Relative bioavailability study of marketed and lower dose ambrisentan in healthy adult participants
- Conditions
- Pulmonary arterial hypertensionMedDRA version: 21.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2019-001699-12-GB
- Lead Sponsor
- GlaxoSmithKline Research and Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 24
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 <1% per year as described in Appendix 4 of the study protocol.
b. Female participants
A female participant is eligible to participate if she is not a woman of childbearing potential (WOCBP), as defined in Appendix 4 of the study protocol
6. Capable of giving signed informed consent as described in Appendix 1 of the study protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
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 <133 g/L for male participants; and Hb <114 g/L for female participants)
4. Alanine transaminase (ALT) >1.5x upper limit of normal (ULN)
5. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
6. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
7. QTc >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method