would result in loss of blood or blood products in excess of 500 mL within a 56-day period 10. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day 11. Current enrolment or past participation within 30 days before screening in any other clinical study involving an investigational study intervention or any other type of medical research 12. Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention 13. Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention. NOTE: Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained 14. Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention. NOTE: Test is optional and subjects with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing 15. Positive human immunodeficiency virus (HIV) antibody test 16. Positive pre-study drug/alcohol screen 17. Regular use of known drugs of abuse 18. Regular alcohol consumption within 6 months prior to the study defined as: ?An average weekly intake of >14 units. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. 19. Smoking > 5 cigarettes per week (or equivalent) and participants must be able to abstain from smoking for a 24-hour
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Plasma pharmacokinetic parameters of AMB, as data permit: Cmax, tmax, AUC (0-8), AUC(0-t) and t½.;Timepoint(s) of evaluation of this end point: PK samples collected at the following timepoints in each treatment period: Pre-dose, Post dose (hrs); 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48, 72.;Main Objective: To compare the relative bioavailability of AMB (1 mg x 5 tablets) administered as tablets dispersed in water or administered orally, with marketed AMB (5 mg x 1 tablet) administered orally, in healthy adult participants under fasted conditions.;Secondary Objective: To monitor the safety and tolerability of AMB (1 mg x 5 tablets) administered as tablets dispersed in water or administered orally, compared with marketed AMB (5 mg x 1 tablet) administered orally, in healthy adult participants. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Adverse events (AE), vital signs, electrocardiogram (ECG), and clinical laboratory values.;Timepoint(s) of evaluation of this end point: Adverse Events will be continually assessed throughout the study and at follow up. Vital signs will be assessed at the following timepoints: Pre-dose, Post-dose (hrs); 0.5, 1, 2, 4, 8, 12, 24, 48, 72. ECG’s will be conducted at the following timepoints: Pre-dose, Post-dose (hrs); 1, 2, 4, 12, 24, 72. Clinical chemistry, hematology and urinalysis values will be collected at the following timepoints: Day -1 (admission to unit) and 48 post dose. Additional tests may be performed at any time during the study as determined necessary by the investigator. | — |
Countries
United Kingdom
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed