Skip to main content
OpenTrials
Completed

NCT Number: NCT03177603

A Dose-escalation Study in Subjects With Pulmonary Arterial Hypertension (PAH)

GSK2586881, a purified intravenous (IV) formulation of soluble recombinant human Angiotensin Converting Enzyme (rhACE2) is being investigated as a treatment for PAH. This GlaxoSmithKline (GSK) study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK2586881 in subjects with PAH. This open-label, dose-escalation study will comprise of 4 separate groups based on the planned dose range, and subjects in each group will be administered a single dose of GSK2586881 ranging between 0.1, 0.2, 0.4 and 0.8 milligram per kilogram (mg/kg) via IV route. Dose escalation will occur after 4 subjects have been dosed per cohort and review of safety, tolerability, PK and hemodynamic data up to 24 hours post dose has taken place. A maximum of 27 subjects will be included in the study and the total duration of the study will be up to a maximum of 59 days.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

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

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

GSK Investigational Site, Heidelberg, Baden-Wurttemberg, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Subjects must be between 18-75 years of age (inclusive), at the time of signing the informed consent.
  • Documented diagnosis of PAH, defined as mPAP > 25 millimeter of mercury (mmHg) and pulmonary wedge pressure (PWP) <= 15.
  • Idiopathic PAH (IPAH), Hereditary PAH (HPAH), or PAH associated with collagen vascular disease, or appetite suppressant use.
  • World Health Organization (WHO) functional class I, II, or III, stable for at least 8 weeks prior to enrollment.
  • Hemodynamically stable on background therapy with no evidence of uncontrolled right heart failure (historic data), as determined by the investigator.
  • Six minute walk (6MW) distance, as performed at screening or within 6 months prior to screening, of >= 100 meters (m) and <= 500 m.
  • Mean BP of >60 mmHg.
  • Receiving stable doses of one or more medications that are approved for treatment of PAH, including endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and/or prostanoids/prostacyclin receptor agonists, for a minimum of 12 consecutive weeks before enrollment.
  • Diuretic dose stable for 8 weeks.
  • Body weight <= 100 kg and body mass index (BMI) within the range 18-35 kg per m square (kg/m^2) (inclusive).
  • Male and/or female (following confirmation of negative pregnancy test for Women of Childbearing Potential [WOCBP]). Women who are pregnant or breastfeeding are excluded.
  • Capable of giving signed informed consent.

Exclusion criteria

  • History of systemic hypotension, defined as systolic BP <90 mmHg and/or diastolic BP <50 mmHg.
  • Hospitalization for PAH associated deterioration in the previous 6 months.
  • Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities. Concurrent disease or condition that may interfere with study participation or safety include bleeding disorders, arrhythmia, organ transplant, organ failure, current neoplasm, poorly controlled diabetes mellitus, and serious neurological disorders.
  • Complex repaired and unrepaired congenital heart disease.
  • Subjects with Eisenmenger physiology.
  • Alanine transferase (ALT) >2x upper limit of normal (ULN).
  • Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Estimated glomerular-filtration-rate (eGFR) <45 milliliter per minute per 1.73 meter square (mL/min/1.73m^2).
  • QTc >480 millisecond (msec) or QTc > 500 msec in subjects with bundle branch block.
  • Any bleeding concerns as evidenced by International normalized ratio (INR) >1.5 (in subjects not receiving anticoagulation therapy) or platelet count <80,000.
  • Hemoglobin (Hb) <10 gram per deciliter (g/dL).
  • Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates participation in the study.
  • Any use of an Angiotensin-converting enzyme (ACE) inhibitor or Angiotensin receptor blocker or renin inhibitors within 14 days prior to dosing. Therapy can be stopped to enable inclusion if deemed safe by the subject's treating physician.
  • Use of any investigational product (IP) or device within 30 days prior to dosing, or known requirement for any investigational agent prior to completion of all scheduled study assessments.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Presence of Hepatitis B surface antigen (HBsAg) at screening.
  • Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment.
  • Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
  • Participation in the study would result in loss of blood or blood products in excess of 300mL within 65 days.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • A known or suspected history of alcohol or drug abuse within the 2 years prior to screening.
  • Unable to refrain from smoking during the in-house treatment period.

Treatment and study plan

GSK2586881

Drug

GSK2586881 is a clear colorless liquid for IV infusion over 3- 5 minutes and will be administered a maximum dose of 0.8 mg/kg.

Primary outcomes

  1. Change From Baseline in Pulmonary Vascular Resistance (PVR)

    Time frame: Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

    PVR is the resistance generated by pulmonary circulation. Pulmonary arterial catheters were placed in participants and PVR values were recorded from the right heart catheterization. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

  2. Change From Baseline in Cardiac Output (CO)

    Time frame: Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

    CO is the amount of blood pumped by the heart per minute. Pulmonary arterial catheters were placed in participants and CO values were recorded from the right heart catheterization. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

  3. Change From Baseline in Mean Pulmonary Artery Pressure (mPAP)

    Time frame: Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

    The pulmonary artery pressure is a measure of the blood pressure found in the main pulmonary artery. Pulmonary arterial catheters were placed in participants and mPAP values were recorded from the right heart catheterization. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

Secondary outcomes

  1. Number of Participants With Non-serious Adverse Events (AEs)

    Time frame: Up to Day 28

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

  2. Number of Participants With Serious Adverse Events (SAEs)

    Time frame: Up to Day 28

    Any untoward event resulting in death, life threatening, requiring hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention were categorized as SAE.

  3. Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase and Aspartate Amino Transferase

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of clinical chemistry parameters: alkaline phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  4. Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of clinical chemistry parameters: direct bilirubin, total bilirubin and creatinine. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  5. Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of clinical chemistry parameters: calcium, glucose, potassium, sodium and BUN. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  6. Change From Baseline in Clinical Chemistry Parameter: Total Protein

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of clinical chemistry parameter, total protein. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  7. Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils (T.neutrophils), platelet count and WBC count. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  8. Change From Baseline in Hematology Parameter: Hemoglobin

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of hematology parameter, hemoglobin. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  9. Change From Baseline in Hematology Parameter: Hematocrit

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of hematology parameter, hematocrit. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  10. Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of hematology parameter, mean corpuscle hemoglobin. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  11. Change From Baseline in Hematology Parameter: Mean Corpuscle Volume

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of hematology parameter, mean corpuscle volume. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  12. Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of hematology parameter: RBC count. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  13. Change From Baseline in Hematology Parameter: Reticulocytes

    Time frame: Baseline (Day 1, Pre-dose), 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected for the assessment of hematology parameter: reticulocytes. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  14. Number of Participants With Urinalysis Results by Dipstick Method

    Time frame: 24 hours post-dose (Day 1)

    Urine samples were collected to assess urine bilirubin, urine occult blood, urine glucose, urine ketones, and urine protein by dipstick test. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine bilirubin, urine occult blood, urine glucose, urine ketones and urine protein can be read as negative, trace, 1+, 2+ and 3+ indicating proportional concentrations in the urine sample.

  15. Change From Baseline in Pulse Rate

    Time frame: Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)

    Pulse rate was measured in supine position after at least a 5-minute rest. Change from Baseline in pulse rate was evaluated. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  16. Change From Baseline in Respiratory Rate

    Time frame: Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)

    Respiratory rate was measured in supine position after at least a 5-minute rest. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  17. Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

    Time frame: Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)

    DBP and SBP were measured in supine position after at least a 5-minute rest. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  18. Number of Participants With Abnormal Electrocardiogram (ECG) Findings

    Time frame: 4 hours and 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    12-lead ECGs were obtained at each time point using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and Corrected QT (QTc) intervals. Only those participants who had any abnormal ECG findings are presented. Abnormal ECG findings were categorized as clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings. CS abnormal 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. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  19. Change From Baseline in Pulse Oximetry Parameter: Percent Oxygen in Blood

    Time frame: Baseline (Day 1, Pre-dose); 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)

    Percent oxygen in blood was measured using pulse oximetry after the participant had rested for at least 5 minutes. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  20. Number of Participants With Positive Immunogenicity Results

    Time frame: Up to Day 28

    Immunogenicity samples were collected into a serum-separating tube, mixed by gentle inversion 5 times and left to coagulate at room temperature for a minimum of 30 minutes and a maximum of 60 minutes. All samples were first tested for anti-angiotensin converting enzyme type 2 (ACE2) binding antibodies by screening and confirmation assay steps. If post-dose samples were found to be positive for anti-ACE2 binding antibodies, they would have been further characterized for anti-ACE2 neutralizing antibodies. Number of participants with positive immunogenicity results post-dosing are presented.

  21. Change From Baseline in Systemic Renin-Angiotensin System (RAS) Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)

    Time frame: Baseline (Day 1, Pre-dose); 0.08 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1); and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected to evaluate systemic RAS peptides: Angiotensin (Ang) II, Ang (1-7) and Ang (1-5). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  22. Change From Baseline in Pulmonary Wedge RAS Peptides: Angiotensin II, Angiotensin (1-5) and Angiotensin (1-7)

    Time frame: Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

    Blood samples were collected to evaluate pulmonary wedge RAS peptides: Ang II, Ang (1-5) and Ang (1-7). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

  23. Systemic RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points

    Time frame: 0.08 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, 8 hours and 24 hours post-dose (Day 1) and one sample between Day 7 to Day 14 (follow up visit)

    Blood samples were collected to assess systemic RAS peptides: Angiotensin II and Angiotensin (1-7). Data for angiotensin II/angiotensin (1-7) ratio is presented. Assessment of follow up visit was conducted between any day of Days 7 to 14.

  24. Pulmonary Wedge RAS Peptide: Angiotensin II/Angiotensin (1-7) Ratio at Indicated Time Points

    Time frame: 1 hour, 2 hours and 4 hours post-dose (Day 1)

    Blood samples were collected to assess pulmonary wedge RAS peptides: Angiotensin II and Angiotensin (1-7). Data for angiotensin II/angiotensin (1-7) ratio is presented.

  25. Change From Baseline in Disease Biomarkers: N-terminal Pro B-type Natriuretic Peptide (NT Pro-BNP)

    Time frame: Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)

    Blood samples were collected at specific time points to evaluate NT pro-BNP, a biomarker of disease activity. NT-pro-BNP is a biomarker of cardiac stress or ventricular workload and decreases as a result of reduced force of contraction if pulmonary blood pressure is reduced. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

  26. Change From Baseline in Nitrite, Nitrate and Endogenous Nitrite (Biomarkers of Nitric Oxide [NO])

    Time frame: Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)

    Blood samples were collected at specific time points to evaluate levels of nitrite, nitrate and endogenous nitrite (En. nitrite) (biomarkers of NO). Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

  27. Change From Baseline in Disease Biomarker: Cardiac Troponin-I

    Time frame: Baseline (Day 1, Pre-dose); 2 hours, 4 hours and 24 hours post-dose (Day 1)

    Blood samples were collected at specific time points to assess cardiac troponin I. Cardiac troponin I is a biomarker of cardiac stress. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

  28. Maximum Observed Plasma Concentration (Cmax) of GSK2586881

    Time frame: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

    Blood samples were collected at indicated time points for evaluation of Cmax. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  29. Time to Cmax (Tmax) of GSK2586881

    Time frame: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

    Blood samples were collected at indicated time points for evaluation of tmax. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  30. Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK2586881

    Time frame: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

    Blood samples were collected at indicated time points for evaluation of AUC(0-t). Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  31. Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK2586881

    Time frame: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

    Blood samples were collected at indicated time points for evaluation of AUC(0-inf). Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  32. Last Observed Quantifiable Concentration (Ct) of GSK2586881

    Time frame: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

    Blood samples were collected at indicated time points for evaluation of Ct. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  33. Time of the Last Quantifiable Concentration (Tlast) of GSK2586881

    Time frame: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

    Blood samples were collected at indicated time points for evaluation of tlast. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  34. Plasma Clearance (CL) of GSK2586881

    Time frame: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

    Blood samples were collected at indicated time points for evaluation of CL. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  35. Apparent Volume of Distribution of GSK2586881

    Time frame: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

    Blood samples were collected at indicated time points for evaluation of apparent volume of distribution. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  36. Apparent Terminal Phase Half-life (t1/2) of GSK2586881

    Time frame: Pre-dose (Day 1) and 0.08, 0.5, 1, 2, 4, 8 and 24 hours post-dose (Day 1)

    Blood samples were collected at indicated time points for evaluation of t1/2. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Other outcomes

  1. Change From Baseline in Cardiac Index (CI)

    Time frame: Baseline (Day 1, Pre-dose); 1 hour, 2 hours and 4 hours post-dose (Day 1)

    Cardiac index (CI) was measured using thermodilution. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including those from unscheduled visits. Change from Baseline was measured as ratio of post-dose visit value to Baseline value.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

An Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of GSK2586881 in Participants With Pulmonary Arterial Hypertension

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Jun 6, 2017
Registry last updated
Apr 21, 2020

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.

Related clinical trials

Published trials that share one or more normalized conditions with this study.