Hypertension, PulmonaryPhase 1NCT04095286

Relative Bioavailability Study of Marketed and Lower Dose Ambrisentan in Healthy Adult Participants

A Phase 1 study testing AMB new formulation (1 mg) and Reference AMB (5 mg) in people with Hypertension, Pulmonary, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Hypertension, Pulmonary
What is being tested?: AMB new formulation (1 mg) and Reference AMB (5 mg)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 29 participants
Where: 1 siteUnited Kingdom
Study dates: 30 Sep 2019to 17 Dec 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring.
Average systolic blood pressure between 100-160 millimeter of mercury (mmHg) and diastolic between 55-90 mmHg (inclusive) over 3 readings at Screening.
Body weight >=50 kilogram (kg) for men and >= 45kg for women, and body mass index (BMI) within the range 18-30 kilogram per meter square (kg/m^2) (inclusive).
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): 1. Refrain from donating sperm plus either 2. 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.
A female participant is eligible to participate if she is not a woman of childbearing potential (WOCBP).
Capable of giving signed informed consent.

Who cannot join

History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,endocrine, hematological, 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.
History or presence of palpitations or tachyarrhythmia.
Hemoglobin (Hb) below the normal range (Hb <133 grams per liter [g/L] for male participants ; and Hb <114 g/L for female participants).
Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN)
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

Show all 20Show fewer

Corrected QT interval (QTc) >450 millisecond (msec).
Past or intended use of over-the-counter or prescription medication (including vitamins and dietary or herbal supplements but excluding paracetamol <=2 grams/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 GlaxoSmithKline Medical Monitor.
Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within a 56-day period.
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
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.
Presence of Hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to first dose of study intervention.
Positive Hepatitis C antibody test result at Screening or within 3 months prior to first dose of study intervention.
Positive Hepatitis C Ribonucleic acid (RNA) test result at Screening or within 3 months prior to first dose of study intervention.
Positive human immunodeficiency virus (HIV) antibody test.
Positive pre-study drug/alcohol screen.
Regular use of known drugs of abuse.
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 grams of alcohol: a half-pint (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Smoking > 5 cigarettes per week (or equivalent) and participants must be able to abstain from smoking for a 24-hour period prior to dose and any time whilst in the clinical unit.
Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Cambridge, Cambridgeshire, CB2 2GG

Other trials in United Kingdom

About this study

Official title: An Open-label, Randomized Three Period Cross-over Relative Bioavailability Study to Compare the Pharmacokinetic Parameters of a Lower Dose Formulation of Ambrisentan (GSK1325760) With Marketed Ambrisentan in Healthy Adult Participants

This is a single center, open-label, randomized, single-dose, three-period cross-over study in healthy participants. The aim of this study is to provide clinically relevant information on the pharmacokinetic (PK) and safety profile of a new lower dose formulation ambrisentan (AMB) tablet, which is intended for pediatric use. The study will compare the relative bioavailability of the lower dose tablet, dispersed in water and administered orally, with the reference marketed AMB tablet in healthy adults. The total study duration for each participant is expected to be approximately 9 weeks.

Conditions: Hypertension, Pulmonary
Being tested: AMB new formulation (1 mg), Reference AMB (5 mg)
Keywords: Ambrisentan, Oral dosage forms, Pulmonary arterial hypertension, Bioavailability
Medical subject headings: Hypertension, Pulmonary, Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AMB new formulation (1 mg)Drug
AMB tablets will be available at a unit dose strength of 1 mg. Participants will orally administer 5 tablets of 1 mg unit dose.
Reference AMB (5 mg)Drug
AMB reference tablet will be available as film-coated tablet at unit dose strength of 5 mg. Participants will orally administer 1 tablet of 5 mg unit dose

Study groups in NCT04095286
Study group	Role	What they receive
AMB dispersed in water/AMB oral tablet/reference AMB	Experimental	Eligible participants will receive a single oral dose of 5 milligram (mg) AMB tablet dispersed in water during treatment period 1 followed by a single dose of 5 mg AMB oral tablet in treatment period 2. In treatment period 3, participants will receive a single oral dose of reference 5 mg AMB tablet. There will be a washout period of 7 days between doses in each treatment period. Receives: Drug: AMB new formulation (1 mg); Drug: Reference AMB (5 mg)
AMB oral tablet/reference AMB/AMB dispersed in water	Experimental	Eligible participants will receive single dose of 5 mg AMB oral tablet during treatment period 1 followed by single dose of reference 5 mg AMB oral tablet in treatment period 2. In treatment period 3, participants will receive single dose of 5 mg AMB tablet dispersed in water. There will be a washout period of 7 days between doses in each treatment period. Receives: Drug: AMB new formulation (1 mg); Drug: Reference AMB (5 mg)
Reference AMB/AMB dispersed in water/AMB oral tablet	Experimental	Eligible participants will receive single dose of reference 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB tablet dispersed in water in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period. Receives: Drug: AMB new formulation (1 mg); Drug: Reference AMB (5 mg)
AMB dispersed in water/reference AMB/AMB oral tablet	Experimental	Eligible participants will receive single dose of 5 mg AMB tablet dispersed in water during treatment period 1 followed by single dose of reference 5 mg AMB oral tablet in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period. Receives: Drug: AMB new formulation (1 mg); Drug: Reference AMB (5 mg)
AMB oral tablet/AMB dispersed in water/reference AMB	Experimental	Eligible participants will receive single dose of 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB tablet dispersed in water in treatment period 2. In treatment period 3 participants will receive single dose of reference 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period. Receives: Drug: AMB new formulation (1 mg); Drug: Reference AMB (5 mg)
Reference AMB/AMB oral/AMB dispersed in water	Experimental	Eligible participants in this arm will receive single dose of reference 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB oral tablet in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB tablet dispersed in water There will be a washout period of 7 days between doses in each treatment period. Receives: Drug: AMB new formulation (1 mg); Drug: Reference AMB (5 mg)

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Plasma Concentration (Cmax) After Administration of AMB Under Fasted Condition
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who provided PK parameter data.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Time to Cmax (Tmax) After Administration of AMB Under Fasted Condition
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Time of Last Quantifiable Concentration (Tlast) After Administration of AMB Under Fasted Condition
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [(AUC(0-inf)] After Administration of AMB Under Fasted Condition
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Area Under the Plasma Concentration-time Curve From Time Zero to Last Time of Quantifiable Concentration [AUC(0-t)] After Administration of AMB Under Fasted Condition
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Apparent Terminal Phase Half-life (t1/2) After Administration of AMB Under Fasted Condition
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose

Secondary outcomes (6)

Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=2%)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment were categorized as SAE.
Measured: Up to 40 days
Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Vital signs were measured in semi-supine position after 5 minutes rest and included Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Heart rate (HR). Data for number of participants with Post-Baseline worst case Vital Sign results relative to PCI Criteria relative to Baseline has been presented. Participants are counted in worst case category that their value changes to low, within range or high. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in "Within Range or No Change" category. Participants are counted twice if values changed 'To Low' and 'To High', so the percentages are not added to 100%. Participants with missing baseline value are assumed as within range value. PCI ranges were: SBP [lower: <85, upper: >160 millimeter of mercury (mmHg)]; DBP (lower: <40, upper: >110 mmHg); HR (lower: <45, upper: >100 beats per minute). The value at Day 1 was considered as Baseline.
Measured: Baseline (Day 1) and up to 40 days
Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
12-lead ECGs were recorded in semi-supine position after 5 minutes rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Data for number of participants with abnormal clinically significant ECG findings for worst case post-Baseline has been presented. Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. The value at Day 1 was considered as Baseline.
Measured: Baseline (Day 1) and up to 40 days
Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Blood samples were collected to analyze hemoglobin, hematocrit, lymphocytes, total neutrophils, platelet count, and white blood cell(WBC) counts. PCI ranges were hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from Baseline <0.075); hemoglobin(high: >180 grams per liter[g/L] and low: change from Baseline <25 g/L); lymphocytes (low: <0.8 Giga cells per liter[GI/L]); platelet count (low: <100 GI/L and high: >550 GI/L); neutrophil count (low: <1.5 GI/L); WBC count (low: <3 GI/L and high: >20 GI/L). Participants were counted in worst-case category that their value changed to low, within range or no change, or high unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in ''To within Range or No Change' category. Participants were counted twice if participant had both values that changed 'To Low' and 'To High'. Baseline is defined as Day -1.
Measured: Baseline (Day -1) and up to 40 days
Number of Participants With Worst Case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Blood samples were collected to analyze PCI ranges for aspartate amino transferase (AST), alanine amino transferase (ALT), \& alkaline phosphatase (ALP) (high: >=2 times (*) upper limit of normal [ULN] International units per liter [IU/L]); bilirubin (high: >=1.5 * ULN micromoles per liter [µmol/L]); calcium (low: <2 millimoles per liter [mmol/L] \& high: >2.75 mmol/L); glucose (low: <3 \& high: >9 mmol/L); potassium (low: <3 \& high: >5.5 mmol/L); sodium (low: <130 \& high: >150 mmol/L) \& Blood Urea Nitrogen (BUN) (high: >=2 * ULN µmol/L). Participants were counted in worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants were counted twice if participant had both values that changed 'To Low' \& 'To High'.
Measured: Baseline (Day -1) and up to 40 days
Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline
Urine samples were collected for analysis of cellular casts, granular casts, hyaline casts and red blood cells. WBCs were counted as cells per high-power field (cells/HPF). Participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented. Baseline is defined as Day -1.
Measured: Baseline (Day -1) and up to 40 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Sep 201917 Dec 2019

First posted19 Sep 2019
Study start30 Sep 2019
Primary completion17 Dec 2019
Study completion17 Dec 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hypertension, PulmonaryStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: This is a three-period crossover study
Masking: None (open label)
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04095286
Sponsor's protocol ID: 205019
Status last verified: Jul 2020
First submitted: 18 Sep 2019
Last updated: 6 Aug 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH

All Hypertension, Pulmonary trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Randomized Three Period Cross-over Relative Bioavailability Study to Compare the Pharmacokinetic Parameters of a Lower Dose Formulation of Ambrisentan (GSK1325760) With Marketed Ambrisentan in Healthy Adult Participants
ClinicalTrials.gov ID: NCT04095286
Acronym / sponsor ID: 205019
Conditions: Hypertension, Pulmonary
Keywords: Ambrisentan, Oral dosage forms, Pulmonary arterial hypertension, Bioavailability
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 30 Sep 2019 (actual)
Primary completion: 17 Dec 2019 (actual)
Study completion: 17 Dec 2019 (actual)
First posted: 19 Sep 2019 (actual)
Results: Posted 6 Aug 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 6
Model description: This is a three-period crossover study

Arm	Type	Receives
AMB dispersed in water/AMB oral tablet/reference AMB	Experimental	Drug: AMB new formulation (1 mg), Drug: Reference AMB (5 mg)Eligible participants will receive a single oral dose of 5 milligram (mg) AMB tablet dispersed in water during treatment period 1 followed by a single dose of 5 mg AMB oral tablet in treatment period 2. In treatment period 3, participants will receive a single oral dose of reference 5 mg AMB tablet. There will be a washout period of 7 days between doses in each treatment period.
AMB oral tablet/reference AMB/AMB dispersed in water	Experimental	Drug: AMB new formulation (1 mg), Drug: Reference AMB (5 mg)Eligible participants will receive single dose of 5 mg AMB oral tablet during treatment period 1 followed by single dose of reference 5 mg AMB oral tablet in treatment period 2. In treatment period 3, participants will receive single dose of 5 mg AMB tablet dispersed in water. There will be a washout period of 7 days between doses in each treatment period.
Reference AMB/AMB dispersed in water/AMB oral tablet	Experimental	Drug: AMB new formulation (1 mg), Drug: Reference AMB (5 mg)Eligible participants will receive single dose of reference 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB tablet dispersed in water in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period.
AMB dispersed in water/reference AMB/AMB oral tablet	Experimental	Drug: AMB new formulation (1 mg), Drug: Reference AMB (5 mg)Eligible participants will receive single dose of 5 mg AMB tablet dispersed in water during treatment period 1 followed by single dose of reference 5 mg AMB oral tablet in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period.
AMB oral tablet/AMB dispersed in water/reference AMB	Experimental	Drug: AMB new formulation (1 mg), Drug: Reference AMB (5 mg)Eligible participants will receive single dose of 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB tablet dispersed in water in treatment period 2. In treatment period 3 participants will receive single dose of reference 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period.
Reference AMB/AMB oral/AMB dispersed in water	Experimental	Drug: AMB new formulation (1 mg), Drug: Reference AMB (5 mg)Eligible participants in this arm will receive single dose of reference 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB oral tablet in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB tablet dispersed in water There will be a washout period of 7 days between doses in each treatment period.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring.
Average systolic blood pressure between 100-160 millimeter of mercury (mmHg) and diastolic between 55-90 mmHg (inclusive) over 3 readings at Screening.
Body weight >=50 kilogram (kg) for men and >= 45kg for women, and body mass index (BMI) within the range 18-30 kilogram per meter square (kg/m^2) (inclusive).
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): 1. Refrain from donating sperm plus either 2. 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

Key exclusion criteria (20 listed)

History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,endocrine, hematological, 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.
History or presence of palpitations or tachyarrhythmia.
Hemoglobin (Hb) below the normal range (Hb <133 grams per liter [g/L] for male participants ; and Hb <114 g/L for female participants).
Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN)
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AMB new formulation (1 mg)AMB tablets will be available at a unit dose strength of 1 mg. Participants will orally administer 5 tablets of 1 mg unit dose.	Drug	AMB dispersed in water/AMB oral tablet/reference AMB, AMB dispersed in water/reference AMB/AMB oral tablet, AMB oral tablet/AMB dispersed in water/reference AMB, AMB oral tablet/reference AMB/AMB dispersed in water, Reference AMB/AMB dispersed in water/AMB oral tablet, Reference AMB/AMB oral/AMB dispersed in water
Reference AMB (5 mg)AMB reference tablet will be available as film-coated tablet at unit dose strength of 5 mg. Participants will orally administer 1 tablet of 5 mg unit dose	Drug	AMB dispersed in water/AMB oral tablet/reference AMB, AMB dispersed in water/reference AMB/AMB oral tablet, AMB oral tablet/AMB dispersed in water/reference AMB, AMB oral tablet/reference AMB/AMB dispersed in water, Reference AMB/AMB dispersed in water/AMB oral tablet, Reference AMB/AMB oral/AMB dispersed in water

Primary outcome

Maximum Observed Plasma Concentration (Cmax) After Administration of AMB Under Fasted Condition
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who provided PK parameter data.
Time to Cmax (Tmax) After Administration of AMB Under Fasted Condition
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.
Time of Last Quantifiable Concentration (Tlast) After Administration of AMB Under Fasted Condition
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [(AUC(0-inf)] After Administration of AMB Under Fasted Condition
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.
Area Under the Plasma Concentration-time Curve From Time Zero to Last Time of Quantifiable Concentration [AUC(0-t)] After Administration of AMB Under Fasted Condition
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.
Apparent Terminal Phase Half-life (t1/2) After Administration of AMB Under Fasted Condition
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose
Blood samples were collected at indicated time-points for PK analysis of AMB. PK parameters were calculated by standard non-compartmental analysis.

6 secondary outcomes

Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=2%)
Time frame: Up to 40 days
Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: Baseline (Day 1) and up to 40 days
Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Time frame: Baseline (Day 1) and up to 40 days
Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Time frame: Baseline (Day -1) and up to 40 days
Number of Participants With Worst Case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline
Time frame: Baseline (Day -1) and up to 40 days
Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline
Time frame: Baseline (Day -1) and up to 40 days

Results and safety

Results posted to the registry on 6 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AMB Dispersed in Water/AMB Oral Tablet/Reference AMB	4	3
AMB Oral Tablet/Reference AMB/AMB Dispersed in Water	5	4
Reference AMB/AMB Dispersed in Water/AMB Oral Tablet	5	4
AMB Dispersed in Water/Reference AMB/AMB Oral Tablet	5	5
AMB Oral Tablet/AMB Dispersed in Water/Reference AMB	5	5
Reference AMB/AMB Oral/AMB Dispersed in Water	5	5

Primary outcome: Maximum Observed Plasma Concentration (Cmax) After Administration of AMB Under Fasted Condition

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: Nanogram per milliliter

Measure	AMB Dispersed in Water n = 27	AMB Oral Tablet n = 25	Reference AMB n = 26
Value	359.030 (15.5)	316.505 (19.2)	353.252 (29.3)

AMB Dispersed in Water vs Reference AMB: Ratio of adjusted geometric mean: 1.03 (90% CI 0.96 to 1.11)
AMB Oral Tablet vs Reference AMB: Ratio of adjusted geometric mean: 0.91 (90% CI 0.85 to 0.98)

Population analysed: PK Parameter Population. Only those participants with data available at the specified data points were analyzed.

Primary outcome: Time to Cmax (Tmax) After Administration of AMB Under Fasted Condition

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose. Median (Full Range). Unit: Hour

Measure	AMB Dispersed in Water n = 27	AMB Oral Tablet n = 25	Reference AMB n = 26
Value	1.000 (0.50 to 2.00)	2.000 (1.00 to 4.00)	1.750 (0.50 to 8.00)

Population analysed: PK Parameter Population. Only those participants with data available at the specified data points were analyzed.

Primary outcome: Time of Last Quantifiable Concentration (Tlast) After Administration of AMB Under Fasted Condition

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose. Median (Full Range). Unit: Hour

Measure	AMB Dispersed in Water n = 27	AMB Oral Tablet n = 25	Reference AMB n = 26
Value	72.00 (71.5 to 72.4)	72.00 (71.5 to 72.1)	72.00 (71.5 to 72.2)

Population analysed: PK Parameter Population. Only those participants with data available at the specified data points were analyzed.

Primary outcome: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [(AUC(0-inf)] After Administration of AMB Under Fasted Condition

Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: Hours*nanogram per milliliter

Measure	AMB Dispersed in Water n = 23	AMB Oral Tablet n = 19	Reference AMB n = 22
Value	3006.443 (23.6)	2859.283 (21.7)	2963.908 (21.6)

AMB Dispersed in Water vs Reference AMB: Ratio of adjusted geometric mean: 1.05 (90% CI 1.02 to 1.09)
AMB Oral Tablet vs Reference AMB: Ratio of adjusted geometric mean: 1.04 (90% CI 1.00 to 1.08)

Population analysed: PK Parameter Population. Only those participants with data available at the specified data points were analysed.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: SAEs and non-SAEs were collected from the start of study treatment until the follow up (Up to 40 days). Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AMB Dispersed in Water	0 of 27 (0%)	5 of 27 (18.5%)	0 of 27
AMB Oral Tablet	0 of 25 (0%)	7 of 25 (28%)	0 of 25
Reference AMB	0 of 26 (0%)	5 of 26 (19.2%)	0 of 26

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

Related trials for Hypertension, Pulmonary

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AMB new formulation (1 mg) and Reference AMB (5 mg) in people with Hypertension, Pulmonary, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Plasma Concentration (Cmax) After Administration of AMB Under Fasted Condition (time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 18, 24, 36, 48 and 72 hours post-dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04095286.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2020.