Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Chronic Obstructive Pulmonary Disease (COPD), Magnesium stearate, GSK573719
Brief summary
The study drug which is an inhaled bronchodilator (lung airway relaxant)has been given to both healthy volunteers and to COPD patients before. This study will assess a new formulation of GSK573719. Many drugs are known to deteriorate over time. To make the study medicine less likely to deteriorate in its container, it is mixed with an inactive substance that helps to to maintain the quality of the study medicine. Previous studies have looked at GSK573719 with another inactive substance called Cellobiose Octaacetate (COA). This study will be looking at a new formulation of GSK573719 using Magnesium Stearate (MgSt) as the inactive substance. MgSt itself is not a medicine but is approved as a food ingredient and has also has been approved to be used in a number of marketed medical inhalers. The purpose of this study is to assess the safety and tolerability of compound GSK573719 with Magnesium Stearate for once-daily treatment of COPD(Chronic Obstructive Pulmonary Disease). This drug will be given to 2 groups of 12 people for 7 days. Group 1 will receive 250mcg or placebo and group 2 will receive 1000mcg or placebo. Group 2 will not be dosed until at least 6 people have completed dosing in group 1 without any significant safety concerns. The following safety measures will be assessed including: ECGs, heart rate, blood pressure, blood samples for safety labs, lung function and 24 hour monitoring of the heart. We will also take blood and urine samples to measure medication levels in the body. GlaxoSmithKline will be funding the research and it will be recruiting at Synexus in 7 of their centres in the UK.
Interventions
DRUGGSK573719
7 day repeat dose
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female between 40 and 75 years of age * A female subject is eligible to participate if she is of: * Non childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy, bilateral salpingectomy or bilateral oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL and estradiol \< 40 pg/ml (\<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. * Male subjects must agree to use one of the listed contraception methods. This criterion must be followed from the time of the first dose of study medication until 90 days post-last dose. * Subject diagnosed with COPD, as defined by the GOLD guidelines. * BMI within the range 18 - 34 kg/m2 (inclusive). * Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (Pack years = (cigarettes per day smoked/20) x number of years smoked)). * Average QTcB or QTcF ≤ 450 msec taken from triplicate assessments at screening; or QTc ≤ 480 msec in subjects with Bundle Branch Block. * Subject has a post-bronchodilator (400 μg salbutamol) FEV1 of ≥ 35% to ≤ 80% of predicted normal. * Subject has FEV1/FVC \< 0.7 post-bronchodilator (400 μg salbutamol). * Subjects have a 24hour holter recording that is within normal limits for the individual and does not demonstrate any clinically important abnormality that, in the opinion of the investigator, would make the subject unsuitable for participation in the study. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Subject is available to complete all study measurements and procedures.
Exclusion criteria
* Subjects who have a past or present disease, which as judged by the Investigator, may affect subject safety or influence the outcome of the study. * The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine and opiates. The detection of drugs taken for a legitimate medical purpose would not necessarily be an exclusion to study participation. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study. * Female subject has a positive pregnancy test. * A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. * A positive test for HIV antibody (if tested, according to local SOP's). * History of high alcohol consumption within 1 month of the study defined as: * an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine. * The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Exposure to more than four new chemical entities within 12 months prior to the first dosing day. * History of sensitivity to any of the study medications, or components thereof (including allergy to milk protein/lactose) or a history of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation. * Subject has donated a unit (400 mL) of blood within 60 days of screening or, intends to donate during the study. * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. * Unwillingness or inability to follow the procedures outlined in the protocol. * The subject is unable to use the novel dry powder inhaler correctly. * The subject requires treatment for prostate hypertrophy. * The subject has a history of narrow angle glaucoma. Respiratory criteria * Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the Investigator, compromise the safety of the subject or affect the interpretation of the results. * Subject has poorly controlled COPD, defined as the occurrence of any of the following: * Either: acute worsening of COPD that is managed by the subject at home requiring treatment with corticosteroids in the 2 weeks prior to the screening visit. * Or: more than two exacerbations in the previous 4 months prior to the screening visit that required a course of oral corticosteroids or, for which the subject was hospitalised. * Subject has had a respiratory tract infection in the 2 weeks prior to first dose. Cardiovascular criteria * Current congestive heart failure (greater than NYHA II) and myocardial infarction (within 9 months of the screening date). * A history of clinically significant arrhythmia or clinically important 24 h Holter findings that, in the opinion of the Investigator, would cause a safety concern for entry into the study. * A mean QTc(B) value at screening \>450msec, or an ECG that is not suitable for QT measurements (e.g. LBBB or poorly defined termination of the T wave). * Third degree heart block or pacemaker. * Risk factors for torsades des pointes (heart failure NYHA II-IV, familial long QT syndrome). * Elevated resting blood pressure or a mean blood pressure equal to or higher than 150/90 mmHg at screening. A history of and treatment for hypertension is acceptable provided control has been achieved for \> 2 months prior to screening. * A mean heart rate outside the range 50-100 bpm at screening. Concurrent medication criteria * Subject requires treatment with nebulised beta-2 agonist or nebulised anticholinergics. * Subject has received oral or parenteral corticosteroids within 2 weeks of screening. * Subject is unable to abstain from long-acting bronchodilators from 48 hours prior to the screening and treatment periods (i.e. the last assessment in the dosing period). (Note, subjects may resume use of their usual medication in between screening and the treatment period if the restrictions in Section 9 Concomitant Medications and Non-Drug Therapies are followed and provided the long acting bronchodilator component is stopped again 48h or more prior to dosing). * Subject is receiving co-medication with drugs which are commonly recognised to prolong the QTc interval (e.g. quinolones, amiodorane, disopyramide, quinidine, sotalol, chlorpromazine, haloperidol, ketoconazole, terfenadine, cisapride and terodiline). * Subject requires regular treatment with oral corticosteroids (prednisolone or equivalent). * Subject is receiving treatment with beta-blockers, except eye drops. * Subject is receiving treatment with long-term or short-term oxygen therapy, NIPPV or requires nocturnal positive pressure for sleep apnea.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7 | Day 1 and Day 7 | Blood samples were collected for the measurement of MCV pre-dose on Day 1 and Day 7. |
| Total Number of Salbutamol Doses Taken Over the 7 -Day Study Period | Day 1 to Day 7 | The total number of salbutamol doses taken per day was recorded by the participants in their dairy card over the entire 7-day treatment period. Diaries were reviewed by the Investigator when participants were admitted to the unit on Day 1, Day 7, and Day 8. Salbutamol was given as rescue medication, defined as a quick-relief or fast-acting medication that is given in addition to the investigational drug or placebo that can alleviate symptoms due to disease or lack of efficacy of the study treatment. |
| Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Day 1 and Day 7 | Blood samples were collected for the measurement of albumin, total protein, hemoglobin, and MCHC values pre-dose on Day 1 and Day 7. |
| Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | Day 1 and Day 7 | Blood samples were collected for the measurement of ALP, ALT, AST, and GGT Pre-dose on Day 1 and Day 7. |
| Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Day 1 and Day 7 | Blood samples were collected for the measurement of direct bilirubin, total bilirubin, and creatinine at pre-dose on Day 1 and Day 7. |
| Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Day 1 and Day 7 | Blood samples were collected for the measurement of calcium, glucose, potassium, sodium, and urea/BUN pre-dose on Day 1 and Day 7. |
| Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Day 1 and Day 7 | Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC), platelets, and white blood cell (WBC) count pre-dose on Day 1 and Day 7. |
| Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7 | Day 1 and Day 7 | Blood samples were collected for the measurement of MCH pre-dose on Day 1 and Day 7. |
| Mean Heart Rate (HR) on Days 1 and 7 | Day 1 (pre-dose and 15 minutes [min], 45 min, 1.5 hours [hr], 4 hr, and 8 hr post-dose) and Day 7 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr post-dose) | HR was measured in a semi-recumbent position at approximately 45 degrees after the participant was kept at rest for at least 5 minutes. HR was obtained at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose (PD) on Day 1 and at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr PD on Day 7. |
| Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) | From start of treatment to study day 12 | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An on-treatment adverse event is defined as an event that occurred between the start of investigational product and follow-up contact. Refer to the general SAE/non-serious AE module for a complete list of AEs reported in the study. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. |
| Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | Day 1 (pre-dose and 15 minutes [min], 45 min, 1.5 hours [hr], 4 hr, and 8 hr post-dose) and Day 7 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr post-dose) | Blood pressure was measured in a semi-recumbent position at approximately 45 degrees after the participant was kept at rest for at least 5 minutes. SBP and DBP were obtained at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose (PD) on Day 1 and at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr PD on Day 7. |
| Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 1 and Day 7 | Maximum heart rate (Max HR) and weighted mean (WM) from 0-4 hour on Days 1 and 7 were derived. Max HR (0-4 h) is defined as the maximum heart rate attained within 0-4 h. The weighted mean HR (0-4 h) was derived by calculating the area under the curve, and then dividing the value by the relevant time interval. Each of the maximum and weighted mean (0-4h) endpoints for heart rate, was statistically analyzed using a mixed effects model. The terms treatment, baseline, day and any relevant interactions were considered in the model. Least squares means are adjusted for treatment, Baseline, day, treatment by Baseline and Baseline by day interaction, where Baseline is defined as the mean of the three pre-dose assessments. |
| Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose) and Day 7 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr) | The number of participants with normal (NL), abnormal not clinically significant (Abn NCS), and abnormal clinically significant (Abn CS) ECG findings, as well as those with unavailable results (NA) at pre-dose (PD1, PD2, PD3), and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose (PD) on Day 1 and at pre-dose (PD1, PD2, PD3), and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr post-dose on Day 7 are reported. The following are of potential clinical importance: absolute QTc interval \>450 milliseconds (msec); increase from Baseline QTc \>60 msec; PR interval \<110 and \>220 msec; QRS interval \<75 and \>110 msec. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee. |
| Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening and Day 7 | Twenty-four hour Holter ECG values were obtained at Screening and on Day 7. During the Screening procedure and study, standard Holter monitors were used (in order to exclude participants with underlying cardiac arrhythmogenicity). During the treatment periods, Holter monitors were only switched on immediately prior to dosing (up to 15 minutes pre-dose) so as to capture Holter ECG data from the 24 hour period following dosing. The following summary data were transcribed into the Case Report Form: Maximum and mean (0 to24 hour) heart rate; normal and aberrant beats and arrhythmias. Analysis of the Holter tapes was arranged by GlaxoSmithKline.The number of participants with normal (NL), abnormal not clinically significant (Abn NCS), and abnormal clinically significant (Abn CS) ECG findings, as well as those with unavailable results (NA) at Screening and Day 7, are reported. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee. |
| Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7 | Day 7 | Maximum heart rate (Max HR) and mean HR from 0-24 hour Holter monitoring on treatment Day 7 were derived. The analysis was adjusted for treatment and Baseline, where Baseline is defined as the corresponding summary measure (i.e., mean heart rate \[0-24 hours\] or maximum heart rate \[0-24 hours\]) from screening records. |
| Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Screening, Day 1, and Day 7 | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured at Screening, pre-dose, and 4 hours (hr) post-dose on Day 1 and Day 7. FEV1 tests were repeated until three technically acceptable measurements were made. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of UMEC on Day 1 and Day 7 | Day 1 and Day 7: pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose; 24 hr post-dose on Day 7 | Cmax is defined as the maximum observed concentration of UMEC and was measured on Day 1 and Day 7. Blood samples were collected pre-dose and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose on Day 1 and Day 7. Also, a 24 hr blood sample was collected on Day 7. |
| Tmax and Tlastof UMEC on Day 1 and Day 7 | Day 1 and Day 7: pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose; 24 hr post-dose on Day 7 | Tmax is defined as the time to reach the observed maximum concentration, and tlast is defined as the time of the last quantifiable concentration of UMEC; both were measured on Day 1 and Day 7. Blood samples were collected pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose on Day 1 and Day 7. Also, a 24 hr blood sample was collected on Day 7. |
| Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | From 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1; from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7 | Urinary recovery of unchanged drug (UMEC) within the first 8, 12, and 24 hours (Ae\[0-8\], Ae\[0-12\], and Ae\[0-24\], respectively) on Day 1 and within the first 4, 8, 12, and 24 hours (Ae\[0-4\], Ae\[0-8\], Ae\[0-12\], and Ae\[0-24\], respectively) on Day 7 was estimated. Urine samples were collected from 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1 and from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7. |
| Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | From 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1; from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7 | The fraction of the total dose excreted (Fe) in each interval was estimated as the urinary recovery of unchanged drug (Ae) per dose. Urine samples were collected from 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1 and from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7. |
| Renal Clearance of UMEC on Day 1 and Day 7 | From 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1; from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7 | Renal clearance was calculated as the urinary recovery of unchanged drug from time zero to time x (Ae\[0-x\])/area under concentration from time zero to time x (AUC\[0-x\]) for the longest period of time after dosing when both could be accurately determined (where x is either 8, 12, or 24). Urine samples were collected from 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1 and from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7. |
| Urine Half Life (t1/2) of UMEC on Day 7 | From 0-4 hours (hr), 4-8 hr, 8-12 hr, and 12-24 hr on Day 7 | Urine half life (t1/2) of UMEC on Day 7 was estimated. Urine samples were collected from 0-4 hours (hr), 4-8 hr, 8-12 hr, and 12-24 hr on Day 7. |
| Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | Day 1 and Day 7: pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose; 24 hr post-dose on Day 7 | Area under the concentration-time (AUC) curve from time zero (pre-dose) to 2 hours (AUC\[0-2\]), from time zero to 8 hours (AUC\[0-8\]), from time zero to the last time of a quantifiable concentration of UMEC (AUC\[0-t\]) on Day 1 and Day 7 were measured. AUC is a measure of systemic exposure. Blood samples were collected pre-dose and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose on Day 1 and Day 7. Also, a 24 hr blood sample was collected on Day 7. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants=par.; umeclidinium=UMEC. A total of 37 unique par. were enrolled in the study; however, 1 par. was randomized and dosed on two separate occasions and is counted as two separate par. on all outputs (thus, 38 par. started study treatment).
Pre-assignment details
Participants were assigned to one of two cohorts: UMEC 250 micrograms (μg) once daily (QD) or placebo (Cohort 1) and UMEC 1000 μg QD or placebo (Cohort 2) for 7 days. After reporting of Cohorts 1 and 2, it was found that par. in Cohort 2 received UMEC 250 μg in error. Cohort 3 was then recruited, in which par. received UMEC 1000 μg QD or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI). | 9 |
| Cohort 1 UMEC 250 µg Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI. | 10 |
| Cohort 2 UMEC 250 µg in Error Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error. | 10 |
| Cohort 3 UMEC 1000 µg Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI. | 9 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Cohort 1 UMEC 250 µg | Cohort 2 UMEC 250 µg in Error | Cohort 3 UMEC 1000 µg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 66.2 Years STANDARD_DEVIATION 4.47 | 63.3 Years STANDARD_DEVIATION 8.21 | 64.7 Years STANDARD_DEVIATION 6.31 | 64.2 Years STANDARD_DEVIATION 7.97 | 64.6 Years STANDARD_DEVIATION 6.72 |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 9 participants | 10 participants | 10 participants | 9 participants | 38 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 2 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 8 Participants | 5 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 9 | 2 / 10 | 8 / 10 | 5 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 | 0 / 10 | 0 / 9 |
Outcome results
Primary
Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7
Blood samples were collected for the measurement of albumin, total protein, hemoglobin, and MCHC values pre-dose on Day 1 and Day 7.
Time frame: Day 1 and Day 7
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Albumin, Day 1, n=9, 9, 10, 9 | 42.3 Grams per liter (G/L) | Standard Deviation 3.43 |
| Placebo | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Albumin, Day 7, n=8, 7, 9, 6 | 43.1 Grams per liter (G/L) | Standard Deviation 1.81 |
| Placebo | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Total protein, Day 1, n=9, 9, 10, 9 | 69.4 Grams per liter (G/L) | Standard Deviation 5.48 |
| Placebo | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Total protein, Day 7, n=8, 7, 9, 6 | 68.6 Grams per liter (G/L) | Standard Deviation 3.16 |
| Placebo | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Hemoglobin, Day 1, n=9, 9, 10, 9 | 152.2 Grams per liter (G/L) | Standard Deviation 8.6 |
| Placebo | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Hemoglobin, Day 7, n=9, 6, 9, 6 | 151.4 Grams per liter (G/L) | Standard Deviation 7.8 |
| Placebo | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | MCHC, Day 1, n=9, 9, 10, 9 | 340.0 Grams per liter (G/L) | Standard Deviation 6.1 |
| Placebo | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | MCHC, Day 7, n=9, 6, 9, 6 | 337.6 Grams per liter (G/L) | Standard Deviation 7.84 |
| Cohort 1 UMEC 250 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Hemoglobin, Day 7, n=9, 6, 9, 6 | 145.8 Grams per liter (G/L) | Standard Deviation 14.77 |
| Cohort 1 UMEC 250 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Hemoglobin, Day 1, n=9, 9, 10, 9 | 148.0 Grams per liter (G/L) | Standard Deviation 14.19 |
| Cohort 1 UMEC 250 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Albumin, Day 7, n=8, 7, 9, 6 | 44.0 Grams per liter (G/L) | Standard Deviation 1.15 |
| Cohort 1 UMEC 250 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | MCHC, Day 7, n=9, 6, 9, 6 | 340.7 Grams per liter (G/L) | Standard Deviation 5.2 |
| Cohort 1 UMEC 250 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | MCHC, Day 1, n=9, 9, 10, 9 | 338.7 Grams per liter (G/L) | Standard Deviation 5.39 |
| Cohort 1 UMEC 250 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Total protein, Day 7, n=8, 7, 9, 6 | 70.0 Grams per liter (G/L) | Standard Deviation 2.16 |
| Cohort 1 UMEC 250 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Total protein, Day 1, n=9, 9, 10, 9 | 70.0 Grams per liter (G/L) | Standard Deviation 3.24 |
| Cohort 1 UMEC 250 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Albumin, Day 1, n=9, 9, 10, 9 | 43.9 Grams per liter (G/L) | Standard Deviation 2.09 |
| Cohort 2 UMEC 250 µg in Error | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | MCHC, Day 1, n=9, 9, 10, 9 | 339.9 Grams per liter (G/L) | Standard Deviation 5.49 |
| Cohort 2 UMEC 250 µg in Error | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Total protein, Day 1, n=9, 9, 10, 9 | 69.9 Grams per liter (G/L) | Standard Deviation 3.7 |
| Cohort 2 UMEC 250 µg in Error | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Total protein, Day 7, n=8, 7, 9, 6 | 71.0 Grams per liter (G/L) | Standard Deviation 4.53 |
| Cohort 2 UMEC 250 µg in Error | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Hemoglobin, Day 1, n=9, 9, 10, 9 | 147.4 Grams per liter (G/L) | Standard Deviation 11.84 |
| Cohort 2 UMEC 250 µg in Error | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Hemoglobin, Day 7, n=9, 6, 9, 6 | 147.4 Grams per liter (G/L) | Standard Deviation 13.71 |
| Cohort 2 UMEC 250 µg in Error | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | MCHC, Day 7, n=9, 6, 9, 6 | 337.4 Grams per liter (G/L) | Standard Deviation 5.59 |
| Cohort 2 UMEC 250 µg in Error | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Albumin, Day 1, n=9, 9, 10, 9 | 43.7 Grams per liter (G/L) | Standard Deviation 2.16 |
| Cohort 2 UMEC 250 µg in Error | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Albumin, Day 7, n=8, 7, 9, 6 | 43.8 Grams per liter (G/L) | Standard Deviation 2.64 |
| Cohort 3 UMEC 1000 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Total protein, Day 1, n=9, 9, 10, 9 | 69.8 Grams per liter (G/L) | Standard Deviation 3.46 |
| Cohort 3 UMEC 1000 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Total protein, Day 7, n=8, 7, 9, 6 | 69.7 Grams per liter (G/L) | Standard Deviation 3.83 |
| Cohort 3 UMEC 1000 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Albumin, Day 7, n=8, 7, 9, 6 | 44.0 Grams per liter (G/L) | Standard Deviation 2.61 |
| Cohort 3 UMEC 1000 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Albumin, Day 1, n=9, 9, 10, 9 | 44.1 Grams per liter (G/L) | Standard Deviation 3.1 |
| Cohort 3 UMEC 1000 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Hemoglobin, Day 1, n=9, 9, 10, 9 | 145.4 Grams per liter (G/L) | Standard Deviation 16.18 |
| Cohort 3 UMEC 1000 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | MCHC, Day 7, n=9, 6, 9, 6 | 337.3 Grams per liter (G/L) | Standard Deviation 5.2 |
| Cohort 3 UMEC 1000 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | MCHC, Day 1, n=9, 9, 10, 9 | 337.2 Grams per liter (G/L) | Standard Deviation 3.63 |
| Cohort 3 UMEC 1000 µg | Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 | Hemoglobin, Day 7, n=9, 6, 9, 6 | 143.5 Grams per liter (G/L) | Standard Deviation 16.61 |
Primary
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7
Blood samples were collected for the measurement of ALP, ALT, AST, and GGT Pre-dose on Day 1 and Day 7.
Time frame: Day 1 and Day 7
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALP, Day 1, n=9, 9, 10, 9 | 74.0 International units per liter (IU/L) | Standard Deviation 20.2 |
| Placebo | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALP, Day 7, n=8, 7, 9, 6 | 71.6 International units per liter (IU/L) | Standard Deviation 20.18 |
| Placebo | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALT, Day 1, n=9, 9, 10, 9 | 15.6 International units per liter (IU/L) | Standard Deviation 10.36 |
| Placebo | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALT, Day 7, n=8, 7, 9, 6 | 15.9 International units per liter (IU/L) | Standard Deviation 6.85 |
| Placebo | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | AST, Day 1, n=9, 9, 10, 9 | 20.9 International units per liter (IU/L) | Standard Deviation 5.9 |
| Placebo | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | AST, Day 7, n=8, 7, 9, 6 | 19.3 International units per liter (IU/L) | Standard Deviation 6.16 |
| Placebo | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | GGT, Day 1, n=9, 9, 10, 9 | 31.3 International units per liter (IU/L) | Standard Deviation 20.62 |
| Placebo | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | GGT, Day 7, n=8, 7, 9, 6 | 29.9 International units per liter (IU/L) | Standard Deviation 18.88 |
| Cohort 1 UMEC 250 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | AST, Day 7, n=8, 7, 9, 6 | 19.4 International units per liter (IU/L) | Standard Deviation 4.31 |
| Cohort 1 UMEC 250 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | AST, Day 1, n=9, 9, 10, 9 | 18.9 International units per liter (IU/L) | Standard Deviation 3.48 |
| Cohort 1 UMEC 250 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALP, Day 7, n=8, 7, 9, 6 | 73.1 International units per liter (IU/L) | Standard Deviation 16.16 |
| Cohort 1 UMEC 250 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | GGT, Day 7, n=8, 7, 9, 6 | 24.7 International units per liter (IU/L) | Standard Deviation 6.78 |
| Cohort 1 UMEC 250 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | GGT, Day 1, n=9, 9, 10, 9 | 28.0 International units per liter (IU/L) | Standard Deviation 13.19 |
| Cohort 1 UMEC 250 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALT, Day 7, n=8, 7, 9, 6 | 15.6 International units per liter (IU/L) | Standard Deviation 7.11 |
| Cohort 1 UMEC 250 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALT, Day 1, n=9, 9, 10, 9 | 15.6 International units per liter (IU/L) | Standard Deviation 6.06 |
| Cohort 1 UMEC 250 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALP, Day 1, n=9, 9, 10, 9 | 76.8 International units per liter (IU/L) | Standard Deviation 15.11 |
| Cohort 2 UMEC 250 µg in Error | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | GGT, Day 1, n=9, 9, 10, 9 | 61.0 International units per liter (IU/L) | Standard Deviation 56.2 |
| Cohort 2 UMEC 250 µg in Error | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALT, Day 1, n=9, 9, 10, 9 | 24.2 International units per liter (IU/L) | Standard Deviation 9.66 |
| Cohort 2 UMEC 250 µg in Error | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALT, Day 7, n=8, 7, 9, 6 | 29.8 International units per liter (IU/L) | Standard Deviation 12.81 |
| Cohort 2 UMEC 250 µg in Error | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | AST, Day 1, n=9, 9, 10, 9 | 26.5 International units per liter (IU/L) | Standard Deviation 10.28 |
| Cohort 2 UMEC 250 µg in Error | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | AST, Day 7, n=8, 7, 9, 6 | 30.7 International units per liter (IU/L) | Standard Deviation 12.16 |
| Cohort 2 UMEC 250 µg in Error | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | GGT, Day 7, n=8, 7, 9, 6 | 66.0 International units per liter (IU/L) | Standard Deviation 68.81 |
| Cohort 2 UMEC 250 µg in Error | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALP, Day 1, n=9, 9, 10, 9 | 69.0 International units per liter (IU/L) | Standard Deviation 18.43 |
| Cohort 2 UMEC 250 µg in Error | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALP, Day 7, n=8, 7, 9, 6 | 71.1 International units per liter (IU/L) | Standard Deviation 16.47 |
| Cohort 3 UMEC 1000 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALT, Day 1, n=9, 9, 10, 9 | 18.6 International units per liter (IU/L) | Standard Deviation 9.49 |
| Cohort 3 UMEC 1000 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALT, Day 7, n=8, 7, 9, 6 | 20.7 International units per liter (IU/L) | Standard Deviation 9.85 |
| Cohort 3 UMEC 1000 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALP, Day 7, n=8, 7, 9, 6 | 67.7 International units per liter (IU/L) | Standard Deviation 18.15 |
| Cohort 3 UMEC 1000 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | ALP, Day 1, n=9, 9, 10, 9 | 63.8 International units per liter (IU/L) | Standard Deviation 20 |
| Cohort 3 UMEC 1000 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | AST, Day 1, n=9, 9, 10, 9 | 22.6 International units per liter (IU/L) | Standard Deviation 8.65 |
| Cohort 3 UMEC 1000 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | GGT, Day 7, n=8, 7, 9, 6 | 39.8 International units per liter (IU/L) | Standard Deviation 32.73 |
| Cohort 3 UMEC 1000 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | GGT, Day 1, n=9, 9, 10, 9 | 37.7 International units per liter (IU/L) | Standard Deviation 31.25 |
| Cohort 3 UMEC 1000 µg | Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 | AST, Day 7, n=8, 7, 9, 6 | 25.2 International units per liter (IU/L) | Standard Deviation 8.18 |
Primary
Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC), platelets, and white blood cell (WBC) count pre-dose on Day 1 and Day 7.
Time frame: Day 1 and Day 7
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Eosinophils, Day 7, n=9, 6, 9, 6 | 0.232 10^9 cells per liter (GI/L) | Standard Deviation 0.0793 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | WBC count, Day 7, n=9, 6, 9, 6 | 7.49 10^9 cells per liter (GI/L) | Standard Deviation 2.211 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Lymphocytes, Day 7, n=9, 6, 9, 6 | NA 10^9 cells per liter (GI/L) | — |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Lymphocytes, Day 1, n=9, 9, 10, 9 | NA 10^9 cells per liter (GI/L) | — |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | WBC count, Day 1, n=9, 9, 10, 9 | 8.06 10^9 cells per liter (GI/L) | Standard Deviation 2.22 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Platelets, Day 7, n=9, 6, 9, 6 | 271.8 10^9 cells per liter (GI/L) | Standard Deviation 53.73 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Basophils, Day 7, n=9, 6, 9, 6 | NA 10^9 cells per liter (GI/L) | — |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Platelets, Day 1, n=9, 9, 10, 9 | 278.1 10^9 cells per liter (GI/L) | Standard Deviation 66.25 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | ANC, Day 7, n=9, 6, 9, 6 | 4.706 10^9 cells per liter (GI/L) | Standard Deviation 1.8634 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | ANC, Day 1, n=9, 9, 10, 9 | 5.233 10^9 cells per liter (GI/L) | Standard Deviation 2.0968 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Eosinophils, Day 1, n=9, 9, 10, 9 | 0.248 10^9 cells per liter (GI/L) | Standard Deviation 0.1052 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Basophils, Day 1, n=9, 9, 10, 9 | NA 10^9 cells per liter (GI/L) | — |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Monocytes, Day 7, n=9, 6, 9, 6 | 0.448 10^9 cells per liter (GI/L) | Standard Deviation 0.1313 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Monocytes, Day 1, n=9, 9, 10, 9 | 0.510 10^9 cells per liter (GI/L) | Standard Deviation 0.1348 |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Basophils, Day 7, n=9, 6, 9, 6 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Basophils, Day 1, n=9, 9, 10, 9 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Eosinophils, Day 1, n=9, 9, 10, 9 | 0.319 10^9 cells per liter (GI/L) | Standard Deviation 0.1968 |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Eosinophils, Day 7, n=9, 6, 9, 6 | 0.280 10^9 cells per liter (GI/L) | Standard Deviation 0.1754 |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Lymphocytes, Day 1, n=9, 9, 10, 9 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Lymphocytes, Day 7, n=9, 6, 9, 6 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Monocytes, Day 1, n=9, 9, 10, 9 | 0.614 10^9 cells per liter (GI/L) | Standard Deviation 0.3648 |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Monocytes, Day 7, n=9, 6, 9, 6 | 0.562 10^9 cells per liter (GI/L) | Standard Deviation 0.2791 |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | ANC, Day 1, n=9, 9, 10, 9 | 5.306 10^9 cells per liter (GI/L) | Standard Deviation 1.3061 |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | ANC, Day 7, n=9, 6, 9, 6 | 5.023 10^9 cells per liter (GI/L) | Standard Deviation 1.4969 |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Platelets, Day 1, n=9, 9, 10, 9 | 238.2 10^9 cells per liter (GI/L) | Standard Deviation 39.71 |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Platelets, Day 7, n=9, 6, 9, 6 | 256.8 10^9 cells per liter (GI/L) | Standard Deviation 36.71 |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | WBC count, Day 1, n=9, 9, 10, 9 | 8.52 10^9 cells per liter (GI/L) | Standard Deviation 2.153 |
| Cohort 1 UMEC 250 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | WBC count, Day 7, n=9, 6, 9, 6 | 8.15 10^9 cells per liter (GI/L) | Standard Deviation 2.519 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Monocytes, Day 1, n=9, 9, 10, 9 | 0.607 10^9 cells per liter (GI/L) | Standard Deviation 0.1594 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Eosinophils, Day 1, n=9, 9, 10, 9 | 0.352 10^9 cells per liter (GI/L) | Standard Deviation 0.2951 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | WBC count, Day 7, n=9, 6, 9, 6 | 7.13 10^9 cells per liter (GI/L) | Standard Deviation 1.564 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Monocytes, Day 7, n=9, 6, 9, 6 | 0.657 10^9 cells per liter (GI/L) | Standard Deviation 0.1993 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | WBC count, Day 1, n=9, 9, 10, 9 | 7.11 10^9 cells per liter (GI/L) | Standard Deviation 1.692 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | ANC, Day 1, n=9, 9, 10, 9 | 4.244 10^9 cells per liter (GI/L) | Standard Deviation 1.3332 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Basophils, Day 7, n=9, 6, 9, 6 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | ANC, Day 7, n=9, 6, 9, 6 | 4.067 10^9 cells per liter (GI/L) | Standard Deviation 1.0184 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Platelets, Day 1, n=9, 9, 10, 9 | 254.7 10^9 cells per liter (GI/L) | Standard Deviation 51.04 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Lymphocytes, Day 1, n=9, 9, 10, 9 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Eosinophils, Day 7, n=9, 6, 9, 6 | 0.312 10^9 cells per liter (GI/L) | Standard Deviation 0.2672 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Platelets, Day 7, n=9, 6, 9, 6 | 255.1 10^9 cells per liter (GI/L) | Standard Deviation 61.42 |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Lymphocytes, Day 7, n=9, 6, 9, 6 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 2 UMEC 250 µg in Error | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Basophils, Day 1, n=9, 9, 10, 9 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Platelets, Day 7, n=9, 6, 9, 6 | 250.3 10^9 cells per liter (GI/L) | Standard Deviation 59.37 |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Monocytes, Day 1, n=9, 9, 10, 9 | 0.506 10^9 cells per liter (GI/L) | Standard Deviation 0.201 |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Eosinophils, Day 1, n=9, 9, 10, 9 | 0.144 10^9 cells per liter (GI/L) | Standard Deviation 0.091 |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Platelets, Day 1, n=9, 9, 10, 9 | 222.4 10^9 cells per liter (GI/L) | Standard Deviation 43.16 |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Basophils, Day 1, n=9, 9, 10, 9 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Monocytes, Day 7, n=9, 6, 9, 6 | 0.503 10^9 cells per liter (GI/L) | Standard Deviation 0.243 |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Basophils, Day 7, n=9, 6, 9, 6 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Eosinophils, Day 7, n=9, 6, 9, 6 | 0.153 10^9 cells per liter (GI/L) | Standard Deviation 0.0911 |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | WBC count, Day 7, n=9, 6, 9, 6 | 7.87 10^9 cells per liter (GI/L) | Standard Deviation 2.067 |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Lymphocytes, Day 7, n=9, 6, 9, 6 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | WBC count, Day 1, n=9, 9, 10, 9 | 7.56 10^9 cells per liter (GI/L) | Standard Deviation 2.572 |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | Lymphocytes, Day 1, n=9, 9, 10, 9 | NA 10^9 cells per liter (GI/L) | — |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | ANC, Day 7, n=9, 6, 9, 6 | 5.323 10^9 cells per liter (GI/L) | Standard Deviation 1.8539 |
| Cohort 3 UMEC 1000 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 | ANC, Day 1, n=9, 9, 10, 9 | 4.946 10^9 cells per liter (GI/L) | Standard Deviation 2.3879 |
Primary
Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7
Blood samples were collected for the measurement of calcium, glucose, potassium, sodium, and urea/BUN pre-dose on Day 1 and Day 7.
Time frame: Day 1 and Day 7
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Sodium, Day 1, n=9, 9, 10, 9 | 138.8 Millimoles per liter (mmol/L) | Standard Deviation 2.59 |
| Placebo | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Calcium, Day 7, n=8, 7, 9, 6 | 2.320 Millimoles per liter (mmol/L) | Standard Deviation 0.0454 |
| Placebo | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Potassium, Day 1, n=9, 9, 10, 9 | 4.67 Millimoles per liter (mmol/L) | Standard Deviation 0.472 |
| Placebo | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Glucose, Day 7, n=8, 7, 9, 6 | 5.25 Millimoles per liter (mmol/L) | Standard Deviation 0.746 |
| Placebo | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Glucose, Day 1, n=9, 9, 10, 9 | 5.16 Millimoles per liter (mmol/L) | Standard Deviation 0.937 |
| Placebo | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Calcium, Day 1, n=9, 9, 10, 9 | 2.317 Millimoles per liter (mmol/L) | Standard Deviation 0.0622 |
| Placebo | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Urea/BUN, Day 7, n=8, 7, 9, 6 | 5.15 Millimoles per liter (mmol/L) | Standard Deviation 1.032 |
| Placebo | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Sodium, Day 7, n=8, 7, 9, 6 | 140.4 Millimoles per liter (mmol/L) | Standard Deviation 2.88 |
| Placebo | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Potassium, Day 7, n=8, 7, 9, 6 | 4.58 Millimoles per liter (mmol/L) | Standard Deviation 0.276 |
| Placebo | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Urea/BUN, Day 1, n=9, 9, 10, 9 | 4.92 Millimoles per liter (mmol/L) | Standard Deviation 1.73 |
| Cohort 1 UMEC 250 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Sodium, Day 7, n=8, 7, 9, 6 | 140.0 Millimoles per liter (mmol/L) | Standard Deviation 1.15 |
| Cohort 1 UMEC 250 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Calcium, Day 1, n=9, 9, 10, 9 | 2.329 Millimoles per liter (mmol/L) | Standard Deviation 0.0697 |
| Cohort 1 UMEC 250 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Urea/BUN, Day 7, n=8, 7, 9, 6 | 5.51 Millimoles per liter (mmol/L) | Standard Deviation 0.691 |
| Cohort 1 UMEC 250 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Urea/BUN, Day 1, n=9, 9, 10, 9 | 5.29 Millimoles per liter (mmol/L) | Standard Deviation 0.842 |
| Cohort 1 UMEC 250 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Glucose, Day 1, n=9, 9, 10, 9 | 5.13 Millimoles per liter (mmol/L) | Standard Deviation 0.524 |
| Cohort 1 UMEC 250 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Glucose, Day 7, n=8, 7, 9, 6 | 5.10 Millimoles per liter (mmol/L) | Standard Deviation 0.792 |
| Cohort 1 UMEC 250 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Potassium, Day 1, n=9, 9, 10, 9 | 4.70 Millimoles per liter (mmol/L) | Standard Deviation 0.485 |
| Cohort 1 UMEC 250 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Potassium, Day 7, n=8, 7, 9, 6 | 4.74 Millimoles per liter (mmol/L) | Standard Deviation 0.431 |
| Cohort 1 UMEC 250 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Calcium, Day 7, n=8, 7, 9, 6 | 2.321 Millimoles per liter (mmol/L) | Standard Deviation 0.0308 |
| Cohort 1 UMEC 250 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Sodium, Day 1, n=9, 9, 10, 9 | 140.6 Millimoles per liter (mmol/L) | Standard Deviation 1.51 |
| Cohort 2 UMEC 250 µg in Error | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Glucose, Day 1, n=9, 9, 10, 9 | 5.38 Millimoles per liter (mmol/L) | Standard Deviation 0.751 |
| Cohort 2 UMEC 250 µg in Error | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Urea/BUN, Day 7, n=8, 7, 9, 6 | 5.70 Millimoles per liter (mmol/L) | Standard Deviation 1.562 |
| Cohort 2 UMEC 250 µg in Error | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Sodium, Day 1, n=9, 9, 10, 9 | 140.6 Millimoles per liter (mmol/L) | Standard Deviation 2.27 |
| Cohort 2 UMEC 250 µg in Error | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Potassium, Day 7, n=8, 7, 9, 6 | 4.48 Millimoles per liter (mmol/L) | Standard Deviation 0.519 |
| Cohort 2 UMEC 250 µg in Error | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Calcium, Day 7, n=8, 7, 9, 6 | 2.370 Millimoles per liter (mmol/L) | Standard Deviation 0.1411 |
| Cohort 2 UMEC 250 µg in Error | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Urea/BUN, Day 1, n=9, 9, 10, 9 | 5.77 Millimoles per liter (mmol/L) | Standard Deviation 1.854 |
| Cohort 2 UMEC 250 µg in Error | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Glucose, Day 7, n=8, 7, 9, 6 | 5.84 Millimoles per liter (mmol/L) | Standard Deviation 0.948 |
| Cohort 2 UMEC 250 µg in Error | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Calcium, Day 1, n=9, 9, 10, 9 | 2.342 Millimoles per liter (mmol/L) | Standard Deviation 0.1215 |
| Cohort 2 UMEC 250 µg in Error | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Sodium, Day 7, n=8, 7, 9, 6 | 140.2 Millimoles per liter (mmol/L) | Standard Deviation 2.44 |
| Cohort 2 UMEC 250 µg in Error | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Potassium, Day 1, n=9, 9, 10, 9 | 4.50 Millimoles per liter (mmol/L) | Standard Deviation 0.579 |
| Cohort 3 UMEC 1000 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Urea/BUN, Day 7, n=8, 7, 9, 6 | 5.88 Millimoles per liter (mmol/L) | Standard Deviation 3.02 |
| Cohort 3 UMEC 1000 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Calcium, Day 1, n=9, 9, 10, 9 | 2.311 Millimoles per liter (mmol/L) | Standard Deviation 0.0807 |
| Cohort 3 UMEC 1000 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Calcium, Day 7, n=8, 7, 9, 6 | 2.343 Millimoles per liter (mmol/L) | Standard Deviation 0.0631 |
| Cohort 3 UMEC 1000 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Glucose, Day 1, n=9, 9, 10, 9 | 5.26 Millimoles per liter (mmol/L) | Standard Deviation 0.921 |
| Cohort 3 UMEC 1000 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Glucose, Day 7, n=8, 7, 9, 6 | 5.42 Millimoles per liter (mmol/L) | Standard Deviation 0.717 |
| Cohort 3 UMEC 1000 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Potassium, Day 1, n=9, 9, 10, 9 | 4.36 Millimoles per liter (mmol/L) | Standard Deviation 0.364 |
| Cohort 3 UMEC 1000 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Potassium, Day 7, n=8, 7, 9, 6 | 4.45 Millimoles per liter (mmol/L) | Standard Deviation 0.428 |
| Cohort 3 UMEC 1000 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Sodium, Day 1, n=9, 9, 10, 9 | 139.6 Millimoles per liter (mmol/L) | Standard Deviation 1.59 |
| Cohort 3 UMEC 1000 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Sodium, Day 7, n=8, 7, 9, 6 | 139.2 Millimoles per liter (mmol/L) | Standard Deviation 2.4 |
| Cohort 3 UMEC 1000 µg | Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 | Urea/BUN, Day 1, n=9, 9, 10, 9 | 5.72 Millimoles per liter (mmol/L) | Standard Deviation 2.44 |
Primary
Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7
Blood samples were collected for the measurement of direct bilirubin, total bilirubin, and creatinine at pre-dose on Day 1 and Day 7.
Time frame: Day 1 and Day 7
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Creatinine, Day 1, n=9, 9, 10, 9 | 76.2 Micromoles per liter (µmol/L) | Standard Deviation 12.15 |
| Placebo | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Direct bilirubin, Day 7, n=5, 7, 9 | 2.0 Micromoles per liter (µmol/L) | Standard Deviation 1.41 |
| Placebo | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Creatinine, Day 7, n=8, 7, 9, 6 | 78.8 Micromoles per liter (µmol/L) | Standard Deviation 10.53 |
| Placebo | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Total bilirubin, Day 1, n=9, 9, 10, 9 | 10.8 Micromoles per liter (µmol/L) | Standard Deviation 4.44 |
| Placebo | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Total bilirubin, Day 7, n=8, 7, 9, 6 | 9.3 Micromoles per liter (µmol/L) | Standard Deviation 4.03 |
| Placebo | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Direct bilirubin, Day 1, n=6, 9, 10 | 2.3 Micromoles per liter (µmol/L) | Standard Deviation 1.97 |
| Cohort 1 UMEC 250 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Total bilirubin, Day 1, n=9, 9, 10, 9 | 8.2 Micromoles per liter (µmol/L) | Standard Deviation 1.2 |
| Cohort 1 UMEC 250 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Direct bilirubin, Day 1, n=6, 9, 10 | 1.7 Micromoles per liter (µmol/L) | Standard Deviation 0.5 |
| Cohort 1 UMEC 250 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Creatinine, Day 1, n=9, 9, 10, 9 | 84.3 Micromoles per liter (µmol/L) | Standard Deviation 15.64 |
| Cohort 1 UMEC 250 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Total bilirubin, Day 7, n=8, 7, 9, 6 | 9.9 Micromoles per liter (µmol/L) | Standard Deviation 2.27 |
| Cohort 1 UMEC 250 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Creatinine, Day 7, n=8, 7, 9, 6 | 80.1 Micromoles per liter (µmol/L) | Standard Deviation 14.37 |
| Cohort 1 UMEC 250 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Direct bilirubin, Day 7, n=5, 7, 9 | 2.0 Micromoles per liter (µmol/L) | Standard Deviation 0.58 |
| Cohort 2 UMEC 250 µg in Error | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Creatinine, Day 7, n=8, 7, 9, 6 | 82.6 Micromoles per liter (µmol/L) | Standard Deviation 12.83 |
| Cohort 2 UMEC 250 µg in Error | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Direct bilirubin, Day 7, n=5, 7, 9 | 2.2 Micromoles per liter (µmol/L) | Standard Deviation 0.67 |
| Cohort 2 UMEC 250 µg in Error | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Total bilirubin, Day 7, n=8, 7, 9, 6 | 10.8 Micromoles per liter (µmol/L) | Standard Deviation 3.11 |
| Cohort 2 UMEC 250 µg in Error | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Total bilirubin, Day 1, n=9, 9, 10, 9 | 10.9 Micromoles per liter (µmol/L) | Standard Deviation 4.01 |
| Cohort 2 UMEC 250 µg in Error | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Direct bilirubin, Day 1, n=6, 9, 10 | 2.0 Micromoles per liter (µmol/L) | Standard Deviation 1.15 |
| Cohort 2 UMEC 250 µg in Error | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Creatinine, Day 1, n=9, 9, 10, 9 | 80.1 Micromoles per liter (µmol/L) | Standard Deviation 14.26 |
| Cohort 3 UMEC 1000 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Creatinine, Day 7, n=8, 7, 9, 6 | 93.0 Micromoles per liter (µmol/L) | Standard Deviation 39.8 |
| Cohort 3 UMEC 1000 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Direct bilirubin, Day 1, n=6, 9, 10 | NA Micromoles per liter (µmol/L) | — |
| Cohort 3 UMEC 1000 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Direct bilirubin, Day 7, n=5, 7, 9 | NA Micromoles per liter (µmol/L) | — |
| Cohort 3 UMEC 1000 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Total bilirubin, Day 1, n=9, 9, 10, 9 | 10.2 Micromoles per liter (µmol/L) | Standard Deviation 3.03 |
| Cohort 3 UMEC 1000 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Total bilirubin, Day 7, n=8, 7, 9, 6 | 11.0 Micromoles per liter (µmol/L) | Standard Deviation 3.16 |
| Cohort 3 UMEC 1000 µg | Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 | Creatinine, Day 1, n=9, 9, 10, 9 | 87.0 Micromoles per liter (µmol/L) | Standard Deviation 33.59 |
Primary
Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7
Maximum heart rate (Max HR) and mean HR from 0-24 hour Holter monitoring on treatment Day 7 were derived. The analysis was adjusted for treatment and Baseline, where Baseline is defined as the corresponding summary measure (i.e., mean heart rate \[0-24 hours\] or maximum heart rate \[0-24 hours\]) from screening records.
Time frame: Day 7
Population: All Subjects Population. The number of participants presented represent those with data available at the time point being presented; however, all participants in the ASP without missing covariate information are included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7 | Max HR | 125.19 Beats per minute | Standard Error 4.744 |
| Placebo | Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7 | Mean HR | 77.47 Beats per minute | Standard Error 1.896 |
| Cohort 1 UMEC 250 µg | Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7 | Mean HR | 75.94 Beats per minute | Standard Error 2.306 |
| Cohort 1 UMEC 250 µg | Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7 | Max HR | 134.08 Beats per minute | Standard Error 5.81 |
| Cohort 2 UMEC 250 µg in Error | Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7 | Max HR | 127.48 Beats per minute | Standard Error 4.724 |
| Cohort 2 UMEC 250 µg in Error | Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7 | Mean HR | 75.96 Beats per minute | Standard Error 1.888 |
| Cohort 3 UMEC 1000 µg | Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7 | Max HR | 126.91 Beats per minute | Standard Error 5.785 |
| Cohort 3 UMEC 1000 µg | Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7 | Mean HR | 76.75 Beats per minute | Standard Error 2.312 |
Primary
Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7
Maximum heart rate (Max HR) and weighted mean (WM) from 0-4 hour on Days 1 and 7 were derived. Max HR (0-4 h) is defined as the maximum heart rate attained within 0-4 h. The weighted mean HR (0-4 h) was derived by calculating the area under the curve, and then dividing the value by the relevant time interval. Each of the maximum and weighted mean (0-4h) endpoints for heart rate, was statistically analyzed using a mixed effects model. The terms treatment, baseline, day and any relevant interactions were considered in the model. Least squares means are adjusted for treatment, Baseline, day, treatment by Baseline and Baseline by day interaction, where Baseline is defined as the mean of the three pre-dose assessments.
Time frame: Day 1 and Day 7
Population: All Subjects Population (ASP). The number of participants presented represent those with data available at the time point being presented; however, all participants in the ASP without missing covariate information are included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 1, Max HR, n=9, 10, 10, 9 | 68.30 Beats per minute | Standard Error 2.009 |
| Placebo | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 7, Max HR, n=9, 7, 9, 6 | 68.99 Beats per minute | Standard Error 1.917 |
| Placebo | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 1, WM, n=9, 9, 10, 9 | 63.84 Beats per minute | Standard Error 1.582 |
| Placebo | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 7, WM, n=9, 7, 9, 6 | 64.83 Beats per minute | Standard Error 1.682 |
| Cohort 1 UMEC 250 µg | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 7, Max HR, n=9, 7, 9, 6 | 70.24 Beats per minute | Standard Error 2.203 |
| Cohort 1 UMEC 250 µg | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 1, WM, n=9, 9, 10, 9 | 63.62 Beats per minute | Standard Error 1.584 |
| Cohort 1 UMEC 250 µg | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 7, WM, n=9, 7, 9, 6 | 64.98 Beats per minute | Standard Error 1.874 |
| Cohort 1 UMEC 250 µg | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 1, Max HR, n=9, 10, 10, 9 | 70.56 Beats per minute | Standard Error 1.91 |
| Cohort 2 UMEC 250 µg in Error | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 1, WM, n=9, 9, 10, 9 | 66.17 Beats per minute | Standard Error 1.514 |
| Cohort 2 UMEC 250 µg in Error | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 7, Max HR, n=9, 7, 9, 6 | 66.74 Beats per minute | Standard Error 1.964 |
| Cohort 2 UMEC 250 µg in Error | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 7, WM, n=9, 7, 9, 6 | 62.32 Beats per minute | Standard Error 1.698 |
| Cohort 2 UMEC 250 µg in Error | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 1, Max HR, n=9, 10, 10, 9 | 71.57 Beats per minute | Standard Error 1.924 |
| Cohort 3 UMEC 1000 µg | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 7, WM, n=9, 7, 9, 6 | 71.89 Beats per minute | Standard Error 2.026 |
| Cohort 3 UMEC 1000 µg | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 7, Max HR, n=9, 7, 9, 6 | 77.69 Beats per minute | Standard Error 2.398 |
| Cohort 3 UMEC 1000 µg | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 1, Max HR, n=9, 10, 10, 9 | 75.79 Beats per minute | Standard Error 2.066 |
| Cohort 3 UMEC 1000 µg | Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 | Day 1, WM, n=9, 9, 10, 9 | 70.00 Beats per minute | Standard Error 1.627 |
95% CI: [-3.39, 7.91]
95% CI: [-4.78, 7.28]
95% CI: [-2.37, 8.91]
95% CI: [-7.89, 3.39]
95% CI: [1.59, 13.39]
95% CI: [2.34, 15.05]
95% CI: [-4.8, 4.34]
95% CI: [-5.09, 5.4]
95% CI: [-2.12, 6.77]
95% CI: [-7.48, 2.45]
95% CI: [1.51, 10.81]
95% CI: [1.57, 12.54]
Primary
Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7
Blood samples were collected for the measurement of MCH pre-dose on Day 1 and Day 7.
Time frame: Day 1 and Day 7
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7 | Day 1, n=9, 9, 10, 9 | 31.92 picograms/cell (pg) | Standard Deviation 1.711 |
| Placebo | Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7 | Day 7, n=9, 6, 9, 6 | 31.71 picograms/cell (pg) | Standard Deviation 1.661 |
| Cohort 1 UMEC 250 µg | Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7 | Day 1, n=9, 9, 10, 9 | 32.44 picograms/cell (pg) | Standard Deviation 2.371 |
| Cohort 1 UMEC 250 µg | Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7 | Day 7, n=9, 6, 9, 6 | 32.20 picograms/cell (pg) | Standard Deviation 2.871 |
| Cohort 2 UMEC 250 µg in Error | Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7 | Day 1, n=9, 9, 10, 9 | 31.25 picograms/cell (pg) | Standard Deviation 1.978 |
| Cohort 2 UMEC 250 µg in Error | Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7 | Day 7, n=9, 6, 9, 6 | 31.22 picograms/cell (pg) | Standard Deviation 1.999 |
| Cohort 3 UMEC 1000 µg | Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7 | Day 7, n=9, 6, 9, 6 | 31.95 picograms/cell (pg) | Standard Deviation 2.146 |
| Cohort 3 UMEC 1000 µg | Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7 | Day 1, n=9, 9, 10, 9 | 31.70 picograms/cell (pg) | Standard Deviation 1.859 |
Primary
Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7
Blood samples were collected for the measurement of MCV pre-dose on Day 1 and Day 7.
Time frame: Day 1 and Day 7
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7 | Day 1, n=9, 9, 10, 9 | 93.9 10^-15 liters (femtoliters) | Standard Deviation 3.66 |
| Placebo | Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7 | Day 7, n=9, 6, 9, 6 | 94.0 10^-15 liters (femtoliters) | Standard Deviation 3.5 |
| Cohort 1 UMEC 250 µg | Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7 | Day 7, n=9, 6, 9, 6 | 94.5 10^-15 liters (femtoliters) | Standard Deviation 7.12 |
| Cohort 1 UMEC 250 µg | Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7 | Day 1, n=9, 9, 10, 9 | 95.9 10^-15 liters (femtoliters) | Standard Deviation 7.06 |
| Cohort 2 UMEC 250 µg in Error | Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7 | Day 1, n=9, 9, 10, 9 | 91.9 10^-15 liters (femtoliters) | Standard Deviation 4.93 |
| Cohort 2 UMEC 250 µg in Error | Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7 | Day 7, n=9, 6, 9, 6 | 92.6 10^-15 liters (femtoliters) | Standard Deviation 5.34 |
| Cohort 3 UMEC 1000 µg | Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7 | Day 1, n=9, 9, 10, 9 | 94.0 10^-15 liters (femtoliters) | Standard Deviation 5.32 |
| Cohort 3 UMEC 1000 µg | Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7 | Day 7, n=9, 6, 9, 6 | 94.8 10^-15 liters (femtoliters) | Standard Deviation 5.49 |
Primary
Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured at Screening, pre-dose, and 4 hours (hr) post-dose on Day 1 and Day 7. FEV1 tests were repeated until three technically acceptable measurements were made.
Time frame: Screening, Day 1, and Day 7
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 7, pre-dose, n=9, 7, 9, 6 | 1.263 Liters | Standard Deviation 0.4695 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 1, pre-dose, n=9, 10, 10, 9 | 1.294 Liters | Standard Deviation 0.4642 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 7, 4 hr post-dose, n=9, 7, 9, 6 | 1.250 Liters | Standard Deviation 0.5143 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 1, 4 hr post-dose, n=9, 9, 10, 9 | 1.309 Liters | Standard Deviation 0.4333 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Screening, n=9, 10, 10, 9 | 1.556 Liters | Standard Deviation 0.6315 |
| Cohort 1 UMEC 250 µg | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 1, 4 hr post-dose, n=9, 9, 10, 9 | 1.250 Liters | Standard Deviation 0.3934 |
| Cohort 1 UMEC 250 µg | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 7, pre-dose, n=9, 7, 9, 6 | 1.153 Liters | Standard Deviation 0.4066 |
| Cohort 1 UMEC 250 µg | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 7, 4 hr post-dose, n=9, 7, 9, 6 | 1.181 Liters | Standard Deviation 0.3875 |
| Cohort 1 UMEC 250 µg | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 1, pre-dose, n=9, 10, 10, 9 | 1.059 Liters | Standard Deviation 0.3509 |
| Cohort 1 UMEC 250 µg | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Screening, n=9, 10, 10, 9 | 1.253 Liters | Standard Deviation 0.4338 |
| Cohort 2 UMEC 250 µg in Error | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 1, 4 hr post-dose, n=9, 9, 10, 9 | 1.565 Liters | Standard Deviation 0.5858 |
| Cohort 2 UMEC 250 µg in Error | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Screening, n=9, 10, 10, 9 | 1.562 Liters | Standard Deviation 0.5066 |
| Cohort 2 UMEC 250 µg in Error | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 1, pre-dose, n=9, 10, 10, 9 | 1.443 Liters | Standard Deviation 0.484 |
| Cohort 2 UMEC 250 µg in Error | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 7, pre-dose, n=9, 7, 9, 6 | 1.593 Liters | Standard Deviation 0.5425 |
| Cohort 2 UMEC 250 µg in Error | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 7, 4 hr post-dose, n=9, 7, 9, 6 | 1.564 Liters | Standard Deviation 0.5476 |
| Cohort 3 UMEC 1000 µg | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 7, pre-dose, n=9, 7, 9, 6 | 1.483 Liters | Standard Deviation 0.3055 |
| Cohort 3 UMEC 1000 µg | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 1, pre-dose, n=9, 10, 10, 9 | 1.289 Liters | Standard Deviation 0.2968 |
| Cohort 3 UMEC 1000 µg | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Screening, n=9, 10, 10, 9 | 1.364 Liters | Standard Deviation 0.3504 |
| Cohort 3 UMEC 1000 µg | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 1, 4 hr post-dose, n=9, 9, 10, 9 | 1.534 Liters | Standard Deviation 0.3389 |
| Cohort 3 UMEC 1000 µg | Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 | Day 7, 4 hr post-dose, n=9, 7, 9, 6 | 1.517 Liters | Standard Deviation 0.2685 |
Primary
Mean Heart Rate (HR) on Days 1 and 7
HR was measured in a semi-recumbent position at approximately 45 degrees after the participant was kept at rest for at least 5 minutes. HR was obtained at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose (PD) on Day 1 and at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr PD on Day 7.
Time frame: Day 1 (pre-dose and 15 minutes [min], 45 min, 1.5 hours [hr], 4 hr, and 8 hr post-dose) and Day 7 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr post-dose)
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, pre-dose, n=9, 10, 10, 9 | 70.9 Beats per minute | Standard Deviation 11.09 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 15 min PD, n=9, 9, 10, 8 | 68.2 Beats per minute | Standard Deviation 10.28 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 45 min PD, n=9, 9, 10, 9 | 66.0 Beats per minute | Standard Deviation 9.33 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 63.3 Beats per minute | Standard Deviation 9.42 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 4 hr PD, n=9, 9, 10, 9 | 64.0 Beats per minute | Standard Deviation 10.37 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 8 hr PD, n=9, 9, 10, 9 | 72.6 Beats per minute | Standard Deviation 9.93 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, pre-dose, n=9, 7, 9, 6 | 70.1 Beats per minute | Standard Deviation 7.9 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 15 min PD, n=9, 7, 9, 6 | 67.0 Beats per minute | Standard Deviation 6.61 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 45 min PD, n=9, 6, 9, 6 | 66.8 Beats per minute | Standard Deviation 9.16 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 65.3 Beats per minute | Standard Deviation 7.86 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 4 hr PD, n=9, 7, 9, 6 | 64.1 Beats per minute | Standard Deviation 7.61 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 8 hr PD, n=9, 7, 9, 6 | 74.8 Beats per minute | Standard Deviation 6.83 |
| Placebo | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 24 hr PD, n=9, 7, 9, 6 | 73.8 Beats per minute | Standard Deviation 7 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 60.7 Beats per minute | Standard Deviation 12.06 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 24 hr PD, n=9, 7, 9, 6 | 75.6 Beats per minute | Standard Deviation 11.5 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 4 hr PD, n=9, 7, 9, 6 | 62.7 Beats per minute | Standard Deviation 7.74 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 15 min PD, n=9, 7, 9, 6 | 69.4 Beats per minute | Standard Deviation 12.16 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 45 min PD, n=9, 9, 10, 9 | 62.3 Beats per minute | Standard Deviation 10.9 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, pre-dose, n=9, 10, 10, 9 | 68.3 Beats per minute | Standard Deviation 10.42 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 64.0 Beats per minute | Standard Deviation 10.92 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 45 min PD, n=9, 6, 9, 6 | 66.3 Beats per minute | Standard Deviation 11.88 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 8 hr PD, n=9, 9, 10, 9 | 67.4 Beats per minute | Standard Deviation 9.62 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 4 hr PD, n=9, 9, 10, 9 | 62.0 Beats per minute | Standard Deviation 10.31 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 15 min PD, n=9, 9, 10, 8 | 67.4 Beats per minute | Standard Deviation 11.28 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 8 hr PD, n=9, 7, 9, 6 | 71.0 Beats per minute | Standard Deviation 8.6 |
| Cohort 1 UMEC 250 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, pre-dose, n=9, 7, 9, 6 | 71.3 Beats per minute | Standard Deviation 12.64 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 4 hr PD, n=9, 7, 9, 6 | 62.6 Beats per minute | Standard Deviation 9.79 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 65.8 Beats per minute | Standard Deviation 10.3 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 4 hr PD, n=9, 9, 10, 9 | 70.2 Beats per minute | Standard Deviation 10.74 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 24 hr PD, n=9, 7, 9, 6 | 72.6 Beats per minute | Standard Deviation 8.97 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 8 hr PD, n=9, 9, 10, 9 | 77.2 Beats per minute | Standard Deviation 11.73 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, pre-dose, n=9, 7, 9, 6 | 71.4 Beats per minute | Standard Deviation 14.01 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 8 hr PD, n=9, 7, 9, 6 | 74.8 Beats per minute | Standard Deviation 8.91 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 15 min PD, n=9, 7, 9, 6 | 68.9 Beats per minute | Standard Deviation 12.19 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 45 min PD, n=9, 6, 9, 6 | 66.6 Beats per minute | Standard Deviation 10.98 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 63.8 Beats per minute | Standard Deviation 8.96 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, pre-dose, n=9, 10, 10, 9 | 72.8 Beats per minute | Standard Deviation 11.69 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 15 min PD, n=9, 9, 10, 8 | 71.4 Beats per minute | Standard Deviation 9.86 |
| Cohort 2 UMEC 250 µg in Error | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 45 min PD, n=9, 9, 10, 9 | 70.2 Beats per minute | Standard Deviation 11.95 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 67.7 Beats per minute | Standard Deviation 11.13 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 15 min PD, n=9, 7, 9, 6 | 74.8 Beats per minute | Standard Deviation 9.39 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 64.2 Beats per minute | Standard Deviation 11.05 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, pre-dose, n=9, 10, 10, 9 | 64.7 Beats per minute | Standard Deviation 10.34 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, pre-dose, n=9, 7, 9, 6 | 69.7 Beats per minute | Standard Deviation 10.51 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 8 hr PD, n=9, 9, 10, 9 | 74.4 Beats per minute | Standard Deviation 7.35 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 45 min PD, n=9, 9, 10, 9 | 66.4 Beats per minute | Standard Deviation 14.78 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 15 min PD, n=9, 9, 10, 8 | 72.3 Beats per minute | Standard Deviation 13.56 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 1, 4 hr PD, n=9, 9, 10, 9 | 65.7 Beats per minute | Standard Deviation 10.2 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 45 min PD, n=9, 6, 9, 6 | 70.0 Beats per minute | Standard Deviation 10 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 24 hr PD, n=9, 7, 9, 6 | 70.8 Beats per minute | Standard Deviation 9.89 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 8 hr PD, n=9, 7, 9, 6 | 73.8 Beats per minute | Standard Deviation 7.41 |
| Cohort 3 UMEC 1000 µg | Mean Heart Rate (HR) on Days 1 and 7 | Day 7, 4 hr PD, n=9, 7, 9, 6 | 67.5 Beats per minute | Standard Deviation 7.5 |
Primary
Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7
Blood pressure was measured in a semi-recumbent position at approximately 45 degrees after the participant was kept at rest for at least 5 minutes. SBP and DBP were obtained at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose (PD) on Day 1 and at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr PD on Day 7.
Time frame: Day 1 (pre-dose and 15 minutes [min], 45 min, 1.5 hours [hr], 4 hr, and 8 hr post-dose) and Day 7 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr post-dose)
Population: All Subjects Population (ASP). Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, pre-dose, n=9, 10, 10, 9 | 81.6 Millimeters of mercury (mmHg) | Standard Deviation 8.52 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 24 hr PD, n=9, 7, 9, 6 | 132.1 Millimeters of mercury (mmHg) | Standard Deviation 9.49 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 15 min PD, n=9, 7, 9, 6 | 141.3 Millimeters of mercury (mmHg) | Standard Deviation 13.95 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 82.2 Millimeters of mercury (mmHg) | Standard Deviation 9.91 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 8 hr PD, n=9, 7, 9, 6 | 136.1 Millimeters of mercury (mmHg) | Standard Deviation 13.17 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 4 hr PD, n=9, 7, 9, 6 | 139.4 Millimeters of mercury (mmHg) | Standard Deviation 12.91 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 45 min PD, n=9, 7, 9, 6 | 139.7 Millimeters of mercury (mmHg) | Standard Deviation 13.93 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 45 min PD, n=9, 9, 10, 9 | 133.3 Millimeters of mercury (mmHg) | Standard Deviation 9.35 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 137.8 Millimeters of mercury (mmHg) | Standard Deviation 15.34 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 8 hr PD, n=9, 7, 9, 6 | 76.2 Millimeters of mercury (mmHg) | Standard Deviation 8.7 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 45 min PD, n=9, 7, 9, 6 | 80.6 Millimeters of mercury (mmHg) | Standard Deviation 10.36 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 15 min PD, n=9, 7, 9, 6 | 82.8 Millimeters of mercury (mmHg) | Standard Deviation 11.78 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 140.0 Millimeters of mercury (mmHg) | Standard Deviation 19.42 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, pre-dose, n=9, 10, 10, 9 | 138.9 Millimeters of mercury (mmHg) | Standard Deviation 11.43 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, pre-dose, n=9, 7, 9, 6 | 78.7 Millimeters of mercury (mmHg) | Standard Deviation 8.64 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 8 hr PD, n=9, 9, 10, 9 | 77.8 Millimeters of mercury (mmHg) | Standard Deviation 8.67 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 4 hr PD, n=9, 9, 10, 9 | 141.0 Millimeters of mercury (mmHg) | Standard Deviation 15.41 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 15 min PD, n=9, 9, 10, 8 | 135.1 Millimeters of mercury (mmHg) | Standard Deviation 12.96 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 4 hr PD, n=9, 9, 10, 9 | 83.4 Millimeters of mercury (mmHg) | Standard Deviation 11.14 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 79.3 Millimeters of mercury (mmHg) | Standard Deviation 8.54 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 8 hr PD, n=9, 9, 10, 9 | 134.8 Millimeters of mercury (mmHg) | Standard Deviation 12.22 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 24 hr PD, n=9, 7, 9, 6 | 78.2 Millimeters of mercury (mmHg) | Standard Deviation 8.87 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 45 min PD, n=9, 9, 10, 9 | 78.9 Millimeters of mercury (mmHg) | Standard Deviation 8.85 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 15 min PD, n=9, 9, 10, 8 | 79.6 Millimeters of mercury (mmHg) | Standard Deviation 9.76 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, pre-dose, n=9, 7, 9, 6 | 134.3 Millimeters of mercury (mmHg) | Standard Deviation 9.16 |
| Placebo | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 4 hr PD, n=9, 7, 9, 6 | 79.0 Millimeters of mercury (mmHg) | Standard Deviation 8.97 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 138.2 Millimeters of mercury (mmHg) | Standard Deviation 15.79 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, pre-dose, n=9, 10, 10, 9 | 132.8 Millimeters of mercury (mmHg) | Standard Deviation 11.97 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 15 min PD, n=9, 9, 10, 8 | 134.9 Millimeters of mercury (mmHg) | Standard Deviation 15.05 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 45 min PD, n=9, 9, 10, 9 | 135.8 Millimeters of mercury (mmHg) | Standard Deviation 14.63 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 4 hr PD, n=9, 9, 10, 9 | 139.4 Millimeters of mercury (mmHg) | Standard Deviation 21.43 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 8 hr PD, n=9, 9, 10, 9 | 135.7 Millimeters of mercury (mmHg) | Standard Deviation 15.28 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, pre-dose, n=9, 7, 9, 6 | 131.8 Millimeters of mercury (mmHg) | Standard Deviation 14.47 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 15 min PD, n=9, 7, 9, 6 | 134.4 Millimeters of mercury (mmHg) | Standard Deviation 15.54 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 45 min PD, n=9, 7, 9, 6 | 135.4 Millimeters of mercury (mmHg) | Standard Deviation 19.08 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 141.6 Millimeters of mercury (mmHg) | Standard Deviation 18.35 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 4 hr PD, n=9, 7, 9, 6 | 139.6 Millimeters of mercury (mmHg) | Standard Deviation 15.18 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 8 hr PD, n=9, 7, 9, 6 | 129.4 Millimeters of mercury (mmHg) | Standard Deviation 14.32 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 24 hr PD, n=9, 7, 9, 6 | 135.7 Millimeters of mercury (mmHg) | Standard Deviation 9.39 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, pre-dose, n=9, 10, 10, 9 | 79.0 Millimeters of mercury (mmHg) | Standard Deviation 6.69 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 15 min PD, n=9, 9, 10, 8 | 83.6 Millimeters of mercury (mmHg) | Standard Deviation 7.47 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 45 min PD, n=9, 9, 10, 9 | 79.6 Millimeters of mercury (mmHg) | Standard Deviation 9.58 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 82.3 Millimeters of mercury (mmHg) | Standard Deviation 9.26 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 4 hr PD, n=9, 9, 10, 9 | 81.0 Millimeters of mercury (mmHg) | Standard Deviation 10.91 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 8 hr PD, n=9, 9, 10, 9 | 79.9 Millimeters of mercury (mmHg) | Standard Deviation 8.85 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, pre-dose, n=9, 7, 9, 6 | 82.6 Millimeters of mercury (mmHg) | Standard Deviation 8.85 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 15 min PD, n=9, 7, 9, 6 | 82.7 Millimeters of mercury (mmHg) | Standard Deviation 9.11 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 45 min PD, n=9, 7, 9, 6 | 81.4 Millimeters of mercury (mmHg) | Standard Deviation 9.45 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 82.6 Millimeters of mercury (mmHg) | Standard Deviation 8.9 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 4 hr PD, n=9, 7, 9, 6 | 84.0 Millimeters of mercury (mmHg) | Standard Deviation 7.68 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 8 hr PD, n=9, 7, 9, 6 | 77.1 Millimeters of mercury (mmHg) | Standard Deviation 11.51 |
| Cohort 1 UMEC 250 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 24 hr PD, n=9, 7, 9, 6 | 81.6 Millimeters of mercury (mmHg) | Standard Deviation 9.05 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, pre-dose, n=9, 7, 9, 6 | 139.3 Millimeters of mercury (mmHg) | Standard Deviation 10.59 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, pre-dose, n=9, 10, 10, 9 | 82.1 Millimeters of mercury (mmHg) | Standard Deviation 7.63 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 15 min PD, n=9, 9, 10, 8 | 137.7 Millimeters of mercury (mmHg) | Standard Deviation 9.94 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 15 min PD, n=9, 9, 10, 8 | 81.4 Millimeters of mercury (mmHg) | Standard Deviation 7.71 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 8 hr PD, n=9, 9, 10, 9 | 140.8 Millimeters of mercury (mmHg) | Standard Deviation 13.14 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 45 min PD, n=9, 9, 10, 9 | 82.8 Millimeters of mercury (mmHg) | Standard Deviation 9.96 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 4 hr PD, n=9, 7, 9, 6 | 83.0 Millimeters of mercury (mmHg) | Standard Deviation 8.09 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 84.0 Millimeters of mercury (mmHg) | Standard Deviation 6.55 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 4 hr PD, n=9, 9, 10, 9 | 141.6 Millimeters of mercury (mmHg) | Standard Deviation 8.86 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 4 hr PD, n=9, 9, 10, 9 | 83.1 Millimeters of mercury (mmHg) | Standard Deviation 11.13 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 8 hr PD, n=9, 9, 10, 9 | 80.5 Millimeters of mercury (mmHg) | Standard Deviation 7.84 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 142.1 Millimeters of mercury (mmHg) | Standard Deviation 12.91 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 24 hr PD, n=9, 7, 9, 6 | 81.7 Millimeters of mercury (mmHg) | Standard Deviation 9.7 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, pre-dose, n=9, 7, 9, 6 | 85.8 Millimeters of mercury (mmHg) | Standard Deviation 7.79 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 8 hr PD, n=9, 7, 9, 6 | 80.7 Millimeters of mercury (mmHg) | Standard Deviation 7.45 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 15 min PD, n=9, 7, 9, 6 | 82.9 Millimeters of mercury (mmHg) | Standard Deviation 9.29 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 45 min PD, n=9, 9, 10, 9 | 133.9 Millimeters of mercury (mmHg) | Standard Deviation 11.28 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 45 min PD, n=9, 7, 9, 6 | 82.4 Millimeters of mercury (mmHg) | Standard Deviation 7.04 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 45 min PD, n=9, 7, 9, 6 | 135.8 Millimeters of mercury (mmHg) | Standard Deviation 9.28 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 141.3 Millimeters of mercury (mmHg) | Standard Deviation 10.9 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 4 hr PD, n=9, 7, 9, 6 | 141.6 Millimeters of mercury (mmHg) | Standard Deviation 8.56 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 15 min PD, n=9, 7, 9, 6 | 138.8 Millimeters of mercury (mmHg) | Standard Deviation 12.67 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, pre-dose, n=9, 10, 10, 9 | 137.4 Millimeters of mercury (mmHg) | Standard Deviation 10.71 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 8 hr PD, n=9, 7, 9, 6 | 136.1 Millimeters of mercury (mmHg) | Standard Deviation 13.7 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 83.1 Millimeters of mercury (mmHg) | Standard Deviation 9.97 |
| Cohort 2 UMEC 250 µg in Error | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 24 hr PD, n=9, 7, 9, 6 | 136.0 Millimeters of mercury (mmHg) | Standard Deviation 9.82 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 130.2 Millimeters of mercury (mmHg) | Standard Deviation 10.76 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 1.5 hr PD, n=9, 7, 9, 6 | 81.7 Millimeters of mercury (mmHg) | Standard Deviation 3.5 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, pre-dose, n=9, 7, 9, 6 | 76.5 Millimeters of mercury (mmHg) | Standard Deviation 4.35 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, pre-dose, n=9, 10, 10, 9 | 82.4 Millimeters of mercury (mmHg) | Standard Deviation 5.25 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 8 hr PD, n=9, 9, 10, 9 | 146.2 Millimeters of mercury (mmHg) | Standard Deviation 14.19 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 45 min PD, n=9, 9, 10, 9 | 140.1 Millimeters of mercury (mmHg) | Standard Deviation 17.64 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 15 min PD, n=9, 7, 9, 6 | 127.5 Millimeters of mercury (mmHg) | Standard Deviation 14.29 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 15 min PD, n=9, 9, 10, 8 | 85.8 Millimeters of mercury (mmHg) | Standard Deviation 10.46 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 15 min PD, n=9, 9, 10, 8 | 135.0 Millimeters of mercury (mmHg) | Standard Deviation 14.72 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 24 hr PD, n=9, 7, 9, 6 | 79.8 Millimeters of mercury (mmHg) | Standard Deviation 4.79 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 15 min PD, n=9, 7, 9, 6 | 81.8 Millimeters of mercury (mmHg) | Standard Deviation 5.46 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 45 min PD, n=9, 9, 10, 9 | 83.8 Millimeters of mercury (mmHg) | Standard Deviation 7.9 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 4 hr PD, n=9, 9, 10, 9 | 138.9 Millimeters of mercury (mmHg) | Standard Deviation 11.79 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 24 hr PD, n=9, 7, 9, 6 | 127.5 Millimeters of mercury (mmHg) | Standard Deviation 7.71 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 8 hr PD, n=9, 7, 9, 6 | 77.8 Millimeters of mercury (mmHg) | Standard Deviation 3.54 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 85.4 Millimeters of mercury (mmHg) | Standard Deviation 6.88 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 4 hr PD, n=9, 7, 9, 6 | 135.0 Millimeters of mercury (mmHg) | Standard Deviation 14.6 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 4 hr PD, n=9, 7, 9, 6 | 81.0 Millimeters of mercury (mmHg) | Standard Deviation 4 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 45 min PD, n=9, 7, 9, 6 | 126.3 Millimeters of mercury (mmHg) | Standard Deviation 14.28 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 4 hr PD, n=9, 9, 10, 9 | 83.7 Millimeters of mercury (mmHg) | Standard Deviation 6.06 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, 1.5 hr PD, n=9, 9, 10, 9 | 145.0 Millimeters of mercury (mmHg) | Standard Deviation 21.27 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 1, pre-dose, n=9, 10, 10, 9 | 138.6 Millimeters of mercury (mmHg) | Standard Deviation 19.13 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, 8 hr PD, n=9, 7, 9, 6 | 125.7 Millimeters of mercury (mmHg) | Standard Deviation 8.29 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 1, 8 hr PD, n=9, 9, 10, 9 | 85.3 Millimeters of mercury (mmHg) | Standard Deviation 6.08 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | DBP, Day 7, 45 min PD, n=9, 7, 9, 6 | 81.8 Millimeters of mercury (mmHg) | Standard Deviation 6.49 |
| Cohort 3 UMEC 1000 µg | Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 | SBP, Day 7, pre-dose, n=9, 7, 9, 6 | 120.2 Millimeters of mercury (mmHg) | Standard Deviation 10.97 |
Primary
Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7
Twenty-four hour Holter ECG values were obtained at Screening and on Day 7. During the Screening procedure and study, standard Holter monitors were used (in order to exclude participants with underlying cardiac arrhythmogenicity). During the treatment periods, Holter monitors were only switched on immediately prior to dosing (up to 15 minutes pre-dose) so as to capture Holter ECG data from the 24 hour period following dosing. The following summary data were transcribed into the Case Report Form: Maximum and mean (0 to24 hour) heart rate; normal and aberrant beats and arrhythmias. Analysis of the Holter tapes was arranged by GlaxoSmithKline.The number of participants with normal (NL), abnormal not clinically significant (Abn NCS), and abnormal clinically significant (Abn CS) ECG findings, as well as those with unavailable results (NA) at Screening and Day 7, are reported. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee.
Time frame: Screening and Day 7
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, NL, n=9 ,10, 10, 9 | 2 Participants |
| Placebo | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, Abn NCS, n=9, 7, 9, 6 | 6 Participants |
| Placebo | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, Abn NCS, n=9 ,10, 10, 9 | 7 Participants |
| Placebo | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, NA, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, Abn CS, n=9 ,10, 10, 9 | 0 Participants |
| Placebo | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, NL, n=9, 7, 9, 6 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, NL, n=9, 7, 9, 6 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, Abn CS, n=9 ,10, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, NA, n=9, 7, 9, 6 | 1 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, Abn NCS, n=9 ,10, 10, 9 | 4 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, NL, n=9 ,10, 10, 9 | 6 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, NL, n=9, 7, 9, 6 | 2 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, NL, n=9 ,10, 10, 9 | 5 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, Abn NCS, n=9 ,10, 10, 9 | 4 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, Abn CS, n=9 ,10, 10, 9 | 1 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, Abn NCS, n=9, 7, 9, 6 | 6 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, Abn CS, n=9, 7, 9, 6 | 1 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, Abn CS, n=9 ,10, 10, 9 | 1 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, Abn NCS, n=9 ,10, 10, 9 | 5 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Screening, NL, n=9 ,10, 10, 9 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, Abn NCS, n=9, 7, 9, 6 | 5 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 | Day7, NL, n=9, 7, 9, 6 | 1 Participants |
Primary
Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE)
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An on-treatment adverse event is defined as an event that occurred between the start of investigational product and follow-up contact. Refer to the general SAE/non-serious AE module for a complete list of AEs reported in the study. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect.
Time frame: From start of treatment to study day 12
Population: All Subjects Population: all participants who received at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) | Any on-treatment AE | 6 participants |
| Placebo | Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) | Any on-treatment SAE | 0 participants |
| Cohort 1 UMEC 250 µg | Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) | Any on-treatment SAE | 0 participants |
| Cohort 1 UMEC 250 µg | Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) | Any on-treatment AE | 2 participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) | Any on-treatment AE | 8 participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) | Any on-treatment SAE | 0 participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) | Any on-treatment AE | 5 participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) | Any on-treatment SAE | 0 participants |
Primary
Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7
The number of participants with normal (NL), abnormal not clinically significant (Abn NCS), and abnormal clinically significant (Abn CS) ECG findings, as well as those with unavailable results (NA) at pre-dose (PD1, PD2, PD3), and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose (PD) on Day 1 and at pre-dose (PD1, PD2, PD3), and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr post-dose on Day 7 are reported. The following are of potential clinical importance: absolute QTc interval \>450 milliseconds (msec); increase from Baseline QTc \>60 msec; PR interval \<110 and \>220 msec; QRS interval \<75 and \>110 msec. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee.
Time frame: Day 1 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose) and Day 7 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr)
Population: All Subjects Population. Only participants with data available at the indicated time points were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, NA, n=9, 10, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, NL, n=9, 9, 10, 9 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, NL, n=9, 7, 8, 6 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, NA, n=9, 10, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, NA, n=9, 7, 8, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, Abn NCS, n=9, 9, 10, 9 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, NA, n=9, 7, 8, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, NL, n=9, 7, 9, 6 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, Abn NCS, n=9, 10, 10, 9 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, Abn NCS, n=9, 7, 9, 6 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, Abn NCS, n=9, 7, 9, 6 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, NL, n=9, 9, 10, 9 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, NL, n=9, 7, 9, 6 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, NL, n=9, 10, 10, 9 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, Abn NCS, n=9, 7, 9, 6 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, Abn NCS, n=9, 9, 10, 9 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, Abn CS, 9, 10, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, NL, n=9, 7, 9, 6 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, NL, n=9, 7, 8, 6 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, NL, n=9, 10, 10, 9 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, Abn NCS, n=9, 7, 8, 6 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, NA, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, NA, n=9, 10, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, NL, n=9, 9, 10, 9 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, NL, n=9, 10, 10, 9 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, Abn NCS, n=9, 10, 10, 9 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, Abn NCS, n=9, 9, 10, 9 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, Abn NCS, n=9, 7, 9, 6 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, NL, n=9, 9, 10, 9 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, Abn NCS, n=9, 7, 8, 6 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, Abn CS, n=9, 10, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, Abn NCS, n=9, 7, 9, 6 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, Abn NCS, n=9, 9, 10, 9 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, NL, n=9, 7, 9, 6 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, Abn NCS, n=9, 7, 9, 6 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, NL, n=9, 9, 10, 9 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, Abn CS, n=9, 10, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, Abn NCS, n=9, 10, 10, 9 | 5 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, Abn NCS, n=9, 9, 10, 9 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, NL, n=9, 7, 9, 6 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, Abn CS, 9, 7, 8, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, NL, n=9, 7, 9, 6 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, Abn CS, n=9, 7, 8, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, NL, n=9, 7, 9, 6 | 4 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Placebo | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, Abn NCS, n=9, 7, 9, 6 | 5 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, Abn NCS, n=9, 7, 9, 6 | 5 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, NA, n=9, 10, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, Abn NCS, n=9, 7, 8, 6 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, Abn CS, n=9, 7, 8, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, NL, n=9, 10, 10, 9 | 4 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, NL, n=9, 7, 9, 6 | 4 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, NA, n=9, 7, 8, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, NL, n=9, 7, 8, 6 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, Abn NCS, n=9, 7, 8, 6 | 4 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, Abn CS, 9, 7, 8, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, NL, n=9, 9, 10, 9 | 6 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, NA, n=9, 7, 8, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, Abn NCS, n=9, 10, 10, 9 | 6 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, NL, n=9, 7, 9, 6 | 4 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, Abn NCS, n=9, 10, 10, 9 | 7 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, Abn CS, 9, 10, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, NA, n=9, 10, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, NL, n=9, 9, 10, 9 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, NL, n=9, 7, 9, 6 | 4 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, Abn NCS, n=9, 9, 10, 9 | 6 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, Abn CS, n=9, 10, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, NL, n=9, 9, 10, 9 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, Abn NCS, n=9, 9, 10, 9 | 6 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, NA, n=9, 10, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, NL, n=9, 7, 8, 6 | 4 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, Abn NCS, n=9, 7, 9, 6 | 2 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, NL, n=9, 9, 10, 9 | 6 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, NL, n=9, 7, 9, 6 | 5 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, Abn NCS, n=9, 9, 10, 9 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, NL, n=9, 10, 10, 9 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, NL, n=9, 7, 9, 6 | 2 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, NL, n=9, 9, 10, 9 | 4 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, Abn NCS, n=9, 9, 10, 9 | 5 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, Abn NCS, n=9, 10, 10, 9 | 7 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, NL, n=9, 10, 10, 9 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, NL, n=9, 7, 9, 6 | 4 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, Abn NCS, n=9, 9, 10, 9 | 3 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, Abn CS, n=9, 10, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, NL, n=9, 7, 9, 6 | 4 Participants |
| Cohort 1 UMEC 250 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, Abn CS, 9, 7, 8, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, NL, n=9, 10, 10, 9 | 6 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, Abn NCS, n=9, 10, 10, 9 | 4 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, Abn CS, n=9, 10, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, NA, n=9, 10, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, NL, n=9, 10, 10, 9 | 5 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, Abn NCS, n=9, 10, 10, 9 | 5 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, Abn CS, n=9, 10, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, NA, n=9, 10, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, NL, n=9, 10, 10, 9 | 5 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, Abn NCS, n=9, 10, 10, 9 | 5 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, Abn CS, 9, 10, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, NA, n=9, 10, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, NL, n=9, 9, 10, 9 | 7 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, Abn NCS, n=9, 9, 10, 9 | 3 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, NL, n=9, 9, 10, 9 | 7 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, Abn NCS, n=9, 9, 10, 9 | 3 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, NL, n=9, 9, 10, 9 | 6 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, Abn NCS, n=9, 9, 10, 9 | 4 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, NL, n=9, 9, 10, 9 | 6 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, Abn NCS, n=9, 9, 10, 9 | 4 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, NL, n=9, 9, 10, 9 | 7 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, Abn NCS, n=9, 9, 10, 9 | 3 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, NL, n=9, 7, 9, 6 | 7 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, Abn NCS, n=9, 7, 9, 6 | 2 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, NL, n=9, 7, 8, 6 | 6 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, Abn NCS, n=9, 7, 8, 6 | 2 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, Abn CS, n=9, 7, 8, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, NA, n=9, 7, 8, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, NL, n=9, 7, 8, 6 | 6 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, Abn NCS, n=9, 7, 8, 6 | 2 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, NA, n=9, 7, 8, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, NL, n=9, 7, 9, 6 | 7 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, Abn NCS, n=9, 7, 9, 6 | 2 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, NL, n=9, 7, 9, 6 | 6 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, NL, n=9, 7, 9, 6 | 7 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, Abn NCS, n=9, 7, 9, 6 | 2 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, NL, n=9, 7, 9, 6 | 7 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, Abn NCS, n=9, 7, 9, 6 | 2 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, NL, n=9, 7, 9, 6 | 7 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, Abn NCS, n=9, 7, 9, 6 | 2 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, NL, n=9, 7, 9, 6 | 6 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 2 UMEC 250 µg in Error | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, NL, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, NL, n=9, 9, 10, 9 | 6 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, Abn NCS, n=9, 10, 10, 9 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, NL, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, NL, n=9, 10, 10, 9 | 5 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, Abn NCS, n=9, 9, 10, 9 | 4 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 4 hr PD, NL, n=9, 9, 10, 9 | 5 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, NL, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 1.5 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, Abn NCS, n=9, 9, 10, 9 | 4 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 1.5 hr PD, NL, n=9, 9, 10, 9 | 5 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, NA, n=9, 10, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, NL, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, Abn CS, n=9, 10, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, Abn NCS, n=9, 9, 10, 9 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 45 min PD, NL, n=9, 9, 10, 9 | 6 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 8 hr PD, Abn NCS, n=9, 9, 10, 9 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, NA, n=9, 9, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, Abn CS, n=9, 9, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 4 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, Abn NCS, n=9, 9, 10, 9 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, 15 min PD, NL, n=9, 9, 10, 9 | 6 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, Abn NCS, n=9, 10, 10, 9 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, NL, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, NA, n=9, 10, 10, 9 | 1 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, Abn CS, 9, 10, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD1, NL, n=9, 10, 10, 9 | 6 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, Abn NCS, n=9, 10, 10, 9 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, NL, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD3, NL, n=9, 10, 10, 9 | 5 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, NA, n=9, 7, 8, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, Abn CS, 9, 7, 8, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, Abn NCS, n=9, 7, 8, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD3, NL, n=9, 7, 8, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 8 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 15 min PD, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, NA, n=9, 7, 8, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, Abn CS, n=9, 7, 8, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, NA, n=9, 10, 10, 9 | 1 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, NL, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, Abn NCS, n=9, 7, 8, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD2, NL, n=9, 7, 8, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 1, PD2, Abn CS, n=9, 10, 10, 9 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, NA, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, PD1, Abn NCS, n=9, 7, 9, 6 | 3 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 24 hr PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
| Cohort 3 UMEC 1000 µg | Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 | Day 7, 45 min PD, Abn CS, n=9, 7, 9, 6 | 0 Participants |
Primary
Total Number of Salbutamol Doses Taken Over the 7 -Day Study Period
The total number of salbutamol doses taken per day was recorded by the participants in their dairy card over the entire 7-day treatment period. Diaries were reviewed by the Investigator when participants were admitted to the unit on Day 1, Day 7, and Day 8. Salbutamol was given as rescue medication, defined as a quick-relief or fast-acting medication that is given in addition to the investigational drug or placebo that can alleviate symptoms due to disease or lack of efficacy of the study treatment.
Time frame: Day 1 to Day 7
Population: All Subjects Population. Only those participants who took at least one dose of salbutamol were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Total Number of Salbutamol Doses Taken Over the 7 -Day Study Period | 18 salbutamol doses |
| Cohort 1 UMEC 250 µg | Total Number of Salbutamol Doses Taken Over the 7 -Day Study Period | 33 salbutamol doses |
| Cohort 2 UMEC 250 µg in Error | Total Number of Salbutamol Doses Taken Over the 7 -Day Study Period | 33 salbutamol doses |
| Cohort 3 UMEC 1000 µg | Total Number of Salbutamol Doses Taken Over the 7 -Day Study Period | 29 salbutamol doses |
Secondary
Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7
Urinary recovery of unchanged drug (UMEC) within the first 8, 12, and 24 hours (Ae\[0-8\], Ae\[0-12\], and Ae\[0-24\], respectively) on Day 1 and within the first 4, 8, 12, and 24 hours (Ae\[0-4\], Ae\[0-8\], Ae\[0-12\], and Ae\[0-24\], respectively) on Day 7 was estimated. Urine samples were collected from 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1 and from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7.
Time frame: From 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1; from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7
Population: PK Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 UMEC 250 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-12), Day 1, n=0, 6, 7, 8 | 2022.3 nanograms (ng) | Geometric Coefficient of Variation 41.2 |
| Cohort 1 UMEC 250 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-4), Day 7, n=0, 5, 8, 6 | 1223.6 nanograms (ng) | Geometric Coefficient of Variation 77.8 |
| Cohort 1 UMEC 250 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-24), Day 1, n=0, 6, 7, 8 | 2503.5 nanograms (ng) | Geometric Coefficient of Variation 38 |
| Cohort 1 UMEC 250 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-12), Day 7, n=0, 5, 8, 6 | 4165.6 nanograms (ng) | Geometric Coefficient of Variation 15.3 |
| Cohort 1 UMEC 250 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-8), Day 7, n=0, 5, 8, 6 | 3115.8 nanograms (ng) | Geometric Coefficient of Variation 27.2 |
| Cohort 1 UMEC 250 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-8), Day 1, n=0, 6, 7, 8 | 1756.0 nanograms (ng) | Geometric Coefficient of Variation 46.6 |
| Cohort 1 UMEC 250 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-24), Day 7, n=0, 5, 8, 6 | 5606.2 nanograms (ng) | Geometric Coefficient of Variation 15.3 |
| Cohort 2 UMEC 250 µg in Error | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-4), Day 7, n=0, 5, 8, 6 | 669.5 nanograms (ng) | Geometric Coefficient of Variation 129.8 |
| Cohort 2 UMEC 250 µg in Error | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-8), Day 1, n=0, 6, 7, 8 | 755.9 nanograms (ng) | Geometric Coefficient of Variation 101.5 |
| Cohort 2 UMEC 250 µg in Error | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-8), Day 7, n=0, 5, 8, 6 | 1430.8 nanograms (ng) | Geometric Coefficient of Variation 49.6 |
| Cohort 2 UMEC 250 µg in Error | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-12), Day 1, n=0, 6, 7, 8 | 921.7 nanograms (ng) | Geometric Coefficient of Variation 97.6 |
| Cohort 2 UMEC 250 µg in Error | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-12), Day 7, n=0, 5, 8, 6 | 1960.5 nanograms (ng) | Geometric Coefficient of Variation 53.6 |
| Cohort 2 UMEC 250 µg in Error | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-24), Day 1, n=0, 6, 7, 8 | 1420.3 nanograms (ng) | Geometric Coefficient of Variation 130.9 |
| Cohort 2 UMEC 250 µg in Error | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-24), Day 7, n=0, 5, 8, 6 | 2984.5 nanograms (ng) | Geometric Coefficient of Variation 52.9 |
| Cohort 3 UMEC 1000 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-8), Day 1, n=0, 6, 7, 8 | 13435.9 nanograms (ng) | Geometric Coefficient of Variation 53.8 |
| Cohort 3 UMEC 1000 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-24), Day 1, n=0, 6, 7, 8 | 19552.7 nanograms (ng) | Geometric Coefficient of Variation 47.4 |
| Cohort 3 UMEC 1000 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-8), Day 7, n=0, 5, 8, 6 | 19319.3 nanograms (ng) | Geometric Coefficient of Variation 50.5 |
| Cohort 3 UMEC 1000 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-4), Day 7, n=0, 5, 8, 6 | 11854.5 nanograms (ng) | Geometric Coefficient of Variation 65.8 |
| Cohort 3 UMEC 1000 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-24), Day 7, n=0, 5, 8, 6 | 32140.0 nanograms (ng) | Geometric Coefficient of Variation 36.2 |
| Cohort 3 UMEC 1000 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-12), Day 7, n=0, 5, 8, 6 | 23496.1 nanograms (ng) | Geometric Coefficient of Variation 44.7 |
| Cohort 3 UMEC 1000 µg | Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 | Ae(0-12), Day 1, n=0, 6, 7, 8 | 16069.2 nanograms (ng) | Geometric Coefficient of Variation 56 |
Secondary
Cmax of UMEC on Day 1 and Day 7
Cmax is defined as the maximum observed concentration of UMEC and was measured on Day 1 and Day 7. Blood samples were collected pre-dose and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose on Day 1 and Day 7. Also, a 24 hr blood sample was collected on Day 7.
Time frame: Day 1 and Day 7: pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose; 24 hr post-dose on Day 7
Population: PK Population. Only participants with data available at the indicated time points were summarized.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 UMEC 250 µg | Cmax of UMEC on Day 1 and Day 7 | Day 1, n=0, 8, 9, 9 | 0.21654 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| Cohort 1 UMEC 250 µg | Cmax of UMEC on Day 1 and Day 7 | Day 7, n=0, 6, 8, 6 | 0.33206 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 58.3 |
| Cohort 2 UMEC 250 µg in Error | Cmax of UMEC on Day 1 and Day 7 | Day 1, n=0, 8, 9, 9 | 0.07915 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 147.6 |
| Cohort 2 UMEC 250 µg in Error | Cmax of UMEC on Day 1 and Day 7 | Day 7, n=0, 6, 8, 6 | 0.16448 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74.2 |
| Cohort 3 UMEC 1000 µg | Cmax of UMEC on Day 1 and Day 7 | Day 1, n=0, 8, 9, 9 | 1.52835 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 53.6 |
| Cohort 3 UMEC 1000 µg | Cmax of UMEC on Day 1 and Day 7 | Day 7, n=0, 6, 8, 6 | 2.75864 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 60.5 |
Secondary
Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7
The fraction of the total dose excreted (Fe) in each interval was estimated as the urinary recovery of unchanged drug (Ae) per dose. Urine samples were collected from 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1 and from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7.
Time frame: From 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1; from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7
Population: PK Population: Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the PK Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 UMEC 250 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-8), Day 1, n=0, 6, 8, 8 | 0.76 Percentage of dose administered | Standard Deviation 0.35 |
| Cohort 1 UMEC 250 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-12), Day 7, n=0, 5, 8, 6 | 1.68 Percentage of dose administered | Standard Deviation 0.25 |
| Cohort 1 UMEC 250 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-12), Day 1, n=0, 6, 8, 8 | 0.87 Percentage of dose administered | Standard Deviation 0.38 |
| Cohort 1 UMEC 250 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-4), Day 7, n=0, 5, 8, 6 | 0.58 Percentage of dose administered | Standard Deviation 0.35 |
| Cohort 1 UMEC 250 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-24), Day 7, n=0, 5, 8, 6 | 2.26 Percentage of dose administered | Standard Deviation 0.33 |
| Cohort 1 UMEC 250 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-24), Day 1, n=0, 6, 8, 8 | 1.06 Percentage of dose administered | Standard Deviation 0.41 |
| Cohort 1 UMEC 250 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-8), Day 7, n=0, 5, 8, 6 | 1.28 Percentage of dose administered | Standard Deviation 0.3 |
| Cohort 2 UMEC 250 µg in Error | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-12), Day 1, n=0, 6, 8, 8 | 0.41 Percentage of dose administered | Standard Deviation 0.32 |
| Cohort 2 UMEC 250 µg in Error | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-4), Day 7, n=0, 5, 8, 6 | 0.37 Percentage of dose administered | Standard Deviation 0.3 |
| Cohort 2 UMEC 250 µg in Error | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-8), Day 1, n=0, 6, 8, 8 | 0.34 Percentage of dose administered | Standard Deviation 0.28 |
| Cohort 2 UMEC 250 µg in Error | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-8), Day 7, n=0, 5, 8, 6 | 0.62 Percentage of dose administered | Standard Deviation 0.26 |
| Cohort 2 UMEC 250 µg in Error | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-12), Day 7, n=0, 5, 8, 6 | 0.86 Percentage of dose administered | Standard Deviation 0.36 |
| Cohort 2 UMEC 250 µg in Error | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-24), Day 1, n=0, 6, 8, 8 | 0.70 Percentage of dose administered | Standard Deviation 0.61 |
| Cohort 2 UMEC 250 µg in Error | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-24), Day 7, n=0, 5, 8, 6 | 1.31 Percentage of dose administered | Standard Deviation 0.54 |
| Cohort 3 UMEC 1000 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-12), Day 7, n=0, 5, 8, 6 | 2.52 Percentage of dose administered | Standard Deviation 0.99 |
| Cohort 3 UMEC 1000 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-8), Day 1, n=0, 6, 8, 8 | 1.49 Percentage of dose administered | Standard Deviation 0.68 |
| Cohort 3 UMEC 1000 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-24), Day 7, n=0, 5, 8, 6 | 3.38 Percentage of dose administered | Standard Deviation 1.15 |
| Cohort 3 UMEC 1000 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-24), Day 1, n=0, 6, 8, 8 | 2.12 Percentage of dose administered | Standard Deviation 0.82 |
| Cohort 3 UMEC 1000 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-12), Day 1, n=0, 6, 8, 8 | 1.78 Percentage of dose administered | Standard Deviation 0.77 |
| Cohort 3 UMEC 1000 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-8), Day 7, n=0, 5, 8, 6 | 2.10 Percentage of dose administered | Standard Deviation 0.84 |
| Cohort 3 UMEC 1000 µg | Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 | Fe(0-4), Day 7, n=0, 5, 8, 6 | 1.35 Percentage of dose administered | Standard Deviation 0.7 |
Secondary
Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7
Area under the concentration-time (AUC) curve from time zero (pre-dose) to 2 hours (AUC\[0-2\]), from time zero to 8 hours (AUC\[0-8\]), from time zero to the last time of a quantifiable concentration of UMEC (AUC\[0-t\]) on Day 1 and Day 7 were measured. AUC is a measure of systemic exposure. Blood samples were collected pre-dose and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose on Day 1 and Day 7. Also, a 24 hr blood sample was collected on Day 7.
Time frame: Day 1 and Day 7: pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose; 24 hr post-dose on Day 7
Population: Pharmacokinetic (PK) Population: participants (par.) in the ASP for whom a PK sample was obtained and analyzed. Different par. may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of par. summarized reflects everyone in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 UMEC 250 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-t), Day 1, n=0, 8, 9, 9 | 0.26071 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 39.1 |
| Cohort 1 UMEC 250 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-8), Day 1, n=0, 0, 0, 9 | NA hr * nanograms per milliliter (ng/mL) | — |
| Cohort 1 UMEC 250 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-8), Day 7, n=0, 0, 0, 6 | NA hr * nanograms per milliliter (ng/mL) | — |
| Cohort 1 UMEC 250 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-t), Day 7, n=0, 6, 8, 6 | 0.55514 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 113.2 |
| Cohort 1 UMEC 250 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-2), Day 7, n=0, 6, 8, 6 | 0.31951 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51.6 |
| Cohort 1 UMEC 250 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-2), Day 1, n=0, 8, 9, 9 | 0.19675 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19.7 |
| Cohort 2 UMEC 250 µg in Error | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-8), Day 1, n=0, 0, 0, 9 | NA hr * nanograms per milliliter (ng/mL) | — |
| Cohort 2 UMEC 250 µg in Error | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-2), Day 1, n=0, 8, 9, 9 | 0.08134 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 108 |
| Cohort 2 UMEC 250 µg in Error | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-2), Day 7, n=0, 6, 8, 6 | 0.15527 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 66.5 |
| Cohort 2 UMEC 250 µg in Error | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-8), Day 7, n=0, 0, 0, 6 | NA hr * nanograms per milliliter (ng/mL) | — |
| Cohort 2 UMEC 250 µg in Error | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-t), Day 1, n=0, 8, 9, 9 | 0.03614 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 1707.8 |
| Cohort 2 UMEC 250 µg in Error | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-t), Day 7, n=0, 6, 8, 6 | 0.30526 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 134.3 |
| Cohort 3 UMEC 1000 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-2), Day 7, n=0, 6, 8, 6 | 1.92508 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.1 |
| Cohort 3 UMEC 1000 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-t), Day 7, n=0, 6, 8, 6 | 4.86204 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 42.8 |
| Cohort 3 UMEC 1000 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-t), Day 1, n=0, 8, 9, 9 | 0.93299 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 5820.5 |
| Cohort 3 UMEC 1000 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-8), Day 1, n=0, 0, 0, 9 | 2.029 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 69.8 |
| Cohort 3 UMEC 1000 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-2), Day 1, n=0, 8, 9, 9 | 0.95719 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 233.2 |
| Cohort 3 UMEC 1000 µg | Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 | AUC(0-8), Day 7, n=0, 0, 0, 6 | 3.320 hr * nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33.3 |
Secondary
Renal Clearance of UMEC on Day 1 and Day 7
Renal clearance was calculated as the urinary recovery of unchanged drug from time zero to time x (Ae\[0-x\])/area under concentration from time zero to time x (AUC\[0-x\]) for the longest period of time after dosing when both could be accurately determined (where x is either 8, 12, or 24). Urine samples were collected from 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1 and from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7.
Time frame: From 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1; from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7
Population: PK Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 UMEC 250 µg | Renal Clearance of UMEC on Day 1 and Day 7 | Day 1, n=0, 1, 0, 8 | 6.5229 Liters/hour (L/hr) | — |
| Cohort 1 UMEC 250 µg | Renal Clearance of UMEC on Day 1 and Day 7 | Day 7, n=0, 4, 6, 6 | 2.5923 Liters/hour (L/hr) | Geometric Coefficient of Variation 103.6 |
| Cohort 2 UMEC 250 µg in Error | Renal Clearance of UMEC on Day 1 and Day 7 | Day 1, n=0, 1, 0, 8 | NA Liters/hour (L/hr) | — |
| Cohort 2 UMEC 250 µg in Error | Renal Clearance of UMEC on Day 1 and Day 7 | Day 7, n=0, 4, 6, 6 | 4.0826 Liters/hour (L/hr) | Geometric Coefficient of Variation 19.3 |
| Cohort 3 UMEC 1000 µg | Renal Clearance of UMEC on Day 1 and Day 7 | Day 1, n=0, 1, 0, 8 | 5.6173 Liters/hour (L/hr) | Geometric Coefficient of Variation 39.5 |
| Cohort 3 UMEC 1000 µg | Renal Clearance of UMEC on Day 1 and Day 7 | Day 7, n=0, 4, 6, 6 | 6.6104 Liters/hour (L/hr) | Geometric Coefficient of Variation 33.1 |
Secondary
Tmax and Tlastof UMEC on Day 1 and Day 7
Tmax is defined as the time to reach the observed maximum concentration, and tlast is defined as the time of the last quantifiable concentration of UMEC; both were measured on Day 1 and Day 7. Blood samples were collected pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose on Day 1 and Day 7. Also, a 24 hr blood sample was collected on Day 7.
Time frame: Day 1 and Day 7: pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose; 24 hr post-dose on Day 7
Population: PK Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the PK Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 UMEC 250 µg | Tmax and Tlastof UMEC on Day 1 and Day 7 | tlast, Day 1, n=0, 8, 8, 9 | 4.000 hours |
| Cohort 1 UMEC 250 µg | Tmax and Tlastof UMEC on Day 1 and Day 7 | tmax, Day 1, n=0, 8, 8, 9 | 0.080 hours |
| Cohort 1 UMEC 250 µg | Tmax and Tlastof UMEC on Day 1 and Day 7 | tlast, Day 7, n=0, 6, 8, 6 | 6.000 hours |
| Cohort 1 UMEC 250 µg | Tmax and Tlastof UMEC on Day 1 and Day 7 | tmax, Day 7, n=0, 6, 8, 6 | 0.080 hours |
| Cohort 2 UMEC 250 µg in Error | Tmax and Tlastof UMEC on Day 1 and Day 7 | tlast, Day 1, n=0, 8, 8, 9 | 2.000 hours |
| Cohort 2 UMEC 250 µg in Error | Tmax and Tlastof UMEC on Day 1 and Day 7 | tmax, Day 7, n=0, 6, 8, 6 | 0.165 hours |
| Cohort 2 UMEC 250 µg in Error | Tmax and Tlastof UMEC on Day 1 and Day 7 | tmax, Day 1, n=0, 8, 8, 9 | 0.250 hours |
| Cohort 2 UMEC 250 µg in Error | Tmax and Tlastof UMEC on Day 1 and Day 7 | tlast, Day 7, n=0, 6, 8, 6 | 6.015 hours |
| Cohort 3 UMEC 1000 µg | Tmax and Tlastof UMEC on Day 1 and Day 7 | tmax, Day 7, n=0, 6, 8, 6 | 0.240 hours |
| Cohort 3 UMEC 1000 µg | Tmax and Tlastof UMEC on Day 1 and Day 7 | tmax, Day 1, n=0, 8, 8, 9 | 0.250 hours |
| Cohort 3 UMEC 1000 µg | Tmax and Tlastof UMEC on Day 1 and Day 7 | tlast, Day 7, n=0, 6, 8, 6 | 24.010 hours |
| Cohort 3 UMEC 1000 µg | Tmax and Tlastof UMEC on Day 1 and Day 7 | tlast, Day 1, n=0, 8, 8, 9 | 8.000 hours |
Secondary
Urine Half Life (t1/2) of UMEC on Day 7
Urine half life (t1/2) of UMEC on Day 7 was estimated. Urine samples were collected from 0-4 hours (hr), 4-8 hr, 8-12 hr, and 12-24 hr on Day 7.
Time frame: From 0-4 hours (hr), 4-8 hr, 8-12 hr, and 12-24 hr on Day 7
Population: PK Population. Only participants with data available at the indicated time points were summarized.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 UMEC 250 µg | Urine Half Life (t1/2) of UMEC on Day 7 | 5.785 hours | Geometric Coefficient of Variation 39.4 |
| Cohort 2 UMEC 250 µg in Error | Urine Half Life (t1/2) of UMEC on Day 7 | 8.299 hours | Geometric Coefficient of Variation 37.3 |
| Cohort 3 UMEC 1000 µg | Urine Half Life (t1/2) of UMEC on Day 7 | 7.643 hours | Geometric Coefficient of Variation 33.4 |