Pulmonary arterial hypertension MedDRA version: 20.0 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 20.0 Level: LLT Classification code 10077739 Term: Pulmonary arterial hypertension WHO functional class I System
Conditions
Interventions
Product Name: GSK2586881
Product Code: GSK2586881
Pharmaceutical Form: Solution for injection
INN or Proposed INN: GSK2586881
Current Sp
Sponsors
GlaxoSmithKline, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age 1. Participant must be between 18-75 years of age (inclusive), at the time of signing the informed consent Type of Participant and Disease Characteristics 2. Documented diagnosis of PAH, defined as mPAP > 25 mmHg and PWP = 15 mmHg. 3. IPAH, HPAH, or PAH associated with collagen vascular disease, repaired congenital heart disease, or appetite suppressant use. - Note: Those with portopulmonary hypertension or PVOD are not eligible for the study 4. World Health Organization (WHO) functional class I, II, or III, stable for at least 8 weeks prior to enrollment. 5. Hemodynamically stable on background therapy without evidence of right heart failure (historic data). 6. Six minute walk (6MW) distance, as performed at screening or within 6 months prior to screening, of > 100 meters 7. Mean BP of >60 mmHg 8. 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. NOTE: Anticoagulant therapy can be adjusted according to target INR 9. Diuretic dose stable for 8 weeks. Weight 10. Body weight =65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. History of systemic hypotension, defined as systolic BP 2x upper limit of normal (ULN). 7. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 480 msec or QTc > 500 msec in participants with bundle branch block. NOTES: -The QTc is the QT interval corrected for heart rate according to Bazett’s formula (QTcB), Fridericia’s formula (QTcF), and/or another method. It is either machineread or manually over-read. -The specific formula used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study. In other words, several different formulas cannot be used to calculate the QTc for an individual participant and then the lowest QTc value used to include or discontinue the participant from the trial. 11. Any bleeding concerns as evidenced by INR >1.5 (in participants not receiving anticoagulation therapy) or platelet count <80,000. 12. Hb <10 g/dL Prior/Concomitant Therapy 13. 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. 14. Any use of an ACE inhibitor or angiotensin receptor blocker within 14 days prior to dosing. Therapy can be stopped to enable inclusion if deemed safe by the participant’s treating physician. Prior/Concurrent Clinical Study Experience 15. 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. Diagnostic assessments 16. Positive HIV antibody test. 17. Presence of Hepatitis B surface antigen (HBsAg) at screening. 18. Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment. -NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease can be
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate changes in the pulmonary hemodynamics after single IV doses of GSK2586881 administered to participants with PAH receiving background PAH therapy.;Primary end point(s): - Change from baseline in pulmonary vascular resistance (PVR), cardiac output (CO) and mean pulmonary artery pressure (mPAP), as data permit;Timepoint(s) of evaluation of this end point: 0, 1h, 2h, 4h; Secondary Objective: - To evaluate the safety and tolerability of single IV doses of GSK2586881 administered to participants with PAH receiving background PAH therapy. -To evaluate the effect of single IV doses of GSK2586881 on RAS peptide responses in participants with PAH receiving background PAH therapy. -To evaluate the effect on biomarkers of disease activity after single IV doses of GSK2586881 administered to participants with PAH receiving background PAH therapy. -To evaluate the pharmacokinetics of GSK2586881 after single IV doses of GSK2586881 in participants with PAH receiving background PAH therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Adverse events (AE), clinical laboratory values, vital signs, ECG, pulse oximetry and immunogenicity. -Change from baseline of RAS peptides (e.g. Ang II, Ang(1-7), Ang(1-5), transpulmonary gradient of AngII/Ang (1-7) ratio). -Change from baseline in NT pro-BNP, NO and cardiac troponin I. -Plasma concentrations of GSK2586881 and derived PK parameters. ; Timepoint(s) of evaluation of this end point: • 0.08h • 0.5h • 1h • 2h • 4h • 8h • 24h • 7-14 days after dose, • immunogenicity also collected at 28 +/- 3 days after dose | — |
Countries
Germany, Spain, United States
Contacts
Public ContactCentro de Información
GlaxoSmithKline
Outcome results
None listed