Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
influence of bronchodilatation with salmeterol on the autonomic nervous systems in COPD patients will be measured using MSNA., Relation of COPD and sympathetic nerve activity is to be evaluated,
Brief summary
This is a 4-week non-randomized, partially blinded, single-arm monocentre study in subjects with Chronic Obstructive Pulmonary Disease (COPD) Global Initiative for Chronic Obstructive Lung Disease (GOLD) class II or III with the aim to demonstrate that inhaled therapy with salmeterol reduces sympathetic activity as evaluated by microneurography. A maximum of 32 subjects is planned to be enrolled.
Detailed description
This is a 4-week non-randomized, partially blinded, single-arm monocentre study in subjects with COPD GOLD class II or III with the aim to demonstrate that inhaled therapy with salmeterol reduces sympathetic activity as evaluated by microneurography. A maximum of 32 subjects is planned to be enrolled. During a complex data registration period comprising the continuous recording of muscle sympathetic nerve activity (MSNA) and respiration and of various other measurements at Visit 1, placebo and 50 μg of salmeterol via Diskus™ inhaler will be administered in a sequential design. Following Visit 1, the subjects will be treated with salmeterol 50 μg twice daily via Diskus inhaler for 4 weeks. At the Final Visit (Visit 2) the data registration period of Visit 1 will be repeated with the only difference that no placebo will be administered. Further endpoints, besides the evaluation of MSNA, include heart rate variability (HRV), spontaneous baroreflex sensitivity and lung function parameters. Study enrolment will be stopped when valid MSNA data on the immediate effect of inhalation (manoeuvres at Visit 1) are available for 24 subjects.
Interventions
DRUGSalmeterol
At visit 1 the sympathetic activity will be registered using microneurographic recordings of efferent muscle sympathetic nerve activity (MSNA) in the peroneal nerve and respiration over 2 hours, after 20 minutes of recording, 1 dose of placebo will be administered and after a further recording period of 45 minutes a dose of salmeterol 50 µg will be administered which will be followed by a further period of data registration. At visit 2 following 4 weeks of inhaled treatment with salmeterol the same procedures will be performed but a placebo inhalation will not be performed.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
41 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* COPD of GOLD Class II or III with a post-bronchodilator spirometry forced expiratory volume in one second (FEV1) \<60% predicted and FEV1/vital capacity (VC) \<70% in accordance with the GOLD executive summary * Subject is ambulatory (outpatient) * Subject is therapy-naive (defined as not receiving any previous regular COPD therapy) * Subjects with a current or prior history of ≥10 pack-years of cigarette smoking at Screening Visit. Previous smokers are defined as those who have stopped smoking for at least 1 month prior to Visit 1 * Willing to participate in the study, must be able to inhale study medication
Exclusion criteria
* Women who are pregnant or lactating * Subjects not willing or unable to sign the informed consent before study start * diagnosis of asthma * α-1 antitrypsin deficiency * active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases * Subjects with lung volume reduction surgery within the 12 months prior to Screening * Subjects who have been hospitalized due to poorly controlled COPD within 6 weeks prior to the Screening Visit * Subjects with poorly controlled COPD, defined as the occurrence of an exacerbation managed with systemic corticosteroids or antibiotics prescribed by a physician 6 weeks prior to the Screening Visit * Frequent exacerbations necessitating the therapy with inhaled glucocorticosteroids according to the GOLD guideline * COPD with nasal intermittent positive pressure ventilation (NIPPV) * Treatment with drugs having direct sympathomimetic activity (e.g. theophylline, moxonidine, clonidine), Oral medication with beta2-sympathomimetics * Inhaled therapy with anti-cholinergics, sodium cromoglycate or nedocromil sodium * Treatment with systemic, oral or parenteral (intra-articular) corticosteroids * Treatment with strong cytochrome P450 3A4 inhibitors * Treatment with any other investigational drug * Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day * Subjects who are medically unable to withhold their short-acting beta-agonist (SABA) for the 6-hour period required prior to spirometry testing at each study visit * Subjects with clinically significant sleep apnoea that is uncontrolled * Unstable angina pectoris or signs and history of left heart failure with a left ventricular ejection fraction \<40% * Arterial hypertension necessitating treatment with \>1 antihypertensive drug * Clinically evident polyneuropathy * Diabetes mellitus necessitating any pharmacological therapy * Severe concomitant disease (likely to reduce life expectancy to less than 3 years) * Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant neurological, psychiatric, renal, hepatic, immunological, endocrine or haematological abnormality that is uncontrolled
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Muscle Sympathetic Nerve Activity (MSNA) at 2 Hours (Week 0) | Baseline and 2 hours (Week 0) | Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. The change in MSNA (bursts per 100 heart beats \[bursts/100 heart beats\]) was calculated as the difference in MSNA change from Baseline to after the inhalation of salmeterol (2 hours, Week 0, Visit 1) minus the MSNA change from Baseline to after the inhalation of placebo (1 hour, Week 0, Visit 1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at 2 Hours (Week 0) | Baseline and 2 hours (Week 0) | Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. The change in MSNA (bursts per minute \[bursts/minute\]) was calculated as the difference in MSNA change from Baseline to after the inhalation of salmeterol (2 hours, Week 0, Visit 1) minus the MSNA change from Baseline to after the inhalation of placebo (1 hour, Week 0, Visit 1). |
| Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at Week 4 | Baseline and Week 4 | Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. Change in MSNA is expressed in terms of bursts per minute (bursts/minute). Change from Baseline was calculated as the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Standard Deviation of NN Intervals (SDNN) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Baseline, 2 hours (Week 0), and Week 4 | Heart rate variability (HRV) refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. SDNN reflects all the cyclic components responsible for variability in the period of recording; therefore, it represents total variability. Change in HRV (SDNN) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Standard Deviation of NN Intervals (SDNN) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. SDNN reflects all the cyclic components responsible for variability in the period of recording; therefore, it represents total variability. Change in HRV (SDNN) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Square Root of the Mean Squared Difference of Successive NNs (RMSSD) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. Compared with SDNN, RMSSD is a short-term variation of heart rate. Change in HRV (RMSSD) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Square Root of the Mean Squared Difference of Successive NNs (RMSSD) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. Compared with SDNN, RMSSD is a short-term variation of heart rate. Change in HRV (RMSSD) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Absolute Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (absolute LF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms\^2). Change from Baseline were calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Absolute Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (N-N) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: The LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (absolute LF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms2). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation), respectively. |
| Change From Baseline in Heart Rate Variability (HRV): Absolute High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (absolute HF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms\^2). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Absolute High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (absolute HF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms\^2). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Normalized Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (normalized LF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of LF power component in proportion to the total power minus the very LF (VLF) component (LF/(Total Power-VLF)\*100). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Normalized Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: The LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (normalized LF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of LF power component in proportion to the total power minus the very LF (VLF) component (LF/(Total Power-VLF)\*100). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Normalized High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (normalized HF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of HF power component in proportion to the total power minus the very LF (VLF) component (HF/(Total Power-VLF)\*100). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Normalized High Frequency Power (HF) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Baseline, 2 hours (Week 0), and Week 4 | HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (normalized HF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of HF power component in proportion to the total power minus the very LF (VLF) component (HF/(Total Power-VLF)\*100). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Heart Rate at 2 Hours (Week 0) and at Week 4 (ITT Population) | Baseline, 2 hours (Week 0), and Week 4 | Heart rate refers to the speed of the heartbeat, specifically the number of heartbeats per unit of time. Change in HRV (heart rate) after salmeterol inhalation is expressed in terms of the heart rate (beats) per minute (heart rate/min). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation). |
| Change From Baseline in Heart Rate Variability (HRV): Heart Rate at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Baseline, 2 hours (Week 0), and Week 4 | Heart rate refers to the speed of the heartbeat, specifically the number of heartbeats per unit of time. Change in HRV (heart rate) after salmeterol inhalation is expressed in terms of the heart rate (beats) per minute (heart rate/min). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation). |
| Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/100 Heart Beats) at Week 4 | Baseline and Week 4 | Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. Change in MSNA is expressed in terms of bursts per 100 heart beats (bursts/100 heart beats). Change from Baseline was calculated as the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Spontaneous Baroreflex Sensitivity (BRS) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Baseline, 2 hours (Week 0), and Week 4 | BRS is an important characteristic of baroreflex control and is often noninvasively assessed by relating heart rate (HR) fluctuations to blood pressure (BP) fluctuations. Change in BRS after salmeterol inhalation is expressed in terms of milliseconds per millimeters of mercury (ms/mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation). |
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Baseline, 2 hours (Week 0), and Week 4 | Pulmonary function was measured by FEV1, defined as the volume of air that which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change in FEV1 after salmeterol inhalation is expressed in terms of liters (L). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Baseline, 2 hours (Week 0), and Week 4 | Pulmonary function was measured by FEV1, defined as the volume of air that which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change in FEV1 after salmeterol inhalation is expressed in terms of liters (L). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at 2 Hours (Week 0) and at Week 4 | Baseline, 2 hours (Week 0), and Week 4 | Systolic and diastolic BP was manually measured. Change in BP after salmeterol inhalation is expressed in terms of millimeters of mercury (mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Respiratory Rate at 2 Hours (Week 0) and at Week 4 | Baseline, 2 hours (Week 0), and Week 4 | Respiratory rate is defined as the number of breaths taken within a set amount of time (typically within 60 seconds). Change in respiratory rate after salmeterol inhalation is expressed in terms of respiratory rate (breaths) per minute (min). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Tidal Volume at 2 Hours (Week 0) and at Week 4 | Baseline, 2 hours (Week 0), and Week 4 | Tidal volume is defined as the lung volume representing the normal volume of air displaced between normal inspiration and expiration when extra effort is not applied (normal value is approximately 500 milliliters or 7 milliliters per kilogram of body weight). Change in tidal volume after salmeterol inhalation is expressed in terms of milliliters (mL). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Respiratory Minute Volume at 2 Hours (Week 0) and at Week 4 | Baseline, 2 hours (Week 0), and Week 4 | Respiratory minute volume is defined as the volume of gas inhaled (inhaled minute volume) or exhaled (exhaled minute volume) from a person's lungs per minute. Change in respiratory minute volume after salmeterol inhalation is expressed in terms of milliliters per minute (mL/min). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Catecholamines (Plasma Norepinephrine) at 2 Hours (Week 0) and at Week 4 | Baseline, 2 hours (Week 0), and Week 4 | Catecholamines are important neurotransmitters in the central nervous system and play a crucial role in the autonomic regulation of many homeostatic functions. Change in catecholamines (plasma norepinephrine) after salmeterol inhalation is expressed in terms of nanogramms per liter (ng/L). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Catecholamines (Plasma Epinephrine) at 2 Hours (Week 0) and at Week 4 | Baseline, 2 hours (Week 0), and Week 4 | Catecholamines are important neurotransmitters in the central nervous system and play a crucial role in the autonomic regulation of many homeostatic functions. Change in catecholamines (plasma epinephrine) after salmeterol inhalation is expressed in terms of nanograms per milliliter (ng/mL). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Catecholamines (Brain Natriuretic Peptide [BNP]) at 2 Hours (Week 0) and at Week 4 | Baseline, 2 hours (Week 0), and Week 4 | Catecholamines are important neurotransmitters in the central nervous system and play a crucial role in the autonomic regulation of many homeostatic functions. Change in catecholamines (BNP) after salmeterol inhalation is expressed in terms of picograms per milliliter (pg/mL). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry (SpO2) at 2 Hours (Week 0) and at Week 4 | Baseline, 2 hours (Week 0), and Week 4 | Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen binds to hemoglobin in red blood cells when moving through the lungs. A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen. The percentage is called blood oxygen saturation, or SpO2. Change in SpO2 after salmeterol inhalation is expressed in terms of percent. Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Change From Baseline in Transcutaneous Carbon Dioxide (tCO2) at 2 Hours (Week 0) and at Week 4 | Baseline, 2 hours (Week 0), and Week 4 | Transcutaneous carbon dioxide monitoring is a noninvasive way of continuously measuring the tension of these gases in the skin. This methodology provides a continuous noninvasive estimation of the arterial CO2 value. Change in tCO2 after salmeterol inhalation is expressed in terms of millimeters of mercury (mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation). |
| Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | Baseline and Week 4 | FVC is defined as the volume of air that can be forcibly blown out from the lungs after a full inspiration. FRC is defined as the volume of air present in the lungs, specifically the parenchyma tissues, at the end of a passive expiration. TLC is defined as the maximum volume to which the lungs can be expanded with the greatest possible inspiratory effort; it is equal to VC plus the RV and is approximately 5800 milliliters. RV is defined as the amount of gas remaining in the lungs at the end of a maximal exhalation. All parameters describing lung function are expressed in terms of liters (L). Lung function (FVC, FRC \[body and helium\], TLC, and RV) was evaluated at Baseline (Week 0, \[Visit 1, before any inhalation\]) and at Week 4 (Visit 2, after salmeterol inhalation). |
| Number of Participants With Diastolic Dysfunction on Echocardiography at Baseline (Week 0) and at Week 4 | Baseline and Week 4 | Diastolic dysfunction refers to the decline in performance of one (usually the left ventricle) or both (left and right) ventricles during diastole. The number of participants with diastolic dysfunction on echocardiography was evaluated at Baseline (Week 0, \[Visit 1, before any inhalation\]) and at Week 4 (Visit 2, after salmeterol inhalation). |
| Arterial Stiffness at Baseline (Week 0) and at Week 4 | Baseline and Week 4 | Arterial stiffness occurs as a consequence of age and arteriosclerosis. Carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, is determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. PWV was evaluated in terms of meters per second (m/s). PWV after salmeterol inhalation at Baseline (Week 0, \[Visit 1, before any inhalation\]) and at Week 4 (Visit 2, after inhalation of salmeterol) was assessed. |
| Change From Baseline in Spontaneous Baroreflex Sensitivity (BRS) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Baseline, 2 hours (Week 0), and Week 4 | BRS is an important characteristic of baroreflex control and is often noninvasively assessed by relating heart rate (HR) fluctuations to blood pressure (BP) fluctuations. Change in BRS after salmeterol inhalation is expressed in terms of milliseconds per millimeters of mercury (ms/mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation). |
Countries
Germany
Participant flow
Pre-assignment details
At Visit 1, a complex data registration was performed during which placebo and 50 micrograms (µg) salmeterol via SEREVENT DISKUS inhaler was administered sequentially. Following Visit 1, participants were treated with salmeterol 50 µg twice daily (BID) via DISKUS inhaler for 4 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Salmeterol 50 µg BID Participants received salmeterol 50 micrograms (µg) via DISKUS inhaler twice daily (BID) over the course of 4 weeks. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Salmeterol 50 µg BID |
|---|---|
| Age, Continuous | 61.19 Years STANDARD_DEVIATION 8.41 |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
Primary
Change in Muscle Sympathetic Nerve Activity (MSNA) at 2 Hours (Week 0)
Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. The change in MSNA (bursts per 100 heart beats \[bursts/100 heart beats\]) was calculated as the difference in MSNA change from Baseline to after the inhalation of salmeterol (2 hours, Week 0, Visit 1) minus the MSNA change from Baseline to after the inhalation of placebo (1 hour, Week 0, Visit 1).
Time frame: Baseline and 2 hours (Week 0)
Population: ITT-MSNA Population: all participants who received at least one dose of study medication and who had a valid data registration period of the primary endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salmeterol 50 µg BID | Change in Muscle Sympathetic Nerve Activity (MSNA) at 2 Hours (Week 0) | -1.3 Bursts/100 heart beats | Standard Deviation 8.13 |
p-value: 0.5062paired t-Test, 2-sided
Secondary
Arterial Stiffness at Baseline (Week 0) and at Week 4
Arterial stiffness occurs as a consequence of age and arteriosclerosis. Carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, is determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. PWV was evaluated in terms of meters per second (m/s). PWV after salmeterol inhalation at Baseline (Week 0, \[Visit 1, before any inhalation\]) and at Week 4 (Visit 2, after inhalation of salmeterol) was assessed.
Time frame: Baseline and Week 4
Population: ITT Population. Only those participants available at the specified time points were assessed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Arterial Stiffness at Baseline (Week 0) and at Week 4 | PWV at Baseline, Week 0, n=30 | 9.2 m/s | Standard Deviation 2.1 |
| Salmeterol 50 µg BID | Arterial Stiffness at Baseline (Week 0) and at Week 4 | PWV at Week 4, n=29 | 8.8 m/s | Standard Deviation 2.2 |
Secondary
Change From Baseline in Catecholamines (Brain Natriuretic Peptide [BNP]) at 2 Hours (Week 0) and at Week 4
Catecholamines are important neurotransmitters in the central nervous system and play a crucial role in the autonomic regulation of many homeostatic functions. Change in catecholamines (BNP) after salmeterol inhalation is expressed in terms of picograms per milliliter (pg/mL). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Catecholamines (Brain Natriuretic Peptide [BNP]) at 2 Hours (Week 0) and at Week 4 | Change from Baseline to 2 hours, Week 0 | 2.4 pg/mL | Standard Deviation 7 |
| Salmeterol 50 µg BID | Change From Baseline in Catecholamines (Brain Natriuretic Peptide [BNP]) at 2 Hours (Week 0) and at Week 4 | Change from Baseline to Week 4 | -6.1 pg/mL | Standard Deviation 28.5 |
Secondary
Change From Baseline in Catecholamines (Plasma Epinephrine) at 2 Hours (Week 0) and at Week 4
Catecholamines are important neurotransmitters in the central nervous system and play a crucial role in the autonomic regulation of many homeostatic functions. Change in catecholamines (plasma epinephrine) after salmeterol inhalation is expressed in terms of nanograms per milliliter (ng/mL). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the specified time points were assessed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Catecholamines (Plasma Epinephrine) at 2 Hours (Week 0) and at Week 4 | Change from Baseline to 2 hours, Week 0, n=26 | 6.7 ng/mL | Standard Deviation 12.7 |
| Salmeterol 50 µg BID | Change From Baseline in Catecholamines (Plasma Epinephrine) at 2 Hours (Week 0) and at Week 4 | Change from Baseline to Week 4, n=29 | -0.3 ng/mL | Standard Deviation 10.4 |
Secondary
Change From Baseline in Catecholamines (Plasma Norepinephrine) at 2 Hours (Week 0) and at Week 4
Catecholamines are important neurotransmitters in the central nervous system and play a crucial role in the autonomic regulation of many homeostatic functions. Change in catecholamines (plasma norepinephrine) after salmeterol inhalation is expressed in terms of nanogramms per liter (ng/L). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the specified time points were assessed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Catecholamines (Plasma Norepinephrine) at 2 Hours (Week 0) and at Week 4 | Change from Baseline to 2 hours, Week 0, n=26 | -42.4 ng/L | Standard Deviation 103 |
| Salmeterol 50 µg BID | Change From Baseline in Catecholamines (Plasma Norepinephrine) at 2 Hours (Week 0) and at Week 4 | Change from Baseline to Week 4, n=29 | -5.7 ng/L | Standard Deviation 133 |
Secondary
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population)
Pulmonary function was measured by FEV1, defined as the volume of air that which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change in FEV1 after salmeterol inhalation is expressed in terms of liters (L). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT-MSNA Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to 2 hours, Week 0 | -0.05 L | Standard Deviation 0.26 |
| Salmeterol 50 µg BID | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to Week 4 | -0.08 L | Standard Deviation 0.21 |
Secondary
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at 2 Hours (Week 0) and at Week 4 (ITT Population)
Pulmonary function was measured by FEV1, defined as the volume of air that which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change in FEV1 after salmeterol inhalation is expressed in terms of liters (L). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to 2 hours, Week 0, n=32 | -0.04 L | Standard Deviation 0.23 |
| Salmeterol 50 µg BID | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to Week 4, n=31 | -0.04 L | Standard Deviation 0.21 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Absolute High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (absolute HF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms\^2). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT-MSNA Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Absolute High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to 2 hours, Week 0 | -372.1 ms^2 | Standard Deviation 1194.4 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Absolute High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to Week 4 | -840.2 ms^2 | Standard Deviation 1491.5 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Absolute High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (absolute HF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms\^2). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Absolute High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to 2 hours, Week 0, n=32 | -457.9 ms^2 | Standard Deviation 1591.6 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Absolute High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to Week 4, n=31 | 817.5 ms^2 | Standard Deviation 8754.6 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Absolute Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population)
HRV refers to the complex beat-to-beat (N-N) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: The LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (absolute LF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms2). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation), respectively.
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT-MSNA Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Absolute Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to 2 hours, Week 0 | 220.7 ms^2 | Standard Deviation 1038.2 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Absolute Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to Week 4 | -248.1 ms^2 | Standard Deviation 755.2 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Absolute Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (absolute LF) after salmeterol inhalation is expressed in terms of milliseconds squared (ms\^2). Change from Baseline were calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Absolute Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to 2 hours, Week 0, n=32 | -123.8 ms^2 | Standard Deviation 1588.4 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Absolute Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to Week 4, n=31 | -390.1 ms^2 | Standard Deviation 1463.3 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Heart Rate at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population)
Heart rate refers to the speed of the heartbeat, specifically the number of heartbeats per unit of time. Change in HRV (heart rate) after salmeterol inhalation is expressed in terms of the heart rate (beats) per minute (heart rate/min). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT-MSNA Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Heart Rate at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to 2 hours, Week 0 | 4.4 beats per minute (bpm) | Standard Deviation 4.7 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Heart Rate at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to Week 4 | 4.9 beats per minute (bpm) | Standard Deviation 4.8 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Heart Rate at 2 Hours (Week 0) and at Week 4 (ITT Population)
Heart rate refers to the speed of the heartbeat, specifically the number of heartbeats per unit of time. Change in HRV (heart rate) after salmeterol inhalation is expressed in terms of the heart rate (beats) per minute (heart rate/min). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Heart Rate at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to 2 hours, Week 0, n=32 | 3.7 beats per minute (bpm) | Standard Deviation 4.2 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Heart Rate at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to Week 4, n=31 | 3.9 beats per minute (bpm) | Standard Deviation 4.3 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Normalized High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (normalized HF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of HF power component in proportion to the total power minus the very LF (VLF) component (HF/(Total Power-VLF)\*100). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Normalized High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to 2 hours, Week 0, n=32 | -8.4 percent change | Standard Deviation 14.5 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Normalized High Frequency (HF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to Week 4, n=31 | -2.5 percent change | Standard Deviation 23.3 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Normalized High Frequency Power (HF) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the HF component of the HRV spectrum reflects parasympathetic activity. Change in HRV (normalized HF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of HF power component in proportion to the total power minus the very LF (VLF) component (HF/(Total Power-VLF)\*100). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT-MSNA Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Normalized High Frequency Power (HF) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to 2 hours, Week 0 | -10.8 percent change | Standard Deviation 14.6 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Normalized High Frequency Power (HF) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to Week 4 | -11.6 percent change | Standard Deviation 19 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Normalized Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: The LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (normalized LF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of LF power component in proportion to the total power minus the very LF (VLF) component (LF/(Total Power-VLF)\*100). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT-MSNA Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Normalized Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to 2 hours, Week 0 | 10.8 percent change | Standard Deviation 14.6 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Normalized Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to Week 4 | 11.6 percent change | Standard Deviation 19 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Normalized Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. HRV frequencies can be analyzed with frequency domain methods: the LF component of the HRV spectrum reflects sympathetic activity. Change in HRV (normalized LF) after salmeterol inhalation is expressed in terms of normalized units that represent the relative value of LF power component in proportion to the total power minus the very LF (VLF) component (LF/(Total Power-VLF)\*100). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Normalized Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to 2 hours, Week 0, n=32 | 8.4 percent change | Standard Deviation 14.5 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Normalized Low Frequency (LF) Power at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to Week 4, n=31 | 2.5 percent change | Standard Deviation 23.3 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Square Root of the Mean Squared Difference of Successive NNs (RMSSD) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. Compared with SDNN, RMSSD is a short-term variation of heart rate. Change in HRV (RMSSD) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT-MSNA Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Square Root of the Mean Squared Difference of Successive NNs (RMSSD) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to 2 hours, Week 0 | -10.6 ms | Standard Deviation 26.4 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Square Root of the Mean Squared Difference of Successive NNs (RMSSD) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to Week 4 | -32.5 ms | Standard Deviation 47.4 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Square Root of the Mean Squared Difference of Successive NNs (RMSSD) at 2 Hours (Week 0) and at Week 4 (ITT Population)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. Compared with SDNN, RMSSD is a short-term variation of heart rate. Change in HRV (RMSSD) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Square Root of the Mean Squared Difference of Successive NNs (RMSSD) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to 2 hours, Week 0, n=32 | -11.5 ms | Standard Deviation 36.3 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Square Root of the Mean Squared Difference of Successive NNs (RMSSD) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to Week 4, n=31 | -5.2 ms | Standard Deviation 96.1 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Standard Deviation of NN Intervals (SDNN) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population)
HRV refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. SDNN reflects all the cyclic components responsible for variability in the period of recording; therefore, it represents total variability. Change in HRV (SDNN) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT-MSNA Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Standard Deviation of NN Intervals (SDNN) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to 2 hours, Week 0 | 1.2 ms | Standard Deviation 22.5 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Standard Deviation of NN Intervals (SDNN) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to Week 4 | -12.1 ms | Standard Deviation 29.5 |
Secondary
Change From Baseline in Heart Rate Variability (HRV): Standard Deviation of NN Intervals (SDNN) at 2 Hours (Week 0) and at Week 4 (ITT Population)
Heart rate variability (HRV) refers to the complex beat-to-beat (NN) variation in heart rate produced by the interplay of sympathetic and parasympathetic neural activity at the sinus node of the heart. SDNN reflects all the cyclic components responsible for variability in the period of recording; therefore, it represents total variability. Change in HRV (SDNN) after salmeterol inhalation is expressed in terms of milliseconds (ms). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Standard Deviation of NN Intervals (SDNN) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to 2 hours, Week 0, n=32 | -1.7 ms | Standard Deviation 26.4 |
| Salmeterol 50 µg BID | Change From Baseline in Heart Rate Variability (HRV): Standard Deviation of NN Intervals (SDNN) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to Week 4, n=31 | 0.1 ms | Standard Deviation 53.9 |
Secondary
Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/100 Heart Beats) at Week 4
Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. Change in MSNA is expressed in terms of bursts per 100 heart beats (bursts/100 heart beats). Change from Baseline was calculated as the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline and Week 4
Population: ITT-MSNA Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/100 Heart Beats) at Week 4 | -3.1 Bursts/100 heart beats | Standard Deviation 11.58 |
Secondary
Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at 2 Hours (Week 0)
Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. The change in MSNA (bursts per minute \[bursts/minute\]) was calculated as the difference in MSNA change from Baseline to after the inhalation of salmeterol (2 hours, Week 0, Visit 1) minus the MSNA change from Baseline to after the inhalation of placebo (1 hour, Week 0, Visit 1).
Time frame: Baseline and 2 hours (Week 0)
Population: ITT-MSNA Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at 2 Hours (Week 0) | 0.3 Bursts/minute | Standard Deviation 5.6 |
Secondary
Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at Week 4
Human MSNA is composed of vasoconstrictor impulses grouped in pulse synchronous bursts that usually occur in sequences, preferentially during transient reductions of blood pressure. Sympathetic activity was measured using microneurographic recordings of efferent in the peroneal nerve. MSNA reflects sympathetic discharge to the vascular bed of the skeletal muscle. Change in MSNA is expressed in terms of bursts per minute (bursts/minute). Change from Baseline was calculated as the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline and Week 4
Population: ITT-MSNA Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in MSNA (Evaluated by Microneurography as Bursts/Minute) at Week 4 | 0.5 Bursts/minute | Standard Deviation 7.58 |
Secondary
Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry (SpO2) at 2 Hours (Week 0) and at Week 4
Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen binds to hemoglobin in red blood cells when moving through the lungs. A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen. The percentage is called blood oxygen saturation, or SpO2. Change in SpO2 after salmeterol inhalation is expressed in terms of percent. Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: Safety Population: all participants included in the study who received at least one dose of study medication. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry (SpO2) at 2 Hours (Week 0) and at Week 4 | Change from Baseline to 2 hours, Week 0, n=32 | -0.2 percent | Standard Deviation 1.1 |
| Salmeterol 50 µg BID | Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry (SpO2) at 2 Hours (Week 0) and at Week 4 | Change from Baseline to Week 4, n=31 | -0.5 percent | Standard Deviation 2 |
Secondary
Change From Baseline in Respiratory Minute Volume at 2 Hours (Week 0) and at Week 4
Respiratory minute volume is defined as the volume of gas inhaled (inhaled minute volume) or exhaled (exhaled minute volume) from a person's lungs per minute. Change in respiratory minute volume after salmeterol inhalation is expressed in terms of milliliters per minute (mL/min). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the specified time points were assessed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Respiratory Minute Volume at 2 Hours (Week 0) and at Week 4 | Change from Baseline to 2 hours, Week 0, n=30 | 572.0 mL/min | Standard Deviation 1529.7 |
| Salmeterol 50 µg BID | Change From Baseline in Respiratory Minute Volume at 2 Hours (Week 0) and at Week 4 | Change from Baseline to Week 4, n=24 | 671.4 mL/min | Standard Deviation 2963.3 |
Secondary
Change From Baseline in Respiratory Rate at 2 Hours (Week 0) and at Week 4
Respiratory rate is defined as the number of breaths taken within a set amount of time (typically within 60 seconds). Change in respiratory rate after salmeterol inhalation is expressed in terms of respiratory rate (breaths) per minute (min). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Respiratory Rate at 2 Hours (Week 0) and at Week 4 | Change from Baseline to 2 hours, Week 0, n=32 | -0.5 breaths per minute | Standard Deviation 1.6 |
| Salmeterol 50 µg BID | Change From Baseline in Respiratory Rate at 2 Hours (Week 0) and at Week 4 | Change from Baseline to Week 4, n=31 | -0.1 breaths per minute | Standard Deviation 2.6 |
Secondary
Change From Baseline in Spontaneous Baroreflex Sensitivity (BRS) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population)
BRS is an important characteristic of baroreflex control and is often noninvasively assessed by relating heart rate (HR) fluctuations to blood pressure (BP) fluctuations. Change in BRS after salmeterol inhalation is expressed in terms of milliseconds per millimeters of mercury (ms/mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT-MSNA Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Spontaneous Baroreflex Sensitivity (BRS) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to 2 hours, Week 0 | 0.28 ms/mmHg | Standard Deviation 2.2 |
| Salmeterol 50 µg BID | Change From Baseline in Spontaneous Baroreflex Sensitivity (BRS) at 2 Hours (Week 0) and at Week 4 (ITT-MSNA Population) | Change from Baseline to Week 4 | 0.44 ms/mmHg | Standard Deviation 3.2 |
Secondary
Change From Baseline in Spontaneous Baroreflex Sensitivity (BRS) at 2 Hours (Week 0) and at Week 4 (ITT Population)
BRS is an important characteristic of baroreflex control and is often noninvasively assessed by relating heart rate (HR) fluctuations to blood pressure (BP) fluctuations. Change in BRS after salmeterol inhalation is expressed in terms of milliseconds per millimeters of mercury (ms/mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0 before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the specified time points were assessed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Spontaneous Baroreflex Sensitivity (BRS) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to 2 hours, Week 0, n=31 | 0.1 ms/mmHg | Standard Deviation 1.9 |
| Salmeterol 50 µg BID | Change From Baseline in Spontaneous Baroreflex Sensitivity (BRS) at 2 Hours (Week 0) and at Week 4 (ITT Population) | Change from Baseline to Week 4, n=29 | 0.2 ms/mmHg | Standard Deviation 2.6 |
Secondary
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at 2 Hours (Week 0) and at Week 4
Systolic and diastolic BP was manually measured. Change in BP after salmeterol inhalation is expressed in terms of millimeters of mercury (mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at 2 Hours (Week 0) and at Week 4 | Systolic: Change from Baseline to 2 hours, Week 0 | 3.6 mmHg | Standard Deviation 12.3 |
| Salmeterol 50 µg BID | Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at 2 Hours (Week 0) and at Week 4 | Systolic: Change from Baseline to Week 4 | 3.7 mmHg | Standard Deviation 15.7 |
| Salmeterol 50 µg BID | Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at 2 Hours (Week 0) and at Week 4 | Diastolic: Change from Baseline to 2 hours, Week 0 | 1.9 mmHg | Standard Deviation 6.7 |
| Salmeterol 50 µg BID | Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at 2 Hours (Week 0) and at Week 4 | Diastolic: Change from Baseline to Week 4 | 0.7 mmHg | Standard Deviation 6.8 |
Secondary
Change From Baseline in Tidal Volume at 2 Hours (Week 0) and at Week 4
Tidal volume is defined as the lung volume representing the normal volume of air displaced between normal inspiration and expiration when extra effort is not applied (normal value is approximately 500 milliliters or 7 milliliters per kilogram of body weight). Change in tidal volume after salmeterol inhalation is expressed in terms of milliliters (mL). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: ITT Population. Only those participants available at the specified time points were assessed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Tidal Volume at 2 Hours (Week 0) and at Week 4 | Change from Baseline to 2 hours, Week 0, n=30 | 60.4 mL | Standard Deviation 118 |
| Salmeterol 50 µg BID | Change From Baseline in Tidal Volume at 2 Hours (Week 0) and at Week 4 | Change from Baseline to Week 4, n=24 | 55.6 mL | Standard Deviation 183.7 |
Secondary
Change From Baseline in Transcutaneous Carbon Dioxide (tCO2) at 2 Hours (Week 0) and at Week 4
Transcutaneous carbon dioxide monitoring is a noninvasive way of continuously measuring the tension of these gases in the skin. This methodology provides a continuous noninvasive estimation of the arterial CO2 value. Change in tCO2 after salmeterol inhalation is expressed in terms of millimeters of mercury (mmHg). Change from Baseline was calculated as the value at 2 hours (Week 0 \[Visit 1, after salmeterol inhalation\]) and the value at Week 4 (Visit 2, after salmeterol inhalation) minus the value at Baseline (Week 0, before any inhalation).
Time frame: Baseline, 2 hours (Week 0), and Week 4
Population: Safety Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Change From Baseline in Transcutaneous Carbon Dioxide (tCO2) at 2 Hours (Week 0) and at Week 4 | Change from Baseline to 2 hours, Week 0, n=32 | -0.94 mmHg | Standard Deviation 2.19 |
| Salmeterol 50 µg BID | Change From Baseline in Transcutaneous Carbon Dioxide (tCO2) at 2 Hours (Week 0) and at Week 4 | Change from Baseline to Week 4, n=31 | -0.82 mmHg | Standard Deviation 4.17 |
Secondary
Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4
FVC is defined as the volume of air that can be forcibly blown out from the lungs after a full inspiration. FRC is defined as the volume of air present in the lungs, specifically the parenchyma tissues, at the end of a passive expiration. TLC is defined as the maximum volume to which the lungs can be expanded with the greatest possible inspiratory effort; it is equal to VC plus the RV and is approximately 5800 milliliters. RV is defined as the amount of gas remaining in the lungs at the end of a maximal exhalation. All parameters describing lung function are expressed in terms of liters (L). Lung function (FVC, FRC \[body and helium\], TLC, and RV) was evaluated at Baseline (Week 0, \[Visit 1, before any inhalation\]) and at Week 4 (Visit 2, after salmeterol inhalation).
Time frame: Baseline and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Salmeterol 50 µg BID | Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | FVC at Baseline, Week 0, n=32 | 2.60 L | Standard Deviation 0.7 |
| Salmeterol 50 µg BID | Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | FVC at Week 4, n=31 | 2.64 L | Standard Deviation 0.7 |
| Salmeterol 50 µg BID | Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | FRC (body) at Baseline, Week 0, n=32 | 4.65 L | Standard Deviation 1.3 |
| Salmeterol 50 µg BID | Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | FRC (body) at Week 4, n=27 | 3.67 L | Standard Deviation 1.8 |
| Salmeterol 50 µg BID | Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | FRC (helium) at Baseline, Week 0, n=24 | 3.64 L | Standard Deviation 1 |
| Salmeterol 50 µg BID | Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | FRC (helium) at Week 4, n=24 | 3.38 L | Standard Deviation 0.8 |
| Salmeterol 50 µg BID | Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | TLC at Baseline, Week 0, n=32 | 6.61 L | Standard Deviation 1.4 |
| Salmeterol 50 µg BID | Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | TLC at Week 4, n=27 | 5.67 L | Standard Deviation 1.8 |
| Salmeterol 50 µg BID | Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | RV at Baseline, Week 0, n=32 | 3.90 L | Standard Deviation 1.3 |
| Salmeterol 50 µg BID | Lung Function (Forced Vital Capacity [FVC], Functional Residual Capacity [FRC; Body and Helium], Total Lung Capacity [TLC], and Residual Volume [RV]) at Baseline (Week 0) and at Week 4 | RV at Week 4, n=27 | 2.90 L | Standard Deviation 1.8 |
Secondary
Number of Participants With Diastolic Dysfunction on Echocardiography at Baseline (Week 0) and at Week 4
Diastolic dysfunction refers to the decline in performance of one (usually the left ventricle) or both (left and right) ventricles during diastole. The number of participants with diastolic dysfunction on echocardiography was evaluated at Baseline (Week 0, \[Visit 1, before any inhalation\]) and at Week 4 (Visit 2, after salmeterol inhalation).
Time frame: Baseline and Week 4
Population: ITT Population. Only those participants available at the indicated time points were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Salmeterol 50 µg BID | Number of Participants With Diastolic Dysfunction on Echocardiography at Baseline (Week 0) and at Week 4 | Baseline: Diastolic dysfunction: Yes, n=32 | 3 participants |
| Salmeterol 50 µg BID | Number of Participants With Diastolic Dysfunction on Echocardiography at Baseline (Week 0) and at Week 4 | Baseline: Diastolic dysfunction: No, n=32 | 29 participants |
| Salmeterol 50 µg BID | Number of Participants With Diastolic Dysfunction on Echocardiography at Baseline (Week 0) and at Week 4 | Week 4: Diastolic dysfunction: Yes, n=31 | 5 participants |
| Salmeterol 50 µg BID | Number of Participants With Diastolic Dysfunction on Echocardiography at Baseline (Week 0) and at Week 4 | Week 4: Diastolic dysfunction: No, n=31 | 26 participants |