Measuring Outcomes In Patients With Pulmonary Arterial Hypertension Not on Active Treatment (MOTION)

Study Overview
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Brief Summary
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The MOTION study was a prospective, Phase IV study for patients with Pulmonary Arterial Hypertension (PAH). The study was designed to further explore patient-reported outcomes in PAH subjects who were not on active treatment and living in the United States. In addition, the study explored the use of new telemetric technology (Accelerator band) to evaluate if this technology correlates with improvements in 6 Minute Walking Distance 6MWD in patients with PAH.

Official Title
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A Phase IV, Prospective, Single-Arm, Open-Label Study to Measure Outcomes in Patients With Pulmonary Arterial Hypertension Not on Active Treatment

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Drug: Riociguat (Adempas, BAY63-2521)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, 18 to 80 years of age at Visit 0 Women of childbearing potential must have a negative pre-treatment pregnancy test, negative monthly pregnancy test, and must use reliable methods of contraception according to the Risk Evaluation Mitigation Strategies (REMS) guidance Symptomatic pulmonary arterial hypertension, World Health Organization Group 1 with a pulmonary vascular resistance (PVR) >300 dyn*sec*cm-5, mean pulmonary artery pressure (PAP mean) ≥25 mmHg, and pulmonary capillary wedge pressure (PCWP) ≤15 mmHg as assessed by right heart catheterization within 6 months prior to Screening (Visit 0) PAH of the following types: Idiopathic (IPAH) Familial (FPAH) Associated with PAH (APAH) due to: Connective tissue disease Congenital heart disease, but only if patient underwent surgical repair more than one year before enrollment Anorexigen or amphetamine use Portal hypertension with liver cirrhosis Not treated with PAH-specific pulmonary medications within 14 days of Screening (Visit 0) 6MWD between 150 meters and 450 meters Exclusion Criteria: Patients who are pregnant Patients currently on nitrate and/or nitric oxide (NO) donor therapy; patients currently taking phosphodiesterase 5 (PDE5) inhibitors (such as sildenafil, tadalafil, vardenafil) and non-specific PDE inhibitors (theophylline, dipyridamole) Non-WHO group 1 Pulmonary Hypertension Severe restrictive lung disease History of uncontrolled high blood pressure or hypotension A medical disorder, condition, or history that in the opinion of the Investigator would impair their ability to participate or complete this study Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Riociguat 0.5mg to 2.5 mg<br>Single arm, open label | Drug: Riociguat (Adempas, BAY63-2521)<br>* Participants received therapy with riociguat during a 10-week titration phase. The starting dose for riociguat for all patients was 0.5 milligram (mg) three times a day (TID). The dose of riociguat was increased every 2 weeks in 0.5 mg increments to 1.0, 1.5, 2.0, and 2.5 mg until patients reached their individual optimal dose based on their systolic blood pressure and well-being. After reaching their optimal dose, patients then entered a maintenance phase and remained on this dose for an additional 14 weeks. End of treatment was reached at Visit 10 after 24 weeks of treatment with riociguat.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 24 in the Living With Pulmonary Hypertension (LPH) Questionnaire Total Score | The Living with Pulmonary Hypertension (LPH) questionnaire with Heart Failure questionnaire comprises 21 items, responded to on a 6-point Likert scale ranging from 0 'No' to 5 'Very much'. A total score ranging from 0 (best) to 105 (worst) is calculated by summing the responses to all 21 questions. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Weeks 4 and 16 in the LPH Total Score | The Living with Pulmonary Hypertension (LPH) questionnaire with Heart Failure questionnaire comprises 21 items, responded to on a 6-point Likert scale ranging from 0 'No' to 5 'Very much'. A total score ranging from 0 (best) to 105 (worst) is calculated by summing the responses to all 21 questions. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Baseline to Week 4 and Week 16 | 
| Change From Week 16 to Week 24 in the LPH Total Score (Completers Analysis Set Only) | The Living with Pulmonary Hypertension (LPH) questionnaire with Heart Failure questionnaire comprises 21 items, responded to on a 6-point Likert scale ranging from 0 'No' to 5 'Very much'. A total score ranging from 0 (best) to 105 (worst) is calculated by summing the responses to all 21 questions. | Week 16 to Week 24 | 
| Change From Baseline to Weeks 4, 16, and 24 in the LPH Physical Dimension Score | The LPH derived from the Minnesota Living with Heart Failure questionnaire comprises 21 items, responded to on a 6-point Likert scale ranging from 0 'No' to 5 'Very much'. A total score ranging from 0 to 105 is calculated by summing the responses to all 21 questions. A physical dimension score (range 0-40, 8 items) and an emotional dimension score (range 0-25, 5 items) can also be calculated. For all LPH scores, a higher score indicates that patients are more affected by their medical condition. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Baseline to Weeks 4, 16, and 24 | 
| Change From Week 16 to Week 24 in the LPH Physical Dimension Score (Completers Analysis Set Only) | The LPH derived from the Minnesota Living with Heart Failure questionnaire comprises 21 items, responded to on a 6-point Likert scale ranging from 0 'No' to 5 'Very much'. A total score ranging from 0 to 105 is calculated by summing the responses to all 21 questions. A physical dimension score (range 0-40, 8 items) and an emotional dimension score (range 0-25, 5 items) can also be calculated. For all LPH scores, a higher score indicates that patients are more affected by their medical condition. | Week 16 to Week 24 | 
| Change From Baseline to Weeks 4, 16, and 24 in the LPH Emotional Dimension Score | The LPH derived from the Minnesota Living with Heart Failure questionnaire comprises 21 items, responded to on a 6-point Likert scale ranging from 0 'No' to 5 'Very much'. A total score ranging from 0 to 105 is calculated by summing the responses to all 21 questions. A physical dimension score (range 0-40, 8 items) and an emotional dimension score (range 0-25, 5 items) can also be calculated. For all LPH scores, a higher score indicates that patients are more affected by their medical condition. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Baseline to Week 4, Week 16 and Week 24 | 
| Change From Week 16 to Week 24 in the LPH Emotional Dimension Score (Completers Analysis Set Only) | The LPH derived from the Minnesota Living with Heart Failure questionnaire comprises 21 items, responded to on a 6-point Likert scale ranging from 0 'No' to 5 'Very much'. A total score ranging from 0 to 105 is calculated by summing the responses to all 21 questions. A physical dimension score (range 0-40, 8 items) and an emotional dimension score (range 0-25, 5 items) can also be calculated. For all LPH scores, a higher score indicates that patients are more affected by their medical condition. | Week 16 to Week 24 | 
| Percentage of Patients With a Minimal Clinically Significant Important Difference (MCID) From Baseline in LPH Total Score at Weeks 4, 16, and 24 | For LPH total score, the MCID was an 11-point decrease from baseline. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Baseline to Week 4, Week 16 and Week 24 | 
| Percentage of Patients With an MCID From Baseline in LPH Physical Dimension Score at Weeks 4, 16, and 24 | For the physical and emotional dimension scores, the MCID was a 4-point decrease. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Baseline to Week 4, Week 16 and Week 24 | 
| Percentage of Patients With an MCID From Baseline in LPH Emotional Dimension Score at Weeks 4, 16, and 24 | For the physical and emotional dimension scores, the MCID was a 4-point decrease. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Baseline to Week 4, Week 16 and Week 24 | 
| Percentage of Patients With an MCID From Week 16 in LPH Total Score at Week 24 (Completers Analysis Set Only) | For LPH total score, the MCID was an 11-point decrease. | Week 16 to Week 24 | 
| Percentage of Patients With an MCID From Week 16 in Physical Dimension Score at Week 24 (Completers Analysis Set Only) | For the physical and emotional dimension scores, the MCID was a 4-point decrease. | Week 16 to Week 24 | 
| Percentage of Patients With an MCID From Week 16 in Emotional Dimension Score at Week 24 (Completers Analysis Set Only) | For the physical and emotional dimension scores, the MCID was a 4-point decrease. | Week 16 to Week 24 | 
| Change From Baseline to Weeks 4, 16, and 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands and Output Demands Scores | The Work Limitations Questionnaire (WLQ) is an 8-item questionnaire that measures the degree to which employed individuals are experiencing limitations on-the-job due to their health problems, and health-related productivity loss (Presenteeism). The WLQ's terms are aggregated into four scales (i.e. Time Management, Physical demands, Mental-interpersonal demands, Output demands). Scale score range from 0 (limited none of the time) to 100 (limited all of the time) and represent the reported amount of time in the prior two weeks respondents were limited on-the-job. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Baseline to Week 4, Week 16 and Week 24 | 
| Change From Baseline to Weeks 4, 16, and 24 in the WLQ Percentage of Productivity Loss | The WLQ is an 8-item questionnaire that measures the degree to which employed individuals are experiencing limitations on-the-job due to their health problems, and health-related productivity loss (Presenteeism). The WLQ's terms are aggregated into four scales (i.e. Time Management, Physical demands, Mental-interpersonal demands, Output demands). Using an algorithm, WLQ scale scores can be converted into an estimate of productivity loss. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Baseline to Week 4, Week 16 and Week 24 | 
| Change From Week 16 to Week 24 in the WLQ Time Management, Physical Demands, Mental-Interpersonal Demands, and Output Demands Scores (Completers Analysis Set Only) | The Work Limitations Questionnaire (WLQ) is an 8-item questionnaire that measures the degree to which employed individuals are experiencing limitations on-the-job due to their health problems, and health-related productivity loss (Presenteeism). The WLQ's terms are aggregated into four scales (i.e. Time Management, Physical demands, Mental-interpersonal demands, Output demands). Scale score range from 0 (limited none of the time) to 100 (limited all of the time) and represent the reported amount of time in the prior two weeks respondents were limited on-the-job. | Week 16 to Week 24 | 
| Change From Week 16 to Week 24 in the WLQ Percentage of Productivity Loss (Completers Analysis Set Only) | The WLQ is an 8-item questionnaire that measures the degree to which employed individuals are experiencing limitations on-the-job due to their health problems, and health-related productivity loss (Presenteeism). The WLQ's terms are aggregated into four scales (i.e. Time Management, Physical demands, Mental-interpersonal demands, Output demands). Using an algorithm, WLQ scale scores can be converted into an estimate of productivity loss. | Week 16 to Week 24 | 
| Change From Baseline to Weeks 4, 16, and 24 in the Short Form-12 Health Survey (SF-12) Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score | SF-12v2® Health Survey is a 12-item questionnaire to measure functional health and well-being from the patient's point of view. Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Baseline to Week 4, Week 16 and Week 24 | 
| Change From Week 16 to Week 24 in the SF-12 PCS Score and MCS Score (Completers Analysis Set Only) | SF-12v2® Health Survey is a 12-item questionnaire to measure functional health and well-being from the patient's point of view. Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. | Week 16 to Week 24 | 
| Change From Baseline to Weeks 4, 16, and 24 in the WHO Functional Class | Functional class was determined by the WHO classification: I: Patients with PH (pulmonary hypertension) but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. II: Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. III: Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. IV: Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Baseline to Week 4, Week 16 and Week 24 | 
| Change From Week 16 to Week 24 in the WHO Functional Class (Completers Analysis Set Only) | Functional class was determined by the WHO classification: I: Patients with PH (pulmonary hypertension) but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. II: Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. III: Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. IV: Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity. | Week 16 to Week 24 | 
| Change From Baseline to Weeks 16 and 24 in the Modified Borg Dyspnea Scale | The Modified Borg Dyspnea Scale assessed the intensity of the patient's dyspnea from 0 (best) to 10 (worst). In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Week 16 to Week 24 | 
| Change From Week 16 to Week 24 in the Modified Borg Dyspnea Scale (Completers Analysis Set Only) | The Modified Borg Dyspnea Scale assessed the intensity of the patient's dyspnea from 0 (best) to 10 (worst). | Week 16 to Week 24 | 
| Change From Baseline to Weeks 16 and 24 in the 6MWD | Six-minute walk distance (6MWD) was conducted to test the physical limitations of the patient by assessing the patient's exercise capacity. The distance walked by the patient in 6 minutes was measured. In the below table, N signifies subjects who were evaluable for the specific parameter at that timepoint. | Week 16 to Week 24 | 
| Change From Week 16 to Week 24 in the 6MWD (Completers Analysis Set Only) | Six-minute walk distance (6MWD) was conducted to test the physical limitations of the patient by assessing the patient's exercise capacity. The distance walked by the patient in 6 minutes was measured. | Week 16 to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Hypertension,Riociguat,Living with Pulmonary Hypertension Questionnaire