Single Dose Study in Patients With Chronic Obstructive Pulmonary Disease (COPD) Associated Pulmonary Hypertension.

Bayer23 enrolled

Overview

This study is to demonstrate the safety, tolerability, pharmakokinetic and pharmacodynamic effect of a single oral dose of BAY63-2521 in patients with pulmonary hypertension due to chronic obstructive pulmonary disease (COPD).

In addition to the pharmacodynamic and pharmacokinetic variables, the following laboratory variables were assessed: * Hematology: Leucocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelets, white blood cell (WBC), partial thromboplastin time (PTT), prothrombin time (Quick), international normalized ratio (INR) (prothrombin time expressed in relation to normal value) ; * Clinical chemistry: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transpeptidase (GGT), creatine phosphokinase (CK), lipase, cholinesterase (CHE), glucose, creatinine, urea, uric acid, bilirubin, total protein, serum albumin, sodium, potassium, calcium, chloride. And due to the small number of subjects analyzed at several local labs, no summary statistics were provided.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hypertension, Pulmonary Pulmonary Disease, Chronic Obstructive

Interventions

Riociguat (Adempas, BAY63-2521) 1.0 mgDRUG

1.0 mg BAY63-2521 will be given twice per subject, as single dose administration during the hemodynamic investigation (on study day 1) and during the lung function testing (on study day 3).

Riociguat (Adempas, BAY63-2521) 2.5 mgDRUG

2.5 mg BAY63-2521 will be given twice per subject, as single dose administration during the hemodynamic investigation (on study day 1) and during the lung function testing (on study day 3).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with pulmonary hypertension due to COPD, undergoing routine invasive measurement of hemodynamic parameters. * Catheters for measurement of hemodynamic parameters (PAP \[pulmonary artery pressure\], PCWP \[pulmonary capillary wedge pressure\], CO \[cardiac output\], SBP \[systolic blood pressure\]) must be in place independent of the trial. Exclusion Criteria: * Acute exacerbation of COPD, * Pre-existing lung disease other than COPD, * Acute or severe chronic left heart failure, * Severe coronary artery disease, * Uncontrolled arterial hypertension; * Severe left ventricular hypertrophy, * Congenital or acquired valvular or myocardial disease, * Systolic blood pressure \< 100 mmHg, * Heart rate \< 55 bpm or \>105 bpm, * PaO2 (arterial partial oxygen pressure)/FiO2 (fraction of inspired oxygen) \< 50 mmHg, * PaCO2 (arterial partial pressure of carbon dioxide) \> 55 mmHg, * Severe hepatic insufficiency, * Severe renal insufficiency.

Locations (7)

Unnamed facility

Heidelberg, Baden-Wurttemberg, Germany

Unnamed facility

Löwenstein, Baden-Wurttemberg, Germany

Unnamed facility

München, Bavaria, Germany

Unnamed facility

Bad Nauheim, Hesse, Germany

Outcomes

Primary Outcomes

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean)

PAPmean was reported during right heart catheterization

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance (PVR)

PVR was calculated according to the formula PVR = 80\*(PAPmean - pulmonary capillary wedge pressure)/cardiac output

Time frame: From baseline up to 4 hours after administration

Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat

Time frame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose

Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat

Time frame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose

Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose Per kg Body Weight (AUCnorm) of Riociguat and Metabolite M1 After Single Dose of Riociguat

Time frame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose

Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat

Time frame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose

Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat

Data from ClinicalTrials.gov

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Secondary Outcomes

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Right Atrial Pressure (RAPmean)

RAPmean was reported during right heart catheterization

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Pulmonary Artery Pressure (PAPsyst)

PAPsyst was acquired during right heart catheterization

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Pulmonary Artery Pressure (PAPdiast)

PAPdiast was acquired during right heart catheterization

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Capillary Wedge Pressure (PCWP)

PCWP was acquired during right heart catheterization

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Heart Rate (HR)

HR was acquired during right heart catheterization

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Blood Pressure (SBP)

Systolic arterial blood pressure was acquired during right heart catheterization.

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Blood Pressure (DBP)

Diastolic arterial blood pressure was acquired during right heart catheterization.

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Arterial Pressure (MAP)

MAP was acquired during right heart catheterization

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Output (CO)

CO was measured in triplicate by the thermodilution technique

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance Index (PVRI)

PVRI was calculated as PVRI = (80\*(PAPmean - PCWP)/CO)\*body surface area

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance (SVR)

SVR was calculated as SVR = 80\*(MAP-RAPmean)/CO

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance Index (SVRI)

SVRI was calculated as SVRI = (80\*(MAP - RAPmean)/CO)\*body surface area

Time frame: From baseline up to 4 hours after administration

Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Index

Cardiac index was calculated as cardiac index = CO / body surface area.

Time frame: From baseline up to 4 hours after administration

Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Oxygen Pressure (PaO2)

Arterial blood gas analysis was performed by insertion of an indwelling arterial cannula. Percent change was calculated as "100%\*(value post dose - value at baseline)/ value at baseline".