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A Dose-escalation Study in Subjects With Pulmonary Arterial Hypertension (PAH) | Clinical Trials | Clareo Health

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

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

NCT03177603•GlaxoSmithKline

View on ClinicalTrials.gov

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 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.

Eligibility

Age

18 - 75 years

Sex

ALL

Healthy Volunteers

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).
+2 more criteria

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.
+13 more criteria

Locations (8)

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Berlin, Germany

GSK Investigational Site

Barcelona, Spain

GSK Investigational Site

Madrid, Spain

Key Dates

Start Date

February 21, 2018

Primary Completion Date

May 7, 2019

Completion Date

May 7, 2019

Last Updated

April 21, 2020

Enrollment

ACTUAL participants

Conditions

Hypertension, Pulmonary

Interventions

GSK2586881

DRUG

A Deep-Learning-Enabled Electrocardiogram for Detecting Pulmonary Hypertension

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RECRUITINGNA

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Hypertension, PulmonaryPulmonary Thromboembolisms

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: April 21, 2020Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

A Deep-Learning-Enabled Electrocardiogram for Detecting Pulmonary Hypertension

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