AzTrials
AzTrials

Hypertension, PulmonaryPhase 2NCT03177603

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

A Phase 2 study testing GSK2586881 in people with Hypertension, Pulmonary, run by GlaxoSmithKline at 8 sites in 3 countries.

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

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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hypertension, Pulmonary
What is being tested?
GSK2586881
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
8 sitesin 3 countries
Study dates
21 Feb 2018to 7 May 2019
Phase
Phase 2
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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.

Who cannot join

  • 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).
Show all 23Show fewer
  • 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.

Trial locations and contacts

8 sites in 3 countries.

8 sites in 3 countries

Germany4 sites

  • GSK Investigational Site

    Berlin, 14050

  • GSK Investigational Site

    Cologne, North Rhine-Westphalia, 50937

  • GSK Investigational Site

    Dresden, Saxony, 01307

  • GSK Investigational Site

    Heidelberg, Baden-Wurttemberg, 69126

Other trials in Germany

United States2 sites

  • GSK Investigational Site

    Dallas, Texas, 75390-8550

  • GSK Investigational Site

    Pittsburgh, Pennsylvania, 15213

Other trials in United States

Spain2 sites

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Madrid, 28041

Other trials in Spain

About this study

Official 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

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.

Being tested
GSK2586881
Keywords
Pulmonary Arterial Hypertension, Dose-escalation, Safety, Tolerability, GSK2586881
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.

  • GSK2586881Drug

    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.

Study groups in NCT03177603
Study groupRoleWhat they receive
GSK2586881 - 0.1 mg/kgExperimentalEligible subjects will receive a single dose of 0.1 mg/kg GSK2586881. Dose escalation up to maximum dose of 0.8 mg/kg 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.
Receives: Drug: GSK2586881
GSK2586881 - 0.2 mg/kgExperimentalEligible subjects will receive a single dose 0.2 mg/kg of GSK2586881 IV infusion. Dose escalation up to maximum dose of 0.8 mg/kg 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.
Receives: Drug: GSK2586881
GSK2586881 - 0.4 mg/kgExperimentalEligible subjects will receive a single dose of 0.4 mg/kg of GSK2586881 IV infusion. Dose escalation up to maximum dose of 0.8 mg/kg 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.
Receives: Drug: GSK2586881
GSK2586881 - 0.8 mg/kgExperimentalEligible subjects will receive single dose of 0.8 mg/kg of GSK2586881 IV infusion. 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.
Receives: Drug: GSK2586881

What is being measured

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

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

    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.

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

  2. Change From Baseline in Cardiac Output (CO)

    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.

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

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

    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.

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

Secondary outcomes (36)

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

    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.

    Measured: Up to Day 28

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

    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.

    Measured: Up to Day 28

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

  8. Change From Baseline in Hematology Parameter: Hemoglobin

    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.

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

  9. Change From Baseline in Hematology Parameter: Hematocrit

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

  13. Change From Baseline in Hematology Parameter: Reticulocytes

    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.

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

  14. Number of Participants With Urinalysis Results by Dipstick Method

    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.

    Measured: 24 hours post-dose (Day 1)

  15. Change From Baseline in Pulse Rate

    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.

    Measured: 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)

  16. Change From Baseline in Respiratory Rate

    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.

    Measured: 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)

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

    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.

    Measured: 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)

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

    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.

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

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

    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.

    Measured: 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)

  20. Number of Participants With Positive Immunogenicity Results

    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.

    Measured: Up to Day 28

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

    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.

    Measured: 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)

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

    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.

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

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

    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.

    Measured: 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)

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

  28. Maximum Observed Plasma Concentration (Cmax) of GSK2586881

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

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

  29. Time to Cmax (Tmax) of GSK2586881

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

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

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

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

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

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

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

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

  32. Last Observed Quantifiable Concentration (Ct) of GSK2586881

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

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

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

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

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

  34. Plasma Clearance (CL) of GSK2586881

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

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

  35. Apparent Volume of Distribution of GSK2586881

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

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

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

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

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

Timeline

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

  1. First posted6 Jun 2017
  2. Study start21 Feb 2018
  3. Primary completion7 May 2019
  4. Study completion7 May 2019

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03177603
Sponsor's protocol ID
206246
Other IDs
2017-000212-41, 2017
Status last verified
Mar 2020
First submitted
23 May 2017
Last updated
21 Apr 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK2586881 in people with Hypertension, Pulmonary, run by GlaxoSmithKline at 8 sites in 3 countries.

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 12 inclusion and 23 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 21 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Germany, United States, Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 21 Apr 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?

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)). The study lists 3 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 NCT03177603.

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 21 Apr 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in