Asthma
Conditions
Keywords
repeat dose, GSK2292767, smoke, tolerability, safety, dry powder inhalation, pharmacokinetics, single dose
Brief summary
This study is the first administration of GSK2292767 to humans. The study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and repeat inhaled doses of GSK2292767 in healthy smokers. This study is intended to provide sufficient confidence in the safety of the molecule and preliminary information on target engagement to allow progression to further repeat dose and proof of mechanism studies. This is a two part, single site, randomized, double-blind (sponsor open), placebo controlled study. Part A will consist of two 3-period interlocking cohorts to evaluate the safety, tolerability and pharmacokinetics of ascending single doses of GSK2292767 administered as a dry powder inhalation. Part B is planned to follow Part A and progression will be based on an acceptable safety, tolerability and pharmacokinetic profiles. Subjects will receive repeat doses of GSK2292767 once daily for 14 days during Part B.
Interventions
DRUGGSK2292767 50 μg
GSK2292767 50 μg blended with lactose and magnesium stearate per blister as powder for inhalation
DRUGGSK2292767 500 μg
GSK2292767 500 μg blended with lactose and magnesium stearate per blister as powder for inhalation
DRUGPlacebo
Lactose as powder for inhalation
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent * Participants who are overtly healthy as determined by medical evaluation including (medical history, physical examination, laboratory tests, and cardiac monitoring). A participant with a clinical abnormality or laboratory parameters outside the reference range expected for them and the population being studied may be included only if the Investigator believes that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or outcomes * Participants who are current daily cigarette smokers (manufactured and self-rolled). Must have smoked regularly in the 12-month period preceding the screening visit * Normal spirometry (FEV1 \>=80% of predicted) at screening * Body weight \>=50 kilograms (kg) and body mass index (BMI) within the range 18 to 31 kg/square meter (m\^2) (inclusive) * Male and female * Male participants: A male participant must agree to use contraception as detailed in the protocol during the treatment period and for at least from the time of first dose of study medication until at least 55 (5x11) hours plus an additional 90 days after the last dose of study medication and refrain from donating sperm during this period. GSK2292767 has a predicted half-life of approximately 11 hours * Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP) * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
Exclusion criteria
* History or presence of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data * Abnormal blood pressure as determined by the investigator * Alanine transaminase (ALT) \>1.5xupper limit of normal (ULN) * Bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) * Average corrected QT interval by Fridericia's formula (QTcF) \>450 milliseconds (msec) (based on triplicate ECGs) * Participants who have asthma or a history of asthma (except in childhood and which has now remitted) * Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing. Specific concomitant medications listed in protocol may be allowed * Live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the study * Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within 56 days * Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day * Current enrolment or past participation within the last 90 days of exposure to any other clinical study involving an investigational study treatment or any other type of medical research * Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening * Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment * Positive pre-study drug/alcohol screen * Positive human immunodeficiency virus (HIV) antibody test * Regular use of known drugs of abuse * Regular alcohol consumption within 3 months prior to the study defined as: An average weekly intake of \>14 units for males and females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits * Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study * Participants who are unable to produce a total weight of at least 100 milligrams (mg) of selected sputum during sputum induction at screening * Participants whose primary consumption of tobacco is via methods other than cigarettes (manufactured or self-rolled). Primary methods of tobacco consumption that are excluded include, but are not limited to pipes and cigars
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Number of Participants With Hematology Values of PCC | Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14 | Number of participants with hematology parameters of PCC which shifted from normal to high in part B are presented. Hematology parameters for which PCC values were identified were: Hemoglobin, Hematocrit, Lymphocytes, Total Neutrophils, Platelet count and WBC count |
| Part B: Change From Baseline in Respiratory Rate | Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14 | Respiratory rate in part B was assessed in a semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value. |
| Part A: Change From Baseline in Tympanic Temperature | Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period | Tympanic temperature in part A was assessed in semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value. |
| Part B: Change From Baseline in Tympanic Temperature | Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14 | Tympanic temperature in part B was assessed in semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value. |
| Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 1 (pre-dose and 1 hour) | 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 using spirometry at the indicated time. FEV1 measurements were repeated until three technically acceptable measurements (within 150 milliliter \[mL\] of each other) were made. Data for FEV1 for part A is presented here. |
| Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Up to Day 14 | 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 using spirometry at the indicated time. Existing spirometry equipment was used. FEV1 measurements were repeated until three technically acceptable measurements (within 150 mL of each other) were made. Data for FEV1 for part B is presented here. |
| Part A: Forced Vital Capacity (FVC) | Day 1 (pre-dose and 1 hour) | FVC is a measure of lung function and is defined as total amount of air that can be exhaled during FEV1 test. FVC was planned to measured using spirometry. The FVC need to be normal at screening and is part of the Forced Expiratory ratio (FEV1/FVC) which should lie between 0.7-0.8 to indicate no chronic obstruction or restriction. The FVC was therefore only used at screening and requires no ongoing analysis during the study. All other indications of obstruction in the study, e.g. paradoxical bronchospasm was provided by the FEV1. The FVC therefore require no analysis. |
| Part B: Forced Vital Capacity (FVC) | Day 1 (pre-dose and 1 hour) | FVC is a measure of lung function and is defined as total amount of air that can be exhaled during FEV1 test. FVC was planned to measured using spirometry. The FVC need to be normal at screening and is part of the Forced Expiratory ratio (FEV1/FVC) which should lie between 0.7-0.8 to indicate no chronic obstruction or restriction. The FVC was therefore only used at screening and requires no ongoing analysis during the study. All other indications of obstruction in the study, e.g. paradoxical bronchospasm was provided by the FEV1. The FVC therefore require no analysis. |
| Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Day 1 of each treatment period | Triplicate/Single 12-lead ECG was obtained using an automated ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTFc intervals. Number of participants with abnormal clinically significant and abnormal-not clinically significant values at any time post-Baseline is presented. |
| Part B: Number of Participants With ECG Abnormalities | Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14 | Triplicate/Single 12-lead ECG was obtained using an automated ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTFc intervals. Number of participants with abnormal clinically significant and abnormal-not clinically significant values at any time post-Baseline is presented. |
| Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | 24 hours post-dose in each treatment period. | Number of participants with clinical chemistry values that changed from normal to high or low in part A are presented. Chemistry parameters for which PCC values were identified were: Alkaline Phosphatase, Alanine Amino Transferase, aspartate aminotransferase, Total Bilirubin, calcium, glucose, potassium and Sodium. |
| Part B: Number of Participants With Clinical Chemistry Values of PCC | Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14 | Number of participants with clinical chemistry values that changed from normal to high or low in part B are presented. Chemistry parameters for which PCC values were identified were: Alkaline Phosphatase, Alanine Amino Transferase, aspartate aminotransferase, Total Bilirubin, calcium, glucose, potassium and Sodium. Only participants with data available at specified time points were analyzed (represented by n=X in category titles) |
| Part A: Number of Participants With Hematology Values of PCC | 24 hours post-dose in each treatment period | Number of participants with hematology parameters of PCC which shifted from normal to high in part A are presented. Hematology parameters for which PCC values were identified were: Hemoglobin, Hematocrit, Lymphocytes, Total Neutrophils, Platelet count and White Blood Cell (WBC) Count. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles) |
| Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | Up to 12 weeks | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants with 5 percent nSAEs and SAEs has been reported. |
| Part B: Number of Participants With Any AE and Any SAE | Up to 4 weeks | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants with 5 percent nSAEs and SAEs has been reported. |
| Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period | Blood pressure in part A was assessed in a semi supine position with a completely automated device. SBP and DBP measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment. Change from Baseline was defined as the value at indicated time point minus Baseline value. |
| Part B: Change From Baseline in SBP and DBP | Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14 | Blood pressure in part B were assessed in semi supine position with a completely automated device. SBP and DBP preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. |
| Part A: Change From Baseline in Heart Rate | Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period | Heart rate in part A was assessed in a semi supine position with a completely automated device. Heart rate measurement was preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value. |
| Part B: Change From Baseline in Heart Rate | Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14 | Heart rate in part B was assessed in a semi supine position with a completely automated device. Heart rate measurement was preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value. |
| Part A: Change From Baseline in Respiratory Rate | Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period | Respiratory rate in part A was assessed in a semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | Pre-dose (5 minutes (min), 30 min, 45 min, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods | Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for AUC (0 to t), AUC (0 to 24) and AUC (0 to inf) of GSK2292767 for part A is presented. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). Pharmacokinetic population comprised of participants in the 'All participant' population for whom a pharmacokinetic sample was obtained and analyzed. |
| Part B: AUC (0 to t), AUC (0 to 24) and AUC (0 to Inf) of GSK2292767 | Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14 | Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for AUC (0 to t), AUC (0 to 24) and AUC (0 to inf) of GSK2292767 for part B is presented. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). |
| Part A: Maximum Observed Plasma Drug Concentration (Cmax) of GSK2292767 | Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods | Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Five min post dose concentrations on Days 2-13 were assumed to be the Cmax values. Data for Cmax of GSK2292767 for part A is presented. Cmax is defined as maximum observed plasma concentration of GSK2292767. |
| Part B: Cmax of GSK2292767 | Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14 | Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Five minute post dose concentrations on Days 2-13 were assumed to be the Cmax values. Data for Cmax of GSK2292767 for part B is presented. |
| Part A: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK2292767 | Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods | Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Tmax of GSK2292767 for part A is presented. |
| Part B: Tmax of GSK2292767 | Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14 | Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Tmax of GSK2292767 for part B is presented. |
| Part A: Terminal Half-life (T1/2) of GSK2292767 | Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods | Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for T1/2 of GSK2292767 for part A is presented. T1/2 is defined as the time required for one half of the total amount of a particular substance in a biological system to be degraded by biological processes. Only those participants with data available at the specified time points were analyzed. |
| Part B: T1/2 of GSK2292767 | Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14 | Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for T1/2 of GSK2292767 for part B is presented. T1/2 was defined as the time required for one half of the total amount of a particular substance in a biological system to be degraded by biological processes. Only those participants with data available at the specified time points were analyzed. |
| Part A: Trough Concentrations (Ctau) of GSK2292767 | 24 hr post dose in each of the 3 treatment periods | Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Ctau of GSK2292767 for part A is presented. Ctau is defined as the lowest concentration reached by a drug before the next dose is administered. |
| Part B: Ctau of GSK2292767 | Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14 | Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Ctau of GSK2292767 for part B is presented. Ctau is defined as the lowest concentration reached by a drug before the next dose is administered. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). |
| Part B: Concentration of GSK2292767 in Lung Epithelial Lining Fluid (ELF) | Day 15 | ELF from the lung was extracted from BAL samples. ELF drug concentration was calculated as BAL fluid drug concentration multiplied by dilution factor where dilution factor = Plasma urea (pre-bronchoscopy) divided by BAL urea. NA indicates data not available. Only participants with data available at specified time points were analyzed (represented by n=X in category titles). |
| Part B: Concentration of GSK2292767 in Bronchoalveolar Lavage (BAL) | Day 15 | BAL samples were collected by bronchoscopy. |
Countries
United Kingdom
Participant flow
Recruitment details
This is a two part, single site, randomized, double-blind (sponsor open), placebo controlled study in healthy smokers. Study was conducted in the United Kingdom.
Pre-assignment details
Part A comprised of two cohorts, each of which consisted of 3 treatment periods with 4 treatment sequences. Out of 98 screened participants, 37 were randomized, 58 were screen failures and 3 were retained as reserve participants. In Part B, 12 participants were included, 11 of them were taken from Part A and 1 additional participant only for Part B
Participants by arm
| Arm | Count |
|---|---|
| Part A:Placebo/200 µg GSK2292767/1000 µg GSK2292767 Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 1 were administered a single dose of placebo in Period 1, 200 µg GSK2292767 in Period 2 and 1000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA Dry Powder Inhaler (DPI). There was a period of 4 weeks between doses for an individual participant. | 7 |
| Part A:50 µg GSK2292767/Placebo/1000 µg GSK2292767 Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 2 were administered a single dose of 50 µg GSK2292767 in Period 1, placebo in Period 2 and 1000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. | 3 |
| Part A:50 µg GSK2292767/200 µg GSK2292767/Placebo Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 3 were administered a single dose of 50 µg GSK2292767 in Period 1, 200 µg GSK2292767 in Period 2 and placebo in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. | 5 |
| Part A:50 µg GSK2292767/200 µg GSK2292767/1000 µg GSK2292767 Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 4 were administered a single dose of 50 µg GSK2292767 in Period 1, 200 µg GSK2292767 in Period 2 and 1000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. | 6 |
| Part A:Placebo/500 µg GSK2292767/2000 µg GSK2292767 Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 5 were administered a single dose of placebo in Period 1, 500 µg GSK2292767 in Period 2 and 2000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. | 4 |
| Part A:100 µg GSK2292767/Placebo/2000 µg GSK2292767 Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 6 were administered a single dose of 100 ug GSK2292767 in Period 1, placebo in Period 2 and 2000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. | 4 |
| Part A:100 µg GSK2292767/500 µg GSK2292767/Placebo Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 7 were administered a single dose of 100 µg GSK2292767 in Period 1, 500 µg GSK2292767 in Period 2 and placebo in Period 3. The treatment was administered via ELLIPTA DPI. There was a period of 4 weeks between doses for an individual participant. | 4 |
| Part A:100 µg GSK2292767/500 µg GSK2292767/2000 µg GSK2292767 Part A consisted of two cohorts each containing three treatment periods with four treatment sequences. Participants randomized to Sequence 8 were administered a single dose of 100 µg GSK2292767 in Period 1, 500 µg GSK2292767 in Period 2 and 2000 µg GSK2292767 in Period 3. The treatment was administered via ELLIPTA DPI . There was a period of 4 weeks between doses for an individual participant. | 4 |
| Part B: Placebo Participants were administered once daily dose of placebo for 14 days via inhalation route using ELLIPTA DPI | 3 |
| Part B: GSK2292767 2000 µg OD Participants were administered 2000 µg GSK2292767 once daily for 14 days via inhalation route using ELLIPTA DPI | 9 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A, Period 2 (1 Day) | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A,Washout Period 1(4 Weeks) | Physician Decision | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A,Washout Period 1(4 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A,Washout Period 2 (4 Weeks) | Physician Decision | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A,Washout Period 2 (4 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A:Placebo/200 µg GSK2292767/1000 µg GSK2292767 | Part A:50 µg GSK2292767/Placebo/1000 µg GSK2292767 | Part A:50 µg GSK2292767/200 µg GSK2292767/Placebo | Part A:50 µg GSK2292767/200 µg GSK2292767/1000 µg GSK2292767 | Part A:Placebo/500 µg GSK2292767/2000 µg GSK2292767 | Part A:100 µg GSK2292767/Placebo/2000 µg GSK2292767 | Part A:100 µg GSK2292767/500 µg GSK2292767/Placebo | Part A:100 µg GSK2292767/500 µg GSK2292767/2000 µg GSK2292767 | Part B: Placebo | Part B: GSK2292767 2000 µg OD | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 2 Participants | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 9 Participants | 48 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 3 Participants | 4 Participants | 6 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 9 Participants | 46 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 9 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 12 | 0 / 9 | 0 / 12 | 0 / 3 | 0 / 9 |
| other Total, other adverse events | 6 / 23 | 9 / 12 | 6 / 12 | 7 / 13 | 6 / 12 | 4 / 9 | 5 / 12 | 3 / 3 | 8 / 9 |
| serious Total, serious adverse events | 0 / 23 | 0 / 12 | 0 / 12 | 0 / 13 | 0 / 12 | 0 / 9 | 0 / 12 | 0 / 3 | 0 / 9 |
Outcome results
Primary
Part A: Change From Baseline in Heart Rate
Heart rate in part A was assessed in a semi supine position with a completely automated device. Heart rate measurement was preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Time frame: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part A: Change From Baseline in Heart Rate | 12 hour | 4.2 Beats per minute | Standard Deviation 7.11 |
| Placebo | Part A: Change From Baseline in Heart Rate | 6 hour | 4.3 Beats per minute | Standard Deviation 9.45 |
| Placebo | Part A: Change From Baseline in Heart Rate | 24 hour | -2.3 Beats per minute | Standard Deviation 6.24 |
| Placebo | Part A: Change From Baseline in Heart Rate | 1 hour | -8.0 Beats per minute | Standard Deviation 5.6 |
| Placebo | Part A: Change From Baseline in Heart Rate | 30 min | -5.3 Beats per minute | Standard Deviation 5.39 |
| 50 µg OD | Part A: Change From Baseline in Heart Rate | 12 hour | 6.4 Beats per minute | Standard Deviation 7.8 |
| 50 µg OD | Part A: Change From Baseline in Heart Rate | 1 hour | -4.8 Beats per minute | Standard Deviation 3.57 |
| 50 µg OD | Part A: Change From Baseline in Heart Rate | 30 min | -5.8 Beats per minute | Standard Deviation 5.4 |
| 50 µg OD | Part A: Change From Baseline in Heart Rate | 24 hour | -1.7 Beats per minute | Standard Deviation 6.69 |
| 50 µg OD | Part A: Change From Baseline in Heart Rate | 6 hour | 4.3 Beats per minute | Standard Deviation 5.58 |
| 100 µg OD | Part A: Change From Baseline in Heart Rate | 30 min | -8.9 Beats per minute | Standard Deviation 8.46 |
| 100 µg OD | Part A: Change From Baseline in Heart Rate | 1 hour | -9.0 Beats per minute | Standard Deviation 8.9 |
| 100 µg OD | Part A: Change From Baseline in Heart Rate | 6 hour | 1.0 Beats per minute | Standard Deviation 9.55 |
| 100 µg OD | Part A: Change From Baseline in Heart Rate | 12 hour | -0.3 Beats per minute | Standard Deviation 10.17 |
| 100 µg OD | Part A: Change From Baseline in Heart Rate | 24 hour | -1.8 Beats per minute | Standard Deviation 8.7 |
| 200 µg OD | Part A: Change From Baseline in Heart Rate | 24 hour | -3.0 Beats per minute | Standard Deviation 7.23 |
| 200 µg OD | Part A: Change From Baseline in Heart Rate | 6 hour | 4.9 Beats per minute | Standard Deviation 5.42 |
| 200 µg OD | Part A: Change From Baseline in Heart Rate | 1 hour | -7.2 Beats per minute | Standard Deviation 5.27 |
| 200 µg OD | Part A: Change From Baseline in Heart Rate | 12 hour | 3.7 Beats per minute | Standard Deviation 6.24 |
| 200 µg OD | Part A: Change From Baseline in Heart Rate | 30 min | -6.1 Beats per minute | Standard Deviation 5.25 |
| 500 µg OD | Part A: Change From Baseline in Heart Rate | 24 hour | -1.8 Beats per minute | Standard Deviation 8.02 |
| 500 µg OD | Part A: Change From Baseline in Heart Rate | 12 hour | 3.7 Beats per minute | Standard Deviation 5.85 |
| 500 µg OD | Part A: Change From Baseline in Heart Rate | 1 hour | -4.3 Beats per minute | Standard Deviation 7.63 |
| 500 µg OD | Part A: Change From Baseline in Heart Rate | 30 min | -6.3 Beats per minute | Standard Deviation 5.37 |
| 500 µg OD | Part A: Change From Baseline in Heart Rate | 6 hour | 7.4 Beats per minute | Standard Deviation 6.37 |
| 1000 µg OD | Part A: Change From Baseline in Heart Rate | 6 hour | -1.3 Beats per minute | Standard Deviation 7.42 |
| 1000 µg OD | Part A: Change From Baseline in Heart Rate | 12 hour | -1.8 Beats per minute | Standard Deviation 8.61 |
| 1000 µg OD | Part A: Change From Baseline in Heart Rate | 30 min | -12.4 Beats per minute | Standard Deviation 6.8 |
| 1000 µg OD | Part A: Change From Baseline in Heart Rate | 24 hour | -6.9 Beats per minute | Standard Deviation 5.88 |
| 1000 µg OD | Part A: Change From Baseline in Heart Rate | 1 hour | -13.0 Beats per minute | Standard Deviation 7.98 |
| 2000 µg OD | Part A: Change From Baseline in Heart Rate | 24 hour | -4.0 Beats per minute | Standard Deviation 8.18 |
| 2000 µg OD | Part A: Change From Baseline in Heart Rate | 6 hour | 2.4 Beats per minute | Standard Deviation 7.98 |
| 2000 µg OD | Part A: Change From Baseline in Heart Rate | 12 hour | 5.3 Beats per minute | Standard Deviation 10.38 |
| 2000 µg OD | Part A: Change From Baseline in Heart Rate | 30 min | -6.1 Beats per minute | Standard Deviation 7.24 |
| 2000 µg OD | Part A: Change From Baseline in Heart Rate | 1 hour | -9.8 Beats per minute | Standard Deviation 7.55 |
Primary
Part A: Change From Baseline in Respiratory Rate
Respiratory rate in part A was assessed in a semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Time frame: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part A: Change From Baseline in Respiratory Rate | 6 hour | 0.1 Breaths per minute | Standard Deviation 2.18 |
| Placebo | Part A: Change From Baseline in Respiratory Rate | 1 hour | -0.3 Breaths per minute | Standard Deviation 2.27 |
| Placebo | Part A: Change From Baseline in Respiratory Rate | 24 hour | -0.6 Breaths per minute | Standard Deviation 2.29 |
| Placebo | Part A: Change From Baseline in Respiratory Rate | 30 min | -0.2 Breaths per minute | Standard Deviation 1.78 |
| Placebo | Part A: Change From Baseline in Respiratory Rate | 12 hour | 0.7 Breaths per minute | Standard Deviation 2.31 |
| 50 µg OD | Part A: Change From Baseline in Respiratory Rate | 12 hour | 0.7 Breaths per minute | Standard Deviation 3.11 |
| 50 µg OD | Part A: Change From Baseline in Respiratory Rate | 30 min | -1.1 Breaths per minute | Standard Deviation 2.81 |
| 50 µg OD | Part A: Change From Baseline in Respiratory Rate | 1 hour | -1.0 Breaths per minute | Standard Deviation 2.76 |
| 50 µg OD | Part A: Change From Baseline in Respiratory Rate | 6 hour | 0.0 Breaths per minute | Standard Deviation 3.67 |
| 50 µg OD | Part A: Change From Baseline in Respiratory Rate | 24 hour | -0.9 Breaths per minute | Standard Deviation 3.2 |
| 100 µg OD | Part A: Change From Baseline in Respiratory Rate | 1 hour | -1.2 Breaths per minute | Standard Deviation 2.17 |
| 100 µg OD | Part A: Change From Baseline in Respiratory Rate | 6 hour | 1.0 Breaths per minute | Standard Deviation 1.95 |
| 100 µg OD | Part A: Change From Baseline in Respiratory Rate | 12 hour | -0.4 Breaths per minute | Standard Deviation 2.43 |
| 100 µg OD | Part A: Change From Baseline in Respiratory Rate | 30 min | -1.5 Breaths per minute | Standard Deviation 1.98 |
| 100 µg OD | Part A: Change From Baseline in Respiratory Rate | 24 hour | -1.0 Breaths per minute | Standard Deviation 2.63 |
| 200 µg OD | Part A: Change From Baseline in Respiratory Rate | 6 hour | 1.0 Breaths per minute | Standard Deviation 2.97 |
| 200 µg OD | Part A: Change From Baseline in Respiratory Rate | 30 min | 0.8 Breaths per minute | Standard Deviation 2.48 |
| 200 µg OD | Part A: Change From Baseline in Respiratory Rate | 12 hour | 1.3 Breaths per minute | Standard Deviation 2.14 |
| 200 µg OD | Part A: Change From Baseline in Respiratory Rate | 24 hour | 0.4 Breaths per minute | Standard Deviation 2.5 |
| 200 µg OD | Part A: Change From Baseline in Respiratory Rate | 1 hour | 0.8 Breaths per minute | Standard Deviation 2.03 |
| 500 µg OD | Part A: Change From Baseline in Respiratory Rate | 6 hour | 0.8 Breaths per minute | Standard Deviation 3.33 |
| 500 µg OD | Part A: Change From Baseline in Respiratory Rate | 24 hour | -0.8 Breaths per minute | Standard Deviation 2.08 |
| 500 µg OD | Part A: Change From Baseline in Respiratory Rate | 12 hour | 0.6 Breaths per minute | Standard Deviation 2.75 |
| 500 µg OD | Part A: Change From Baseline in Respiratory Rate | 1 hour | 0.6 Breaths per minute | Standard Deviation 2.23 |
| 500 µg OD | Part A: Change From Baseline in Respiratory Rate | 30 min | 0.3 Breaths per minute | Standard Deviation 2.01 |
| 1000 µg OD | Part A: Change From Baseline in Respiratory Rate | 30 min | 0.3 Breaths per minute | Standard Deviation 2.74 |
| 1000 µg OD | Part A: Change From Baseline in Respiratory Rate | 1 hour | -0.3 Breaths per minute | Standard Deviation 2.35 |
| 1000 µg OD | Part A: Change From Baseline in Respiratory Rate | 6 hour | 0.6 Breaths per minute | Standard Deviation 2.74 |
| 1000 µg OD | Part A: Change From Baseline in Respiratory Rate | 24 hour | -0.8 Breaths per minute | Standard Deviation 3.15 |
| 1000 µg OD | Part A: Change From Baseline in Respiratory Rate | 12 hour | 0.3 Breaths per minute | Standard Deviation 2.55 |
| 2000 µg OD | Part A: Change From Baseline in Respiratory Rate | 24 hour | -0.4 Breaths per minute | Standard Deviation 1.68 |
| 2000 µg OD | Part A: Change From Baseline in Respiratory Rate | 12 hour | -0.3 Breaths per minute | Standard Deviation 1.86 |
| 2000 µg OD | Part A: Change From Baseline in Respiratory Rate | 1 hour | -0.8 Breaths per minute | Standard Deviation 2.41 |
| 2000 µg OD | Part A: Change From Baseline in Respiratory Rate | 30 min | -0.2 Breaths per minute | Standard Deviation 1.95 |
| 2000 µg OD | Part A: Change From Baseline in Respiratory Rate | 6 hour | 0.3 Breaths per minute | Standard Deviation 2.23 |
Primary
Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Blood pressure in part A was assessed in a semi supine position with a completely automated device. SBP and DBP measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Time frame: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 12 hour | 2.3 Millimeters of mercury | Standard Deviation 6.36 |
| Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 6 hour | 0.1 Millimeters of mercury | Standard Deviation 5.48 |
| Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hour | -0.7 Millimeters of mercury | Standard Deviation 6.19 |
| Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 12 hour | 3.9 Millimeters of mercury | Standard Deviation 6.65 |
| Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 6 hour | 1.3 Millimeters of mercury | Standard Deviation 8.79 |
| Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 1 hour | -3.4 Millimeters of mercury | Standard Deviation 7.72 |
| Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 30 min | -3.2 Millimeters of mercury | Standard Deviation 6.28 |
| Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 1 hour | 0.8 Millimeters of mercury | Standard Deviation 7.02 |
| Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 30 min | 0.3 Millimeters of mercury | Standard Deviation 6.66 |
| Placebo | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hour | -1.3 Millimeters of mercury | Standard Deviation 6.81 |
| 50 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 1 hour | 3.1 Millimeters of mercury | Standard Deviation 4.98 |
| 50 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 30 min | 2.0 Millimeters of mercury | Standard Deviation 6.48 |
| 50 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 6 hour | 0.3 Millimeters of mercury | Standard Deviation 7.41 |
| 50 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 12 hour | 3.1 Millimeters of mercury | Standard Deviation 6.72 |
| 50 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hour | 0.6 Millimeters of mercury | Standard Deviation 6.32 |
| 50 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 30 min | -0.2 Millimeters of mercury | Standard Deviation 5.06 |
| 50 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 1 hour | -1.5 Millimeters of mercury | Standard Deviation 4.74 |
| 50 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 6 hour | 0.7 Millimeters of mercury | Standard Deviation 8.23 |
| 50 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 12 hour | 3.3 Millimeters of mercury | Standard Deviation 6.52 |
| 50 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hour | -0.9 Millimeters of mercury | Standard Deviation 7.54 |
| 100 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 30 min | 2.4 Millimeters of mercury | Standard Deviation 4.91 |
| 100 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 6 hour | -3.8 Millimeters of mercury | Standard Deviation 9.03 |
| 100 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 12 hour | -1.3 Millimeters of mercury | Standard Deviation 8.65 |
| 100 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 1 hour | 3.8 Millimeters of mercury | Standard Deviation 4.65 |
| 100 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hour | 1.5 Millimeters of mercury | Standard Deviation 3.9 |
| 100 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 6 hour | 1.8 Millimeters of mercury | Standard Deviation 3.84 |
| 100 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 12 hour | 2.9 Millimeters of mercury | Standard Deviation 3.45 |
| 100 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 30 min | -3.9 Millimeters of mercury | Standard Deviation 9.67 |
| 100 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hour | -5.3 Millimeters of mercury | Standard Deviation 5.26 |
| 100 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 1 hour | -5.6 Millimeters of mercury | Standard Deviation 8.07 |
| 200 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 12 hour | 4.0 Millimeters of mercury | Standard Deviation 7.92 |
| 200 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 6 hour | 1.9 Millimeters of mercury | Standard Deviation 7.04 |
| 200 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 6 hour | 4.5 Millimeters of mercury | Standard Deviation 7.92 |
| 200 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 1 hour | -3.4 Millimeters of mercury | Standard Deviation 7.01 |
| 200 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hour | 3.6 Millimeters of mercury | Standard Deviation 8.03 |
| 200 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 30 min | 2.0 Millimeters of mercury | Standard Deviation 5.23 |
| 200 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 12 hour | 3.6 Millimeters of mercury | Standard Deviation 4.93 |
| 200 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 1 hour | 1.2 Millimeters of mercury | Standard Deviation 3.63 |
| 200 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 30 min | 0.8 Millimeters of mercury | Standard Deviation 5.16 |
| 200 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hour | 0.0 Millimeters of mercury | Standard Deviation 8.67 |
| 500 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hour | -1.5 Millimeters of mercury | Standard Deviation 6.78 |
| 500 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hour | 3.6 Millimeters of mercury | Standard Deviation 4.21 |
| 500 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 1 hour | -2.2 Millimeters of mercury | Standard Deviation 6.53 |
| 500 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 30 min | -2.3 Millimeters of mercury | Standard Deviation 6.2 |
| 500 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 12 hour | 5.0 Millimeters of mercury | Standard Deviation 9.53 |
| 500 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 6 hour | 2.8 Millimeters of mercury | Standard Deviation 6.34 |
| 500 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 6 hour | 3.2 Millimeters of mercury | Standard Deviation 6.22 |
| 500 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 12 hour | 2.3 Millimeters of mercury | Standard Deviation 6.41 |
| 500 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 1 hour | 4.1 Millimeters of mercury | Standard Deviation 4.44 |
| 500 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 30 min | 2.5 Millimeters of mercury | Standard Deviation 6.2 |
| 1000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 6 hour | -2.0 Millimeters of mercury | Standard Deviation 2.83 |
| 1000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 12 hour | 0.7 Millimeters of mercury | Standard Deviation 4.39 |
| 1000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hour | -2.9 Millimeters of mercury | Standard Deviation 5.62 |
| 1000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hour | -4.3 Millimeters of mercury | Standard Deviation 5.74 |
| 1000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 30 min | -6.1 Millimeters of mercury | Standard Deviation 4.73 |
| 1000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 30 min | -1.6 Millimeters of mercury | Standard Deviation 5.36 |
| 1000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 1 hour | -7.1 Millimeters of mercury | Standard Deviation 9.06 |
| 1000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 6 hour | -0.3 Millimeters of mercury | Standard Deviation 7.48 |
| 1000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 12 hour | 1.6 Millimeters of mercury | Standard Deviation 4.03 |
| 1000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 1 hour | -0.9 Millimeters of mercury | Standard Deviation 7.72 |
| 2000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 6 hour | -0.8 Millimeters of mercury | Standard Deviation 5.86 |
| 2000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 1 hour | -3.9 Millimeters of mercury | Standard Deviation 8.38 |
| 2000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 6 hour | 3.1 Millimeters of mercury | Standard Deviation 7.93 |
| 2000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 1 hour | 0.8 Millimeters of mercury | Standard Deviation 5.04 |
| 2000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hour | -2.8 Millimeters of mercury | Standard Deviation 5.77 |
| 2000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 30 min | -3.3 Millimeters of mercury | Standard Deviation 5.85 |
| 2000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 30 min | 1.9 Millimeters of mercury | Standard Deviation 3.58 |
| 2000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hour | -0.1 Millimeters of mercury | Standard Deviation 5.12 |
| 2000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 12 hour | 3.1 Millimeters of mercury | Standard Deviation 7.76 |
| 2000 µg OD | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 12 hour | 3.3 Millimeters of mercury | Standard Deviation 7.33 |
Primary
Part A: Change From Baseline in Tympanic Temperature
Tympanic temperature in part A was assessed in semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Time frame: Baseline, 30 minutes, 1, 6, 12 and 24 hours post-dose in each treatment period
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part A: Change From Baseline in Tympanic Temperature | 24 hour | -0.06 Celsius | Standard Deviation 0.375 |
| Placebo | Part A: Change From Baseline in Tympanic Temperature | 12 hour | 0.14 Celsius | Standard Deviation 0.478 |
| Placebo | Part A: Change From Baseline in Tympanic Temperature | 30 min | 0.03 Celsius | Standard Deviation 0.313 |
| Placebo | Part A: Change From Baseline in Tympanic Temperature | 1 hour | -0.10 Celsius | Standard Deviation 0.348 |
| Placebo | Part A: Change From Baseline in Tympanic Temperature | 6 hour | 0.20 Celsius | Standard Deviation 0.39 |
| 50 µg OD | Part A: Change From Baseline in Tympanic Temperature | 24 hour | -0.02 Celsius | Standard Deviation 0.233 |
| 50 µg OD | Part A: Change From Baseline in Tympanic Temperature | 1 hour | 0.06 Celsius | Standard Deviation 0.173 |
| 50 µg OD | Part A: Change From Baseline in Tympanic Temperature | 12 hour | 0.31 Celsius | Standard Deviation 0.37 |
| 50 µg OD | Part A: Change From Baseline in Tympanic Temperature | 6 hour | 0.08 Celsius | Standard Deviation 0.259 |
| 50 µg OD | Part A: Change From Baseline in Tympanic Temperature | 30 min | 0.07 Celsius | Standard Deviation 0.21 |
| 100 µg OD | Part A: Change From Baseline in Tympanic Temperature | 1 hour | 0.05 Celsius | Standard Deviation 0.498 |
| 100 µg OD | Part A: Change From Baseline in Tympanic Temperature | 24 hour | -0.02 Celsius | Standard Deviation 0.513 |
| 100 µg OD | Part A: Change From Baseline in Tympanic Temperature | 30 min | 0.04 Celsius | Standard Deviation 0.574 |
| 100 µg OD | Part A: Change From Baseline in Tympanic Temperature | 12 hour | 0.27 Celsius | Standard Deviation 0.542 |
| 100 µg OD | Part A: Change From Baseline in Tympanic Temperature | 6 hour | 0.18 Celsius | Standard Deviation 0.566 |
| 200 µg OD | Part A: Change From Baseline in Tympanic Temperature | 24 hour | 0.03 Celsius | Standard Deviation 0.287 |
| 200 µg OD | Part A: Change From Baseline in Tympanic Temperature | 30 min | 0.05 Celsius | Standard Deviation 0.395 |
| 200 µg OD | Part A: Change From Baseline in Tympanic Temperature | 12 hour | 0.26 Celsius | Standard Deviation 0.355 |
| 200 µg OD | Part A: Change From Baseline in Tympanic Temperature | 1 hour | -0.06 Celsius | Standard Deviation 0.287 |
| 200 µg OD | Part A: Change From Baseline in Tympanic Temperature | 6 hour | 0.07 Celsius | Standard Deviation 0.446 |
| 500 µg OD | Part A: Change From Baseline in Tympanic Temperature | 1 hour | 0.05 Celsius | Standard Deviation 0.478 |
| 500 µg OD | Part A: Change From Baseline in Tympanic Temperature | 30 min | -0.05 Celsius | Standard Deviation 0.366 |
| 500 µg OD | Part A: Change From Baseline in Tympanic Temperature | 6 hour | 0.17 Celsius | Standard Deviation 0.409 |
| 500 µg OD | Part A: Change From Baseline in Tympanic Temperature | 12 hour | 0.20 Celsius | Standard Deviation 0.591 |
| 500 µg OD | Part A: Change From Baseline in Tympanic Temperature | 24 hour | 0.07 Celsius | Standard Deviation 0.392 |
| 1000 µg OD | Part A: Change From Baseline in Tympanic Temperature | 6 hour | 0.14 Celsius | Standard Deviation 0.361 |
| 1000 µg OD | Part A: Change From Baseline in Tympanic Temperature | 30 min | 0.03 Celsius | Standard Deviation 0.287 |
| 1000 µg OD | Part A: Change From Baseline in Tympanic Temperature | 1 hour | 0.12 Celsius | Standard Deviation 0.311 |
| 1000 µg OD | Part A: Change From Baseline in Tympanic Temperature | 24 hour | 0.11 Celsius | Standard Deviation 0.326 |
| 1000 µg OD | Part A: Change From Baseline in Tympanic Temperature | 12 hour | 0.46 Celsius | Standard Deviation 0.4 |
| 2000 µg OD | Part A: Change From Baseline in Tympanic Temperature | 6 hour | 0.19 Celsius | Standard Deviation 0.493 |
| 2000 µg OD | Part A: Change From Baseline in Tympanic Temperature | 30 min | 0.16 Celsius | Standard Deviation 0.385 |
| 2000 µg OD | Part A: Change From Baseline in Tympanic Temperature | 1 hour | 0.10 Celsius | Standard Deviation 0.449 |
| 2000 µg OD | Part A: Change From Baseline in Tympanic Temperature | 24 hour | 0.02 Celsius | Standard Deviation 0.497 |
| 2000 µg OD | Part A: Change From Baseline in Tympanic Temperature | 12 hour | 0.18 Celsius | Standard Deviation 0.622 |
Primary
Part A: Forced Vital Capacity (FVC)
FVC is a measure of lung function and is defined as total amount of air that can be exhaled during FEV1 test. FVC was planned to measured using spirometry. The FVC need to be normal at screening and is part of the Forced Expiratory ratio (FEV1/FVC) which should lie between 0.7-0.8 to indicate no chronic obstruction or restriction. The FVC was therefore only used at screening and requires no ongoing analysis during the study. All other indications of obstruction in the study, e.g. paradoxical bronchospasm was provided by the FEV1. The FVC therefore require no analysis.
Time frame: Day 1 (pre-dose and 1 hour)
Population: Safety Population. Data was not collected for this outcome as FVC was used only at screening and no further analysis during the study was required.
Primary
Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1)
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 using spirometry at the indicated time. FEV1 measurements were repeated until three technically acceptable measurements (within 150 milliliter \[mL\] of each other) were made. Data for FEV1 for part A is presented here.
Time frame: Day 1 (pre-dose and 1 hour)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Pre-dose | 4.389 Liters | Standard Deviation 0.6781 |
| Placebo | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | 1 hour | 4.347 Liters | Standard Deviation 0.6781 |
| 50 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Pre-dose | 4.044 Liters | Standard Deviation 0.6717 |
| 50 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | 1 hour | 4.028 Liters | Standard Deviation 0.7177 |
| 100 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Pre-dose | 4.768 Liters | Standard Deviation 0.8348 |
| 100 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | 1 hour | 4.461 Liters | Standard Deviation 0.4693 |
| 200 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Pre-dose | 3.896 Liters | Standard Deviation 0.7292 |
| 200 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | 1 hour | 3.811 Liters | Standard Deviation 0.6757 |
| 500 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Pre-dose | 4.288 Liters | Standard Deviation 0.5288 |
| 500 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | 1 hour | 4.223 Liters | Standard Deviation 0.5153 |
| 1000 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Pre-dose | 4.036 Liters | Standard Deviation 0.4806 |
| 1000 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | 1 hour | 4.024 Liters | Standard Deviation 0.5971 |
| 2000 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Pre-dose | 4.391 Liters | Standard Deviation 0.5072 |
| 2000 µg OD | Part A: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | 1 hour | 4.435 Liters | Standard Deviation 0.5851 |
Primary
Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE)
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants with 5 percent nSAEs and SAEs has been reported.
Time frame: Up to 12 weeks
Population: Safety Population comprised of all randomized participants who took at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | nSAE | 6 Participants |
| Placebo | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | SAE | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | nSAE | 9 Participants |
| 50 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | SAE | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | nSAE | 6 Participants |
| 100 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | SAE | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | nSAE | 7 Participants |
| 200 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | SAE | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | nSAE | 6 Participants |
| 500 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | SAE | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | nSAE | 4 Participants |
| 1000 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | SAE | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | nSAE | 5 Participants |
| 2000 µg OD | Part A: Number of Participants With Any Non-serious Adverse Event (nSAE) and Any Serious Adverse Event (SAE) | SAE | 0 Participants |
Primary
Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC)
Number of participants with clinical chemistry values that changed from normal to high or low in part A are presented. Chemistry parameters for which PCC values were identified were: Alkaline Phosphatase, Alanine Amino Transferase, aspartate aminotransferase, Total Bilirubin, calcium, glucose, potassium and Sodium.
Time frame: 24 hours post-dose in each treatment period.
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Total Bilirubin; to high | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to low | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to high | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to low | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to high | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to low | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alanine Amino Transferase; to high | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alkaline Phosphatase; to high | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to high | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Aspartate Amino Transferase; to high | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to low | 0 Participants |
| Placebo | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to high | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to low | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to low | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to high | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to high | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to high | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to low | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to high | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Total Bilirubin; to high | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to low | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Aspartate Amino Transferase; to high | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alkaline Phosphatase; to high | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alanine Amino Transferase; to high | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to low | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alkaline Phosphatase; to high | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alanine Amino Transferase; to high | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Aspartate Amino Transferase; to high | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Total Bilirubin; to high | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to high | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to low | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to high | 1 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to low | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to high | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to low | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to high | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to high | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to low | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to high | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Aspartate Amino Transferase; to high | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Total Bilirubin; to high | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to low | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to low | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alanine Amino Transferase; to high | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to high | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alkaline Phosphatase; to high | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to low | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to high | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alanine Amino Transferase; to high | 1 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to high | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to low | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Total Bilirubin; to high | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to high | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Aspartate Amino Transferase; to high | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to high | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to high | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alkaline Phosphatase; to high | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to low | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to low | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to low | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to low | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Aspartate Amino Transferase; to high | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to high | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to low | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alanine Amino Transferase; to high | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to high | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to low | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to low | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alkaline Phosphatase; to high | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Total Bilirubin; to high | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to high | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to high | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Aspartate Amino Transferase; to high | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alanine Amino Transferase; to high | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to low | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to high | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to low | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Total Bilirubin; to high | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Alkaline Phosphatase; to high | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Sodium; to high | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to high | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Glucose; to low | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Calcium; to high | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Clinical Chemistry Values of Potential Clinical Importance Criteria (PCC) | Potassium; to low | 0 Participants |
Primary
Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities
Triplicate/Single 12-lead ECG was obtained using an automated ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTFc intervals. Number of participants with abnormal clinically significant and abnormal-not clinically significant values at any time post-Baseline is presented.
Time frame: Day 1 of each treatment period
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - not clinically significant | 2 Participants |
| Placebo | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - clinically significant | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - not clinically significant | 2 Participants |
| 50 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - clinically significant | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - not clinically significant | 1 Participants |
| 100 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - clinically significant | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - not clinically significant | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - clinically significant | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - not clinically significant | 1 Participants |
| 500 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - clinically significant | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - not clinically significant | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - clinically significant | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - not clinically significant | 1 Participants |
| 2000 µg OD | Part A: Number of Participants With Electrocardiogram (ECG) Abnormalities | Abnormal - clinically significant | 0 Participants |
Primary
Part A: Number of Participants With Hematology Values of PCC
Number of participants with hematology parameters of PCC which shifted from normal to high in part A are presented. Hematology parameters for which PCC values were identified were: Hemoglobin, Hematocrit, Lymphocytes, Total Neutrophils, Platelet count and White Blood Cell (WBC) Count. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles)
Time frame: 24 hours post-dose in each treatment period
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part A: Number of Participants With Hematology Values of PCC | Platelet count;to high;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| Placebo | Part A: Number of Participants With Hematology Values of PCC | WBC count,to low,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| Placebo | Part A: Number of Participants With Hematology Values of PCC | Hematocrit; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| Placebo | Part A: Number of Participants With Hematology Values of PCC | Lymphocytes; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| Placebo | Part A: Number of Participants With Hematology Values of PCC | Platelet count; to low;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| Placebo | Part A: Number of Participants With Hematology Values of PCC | Total Neutrophils; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| Placebo | Part A: Number of Participants With Hematology Values of PCC | WBC count,to high,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| Placebo | Part A: Number of Participants With Hematology Values of PCC | Hemoglobin; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count;to high;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hemoglobin; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count; to low;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hematocrit; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to low,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Hematology Values of PCC | Lymphocytes; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to high,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 50 µg OD | Part A: Number of Participants With Hematology Values of PCC | Total Neutrophils; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Hematology Values of PCC | Lymphocytes; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count;to high;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Hematology Values of PCC | Total Neutrophils; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hemoglobin; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to high,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hematocrit; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to low,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 100 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count; to low;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hematocrit; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hemoglobin; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Hematology Values of PCC | Total Neutrophils; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count;to high;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Hematology Values of PCC | Lymphocytes; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count; to low;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to high,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 200 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to low,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Hematology Values of PCC | Total Neutrophils; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to low,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Hematology Values of PCC | Lymphocytes; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count; to low;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hematocrit; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to high,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count;to high;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 500 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hemoglobin; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count; to low;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to low,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hemoglobin; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hematocrit; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Total Neutrophils; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Lymphocytes; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to high,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 1000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count;to high;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hemoglobin; to high,n=23,12,12,13,12,9,12 | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to low,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Total Neutrophils; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Hematology Values of PCC | WBC count,to high,n=23, 12, 12, 13, 12, 9, 12 | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count;to high;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Lymphocytes; to low,n=23,12,12,13,12,9,12 | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Platelet count; to low;n=23, 12, 11, 13, 11, 9, 11 | 0 Participants |
| 2000 µg OD | Part A: Number of Participants With Hematology Values of PCC | Hematocrit; to high,n=23,12,12,13,12,9,12 | 0 Participants |
Primary
Part B: Change From Baseline in Heart Rate
Heart rate in part B was assessed in a semi supine position with a completely automated device. Heart rate measurement was preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Time frame: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part B: Change From Baseline in Heart Rate | Day 9, pre-dose | 1.7 Beats per minute | Standard Deviation 5.13 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 5, pre-dose | -2.3 Beats per minute | Standard Deviation 9.45 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 10, pre-dose | 1.0 Beats per minute | Standard Deviation 11.79 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 6, pre-dose | -2.7 Beats per minute | Standard Deviation 8.14 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 11, pre-dose | -1.3 Beats per minute | Standard Deviation 14.64 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 2, pre-dose | -0.3 Beats per minute | Standard Deviation 6.11 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 14, pre-dose | 6.0 Beats per minute | Standard Deviation 11.27 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 7, pre-dose | 3.7 Beats per minute | Standard Deviation 9.07 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 14, 24 hours | -2.3 Beats per minute | Standard Deviation 7.57 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 12, pre-dose | -5.7 Beats per minute | Standard Deviation 7.23 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 4, pre-dose | 6.7 Beats per minute | Standard Deviation 11.5 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 13, pre-dose | 4.0 Beats per minute | Standard Deviation 15 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 8, pre-dose | 4.7 Beats per minute | Standard Deviation 13.5 |
| Placebo | Part B: Change From Baseline in Heart Rate | Day 3, pre-dose | 3.0 Beats per minute | Standard Deviation 6.56 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 14, 24 hours | -2.2 Beats per minute | Standard Deviation 7.56 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 2, pre-dose | -0.7 Beats per minute | Standard Deviation 7.14 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 3, pre-dose | 0.0 Beats per minute | Standard Deviation 6.76 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 4, pre-dose | -2.2 Beats per minute | Standard Deviation 8.03 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 6, pre-dose | -6.4 Beats per minute | Standard Deviation 7.8 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 7, pre-dose | -0.8 Beats per minute | Standard Deviation 11.12 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 8, pre-dose | -3.2 Beats per minute | Standard Deviation 5.85 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 9, pre-dose | -3.4 Beats per minute | Standard Deviation 8.49 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 10, pre-dose | -2.7 Beats per minute | Standard Deviation 10.28 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 11, pre-dose | -2.8 Beats per minute | Standard Deviation 11.98 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 14, pre-dose | -5.8 Beats per minute | Standard Deviation 9.36 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 12, pre-dose | -4.9 Beats per minute | Standard Deviation 6.47 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 13, pre-dose | -4.4 Beats per minute | Standard Deviation 6.13 |
| 50 µg OD | Part B: Change From Baseline in Heart Rate | Day 5, pre-dose | -3.2 Beats per minute | Standard Deviation 9.26 |
Primary
Part B: Change From Baseline in Respiratory Rate
Respiratory rate in part B was assessed in a semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Time frame: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 2, pre-dose | -2.3 Breaths per minute | Standard Deviation 0.58 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 3, pre-dose | -2.3 Breaths per minute | Standard Deviation 2.31 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 4, pre-dose | -2.3 Breaths per minute | Standard Deviation 2.08 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 5, pre-dose | -2.7 Breaths per minute | Standard Deviation 2.31 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 6, pre-dose | -2.7 Breaths per minute | Standard Deviation 0.58 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 7, pre-dose | -2.3 Breaths per minute | Standard Deviation 2.31 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 8, pre-dose | -2.7 Breaths per minute | Standard Deviation 0.58 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 9, pre-dose | -2.0 Breaths per minute | Standard Deviation 2 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 10, pre-dose | -1.7 Breaths per minute | Standard Deviation 2.31 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 11, pre-dose | -3.3 Breaths per minute | Standard Deviation 0.58 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 12, pre-dose | -2.3 Breaths per minute | Standard Deviation 1.15 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 13, pre-dose | -1.3 Breaths per minute | Standard Deviation 1.15 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 14, pre-dose | -2.0 Breaths per minute | Standard Deviation 1.73 |
| Placebo | Part B: Change From Baseline in Respiratory Rate | Day 14, 24 hours | -2.3 Breaths per minute | Standard Deviation 1.53 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 12, pre-dose | -1.0 Breaths per minute | Standard Deviation 2.74 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 2, pre-dose | -0.6 Breaths per minute | Standard Deviation 3.17 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 9, pre-dose | 0.1 Breaths per minute | Standard Deviation 2.98 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 3, pre-dose | -1.0 Breaths per minute | Standard Deviation 3.2 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 14, pre-dose | -1.1 Breaths per minute | Standard Deviation 2.89 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 4, pre-dose | -0.3 Breaths per minute | Standard Deviation 2.96 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 10, pre-dose | -1.2 Breaths per minute | Standard Deviation 2.54 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 5, pre-dose | -1.4 Breaths per minute | Standard Deviation 2.65 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 13, pre-dose | -0.1 Breaths per minute | Standard Deviation 3.06 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 6, pre-dose | -1.6 Breaths per minute | Standard Deviation 2.92 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 11, pre-dose | -0.9 Breaths per minute | Standard Deviation 3.62 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 7, pre-dose | -0.8 Breaths per minute | Standard Deviation 2.59 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 14, 24 hours | -1.1 Breaths per minute | Standard Deviation 2.26 |
| 50 µg OD | Part B: Change From Baseline in Respiratory Rate | Day 8, pre-dose | -0.7 Breaths per minute | Standard Deviation 2.45 |
Primary
Part B: Change From Baseline in SBP and DBP
Blood pressure in part B were assessed in semi supine position with a completely automated device. SBP and DBP preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Time frame: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 3, pre-dose | -0.7 Millimeters of mercury | Standard Deviation 9.07 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 6, pre-dose | -7.7 Millimeters of mercury | Standard Deviation 10.02 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 4, pre-dose | 2.3 Millimeters of mercury | Standard Deviation 10.5 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 11, pre-dose | -9.3 Millimeters of mercury | Standard Deviation 12.74 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 5, pre-dose | -1.0 Millimeters of mercury | Standard Deviation 9.85 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 3, pre-dose | -8.3 Millimeters of mercury | Standard Deviation 9.45 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 6, pre-dose | -1.7 Millimeters of mercury | Standard Deviation 8.5 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 12, pre-dose | -7.3 Millimeters of mercury | Standard Deviation 7.51 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 7, pre-dose | -4.7 Millimeters of mercury | Standard Deviation 5.86 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 7, pre-dose | -8.3 Millimeters of mercury | Standard Deviation 9.45 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 8, pre-dose | -1.3 Millimeters of mercury | Standard Deviation 8.08 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 13, pre-dose | -7.0 Millimeters of mercury | Standard Deviation 10.58 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 9, pre-dose | 0.0 Millimeters of mercury | Standard Deviation 3.61 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 11, pre-dose | -6.3 Millimeters of mercury | Standard Deviation 5.51 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 5, pre-dose | -10.7 Millimeters of mercury | Standard Deviation 11.72 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 12, pre-dose | -6.3 Millimeters of mercury | Standard Deviation 4.73 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 14, pre-dose | -8.3 Millimeters of mercury | Standard Deviation 10.97 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 13, pre-dose | 2.3 Millimeters of mercury | Standard Deviation 4.93 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 9, pre-dose | -6.3 Millimeters of mercury | Standard Deviation 11.93 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 14, pre-dose | -1.7 Millimeters of mercury | Standard Deviation 7.57 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 14, 24 hours | -1.3 Millimeters of mercury | Standard Deviation 1.53 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 14, 24 hours | -0.7 Millimeters of mercury | Standard Deviation 2.08 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 4, pre-dose | -7.3 Millimeters of mercury | Standard Deviation 12.1 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 8, pre-dose | -5.7 Millimeters of mercury | Standard Deviation 12.42 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 2, pre-dose | 3.3 Millimeters of mercury | Standard Deviation 11.24 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 10, pre-dose | -8.7 Millimeters of mercury | Standard Deviation 11.93 |
| Placebo | Part B: Change From Baseline in SBP and DBP | SBP, Day 10, pre-dose | -4.7 Millimeters of mercury | Standard Deviation 5.13 |
| Placebo | Part B: Change From Baseline in SBP and DBP | DBP, Day 2, pre-dose | -6.0 Millimeters of mercury | Standard Deviation 10.15 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 10, pre-dose | -5.2 Millimeters of mercury | Standard Deviation 6.65 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 2, pre-dose | -3.0 Millimeters of mercury | Standard Deviation 4.72 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 3, pre-dose | -1.3 Millimeters of mercury | Standard Deviation 5.85 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 4, pre-dose | -3.4 Millimeters of mercury | Standard Deviation 4.9 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 5, pre-dose | -2.2 Millimeters of mercury | Standard Deviation 5.09 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 6, pre-dose | -3.7 Millimeters of mercury | Standard Deviation 4.72 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 7, pre-dose | -2.3 Millimeters of mercury | Standard Deviation 3.57 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 9, pre-dose | -2.8 Millimeters of mercury | Standard Deviation 4.02 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 10, pre-dose | -0.6 Millimeters of mercury | Standard Deviation 6.21 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 11, pre-dose | -2.1 Millimeters of mercury | Standard Deviation 4.46 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 12, pre-dose | -2.9 Millimeters of mercury | Standard Deviation 4.23 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 13, pre-dose | -3.0 Millimeters of mercury | Standard Deviation 5.43 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 14, pre-dose | -3.2 Millimeters of mercury | Standard Deviation 3.83 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 14, 24 hours | -1.0 Millimeters of mercury | Standard Deviation 5.17 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 2, pre-dose | -5.4 Millimeters of mercury | Standard Deviation 7.6 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 3, pre-dose | -0.1 Millimeters of mercury | Standard Deviation 8.7 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 4, pre-dose | -4.1 Millimeters of mercury | Standard Deviation 7.75 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 5, pre-dose | -5.1 Millimeters of mercury | Standard Deviation 8.74 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 6, pre-dose | -7.2 Millimeters of mercury | Standard Deviation 7.26 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 7, pre-dose | -5.0 Millimeters of mercury | Standard Deviation 9.5 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 8, pre-dose | -7.6 Millimeters of mercury | Standard Deviation 10.01 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 11, pre-dose | -4.4 Millimeters of mercury | Standard Deviation 9.06 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 12, pre-dose | -5.4 Millimeters of mercury | Standard Deviation 6.54 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 13, pre-dose | -4.9 Millimeters of mercury | Standard Deviation 6.51 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 14, pre-dose | -4.6 Millimeters of mercury | Standard Deviation 7.33 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 14, 24 hours | -3.7 Millimeters of mercury | Standard Deviation 6.71 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | DBP, Day 8, pre-dose | -4.3 Millimeters of mercury | Standard Deviation 3.91 |
| 50 µg OD | Part B: Change From Baseline in SBP and DBP | SBP, Day 9, pre-dose | -5.8 Millimeters of mercury | Standard Deviation 4.27 |
Primary
Part B: Change From Baseline in Tympanic Temperature
Tympanic temperature in part B was assessed in semi supine position after 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as measurements done on Day -1. Change from Baseline was defined as the value at indicated time point minus Baseline value. Baseline was defined as latest pre-dose measurement. Change from Baseline was defined as the value at indicated time point minus Baseline value.
Time frame: Baseline, Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 3, pre-dose | 0.03 Celsius | Standard Deviation 0.379 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 13, pre-dose | 0.07 Celsius | Standard Deviation 0.513 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 9, pre-dose | -0.03 Celsius | Standard Deviation 0.153 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 14, pre-dose | 0.17 Celsius | Standard Deviation 0.115 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 4, pre-dose | 0.13 Celsius | Standard Deviation 0.153 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 14, 24 hours | 0.17 Celsius | Standard Deviation 0.115 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 10, pre-dose | 0.13 Celsius | Standard Deviation 0.451 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 5, pre-dose | 0.13 Celsius | Standard Deviation 0.404 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 7, pre-dose | -0.10 Celsius | Standard Deviation 0.1 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 6, pre-dose | 0.10 Celsius | Standard Deviation 0.265 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 8, pre-dose | -0.27 Celsius | Standard Deviation 0.231 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 12, pre-dose | 0.00 Celsius | Standard Deviation 0.265 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 11, pre-dose | 0.13 Celsius | Standard Deviation 0.306 |
| Placebo | Part B: Change From Baseline in Tympanic Temperature | Day 2, pre-dose | 0.17 Celsius | Standard Deviation 0.058 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 11, pre-dose | 0.34 Celsius | Standard Deviation 0.343 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 2, pre-dose | 0.26 Celsius | Standard Deviation 0.477 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 3, pre-dose | 0.37 Celsius | Standard Deviation 0.45 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 4, pre-dose | 0.26 Celsius | Standard Deviation 0.416 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 6, pre-dose | 0.31 Celsius | Standard Deviation 0.322 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 7, pre-dose | 0.41 Celsius | Standard Deviation 0.448 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 9, pre-dose | 0.21 Celsius | Standard Deviation 0.326 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 10, pre-dose | 0.31 Celsius | Standard Deviation 0.392 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 12, pre-dose | 0.32 Celsius | Standard Deviation 0.415 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 13, pre-dose | 0.33 Celsius | Standard Deviation 0.466 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 14, pre-dose | 0.32 Celsius | Standard Deviation 0.458 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 14, 24 hours | 0.32 Celsius | Standard Deviation 0.502 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 5, pre-dose | 0.34 Celsius | Standard Deviation 0.445 |
| 50 µg OD | Part B: Change From Baseline in Tympanic Temperature | Day 8, pre-dose | 0.29 Celsius | Standard Deviation 0.462 |
Primary
Part B: Forced Vital Capacity (FVC)
FVC is a measure of lung function and is defined as total amount of air that can be exhaled during FEV1 test. FVC was planned to measured using spirometry. The FVC need to be normal at screening and is part of the Forced Expiratory ratio (FEV1/FVC) which should lie between 0.7-0.8 to indicate no chronic obstruction or restriction. The FVC was therefore only used at screening and requires no ongoing analysis during the study. All other indications of obstruction in the study, e.g. paradoxical bronchospasm was provided by the FEV1. The FVC therefore require no analysis.
Time frame: Day 1 (pre-dose and 1 hour)
Population: Safety Population. Data was not collected for this outcome as FVC was used only at screening and no further analysis during the study was required.
Primary
Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1)
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 using spirometry at the indicated time. Existing spirometry equipment was used. FEV1 measurements were repeated until three technically acceptable measurements (within 150 mL of each other) were made. Data for FEV1 for part B is presented here.
Time frame: Up to Day 14
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 1,1 hour | 4.323 Liters | Standard Deviation 0.0981 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 2,pre-dose | 4.357 Liters | Standard Deviation 0.0551 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 2,1 hour | 4.373 Liters | Standard Deviation 0.0569 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 3,pre-dose | 4.407 Liters | Standard Deviation 0.1504 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 3,1 hour | 4.460 Liters | Standard Deviation 0.2771 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 4,pre-dose | 4.447 Liters | Standard Deviation 0.1159 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 4,1 hour | 4.307 Liters | Standard Deviation 0.106 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 5,pre-dose | 4.290 Liters | Standard Deviation 0.1082 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 5,1 hour | 4.480 Liters | Standard Deviation 0.26 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 6,1 hour | 4.533 Liters | Standard Deviation 0.3177 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 7,pre-dose | 4.467 Liters | Standard Deviation 0.2386 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 7,1 hour | 4.400 Liters | Standard Deviation 0.2207 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 8,pre-dose | 4.383 Liters | Standard Deviation 0.0351 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 8,1 hour | 4.440 Liters | Standard Deviation 0.1229 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 9,pre-dose | 4.483 Liters | Standard Deviation 0.2458 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 10,pre-dose | 4.443 Liters | Standard Deviation 0.1419 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 10,1 hour | 4.583 Liters | Standard Deviation 0.1914 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 11,pre-dose | 4.423 Liters | Standard Deviation 0.1422 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 11,1 hour | 4.463 Liters | Standard Deviation 0.254 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 12,pre-dose | 4.417 Liters | Standard Deviation 0.1258 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 12,1 hour | 4.440 Liters | Standard Deviation 0.0917 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 13,pre-dose | 4.400 Liters | Standard Deviation 0.2252 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 13,1 hour | 4.653 Liters | Standard Deviation 0.2146 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 14,pre-dose | 4.533 Liters | Standard Deviation 0.0666 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 14,1 hour | 4.557 Liters | Standard Deviation 0.1701 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day -1 | 4.333 Liters | Standard Deviation 0.1739 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 1,pre-dose | 4.277 Liters | Standard Deviation 0.0987 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 6,pre-dose | 4.300 Liters | Standard Deviation 0.0173 |
| Placebo | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 9,1 hour | 4.470 Liters | Standard Deviation 0.1179 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 9,pre-dose | 4.512 Liters | Standard Deviation 0.7483 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day -1 | 4.570 Liters | Standard Deviation 0.6275 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 2,pre-dose | 4.446 Liters | Standard Deviation 0.723 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 10,pre-dose | 4.473 Liters | Standard Deviation 0.6942 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 2,1 hour | 4.486 Liters | Standard Deviation 0.6828 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 13,1 hour | 4.768 Liters | Standard Deviation 0.7609 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 3,pre-dose | 4.474 Liters | Standard Deviation 0.6999 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 10,1 hour | 4.582 Liters | Standard Deviation 0.7609 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 3,1 hour | 4.493 Liters | Standard Deviation 0.6548 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 9,1 hour | 4.627 Liters | Standard Deviation 0.7737 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 4,pre-dose | 4.483 Liters | Standard Deviation 0.7241 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 11,pre-dose | 4.570 Liters | Standard Deviation 0.7944 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 4,1 hour | 4.519 Liters | Standard Deviation 0.7444 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 14,pre-dose | 4.541 Liters | Standard Deviation 0.8512 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 5,pre-dose | 4.494 Liters | Standard Deviation 0.8042 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 11,1 hour | 4.609 Liters | Standard Deviation 0.746 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 5,1 hour | 4.486 Liters | Standard Deviation 0.7647 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 6,pre-dose | 4.498 Liters | Standard Deviation 0.7086 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 1,pre-dose | 4.408 Liters | Standard Deviation 0.6852 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 6,1 hour | 4.573 Liters | Standard Deviation 0.7994 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 12,pre-dose | 4.599 Liters | Standard Deviation 0.7469 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 7,pre-dose | 4.503 Liters | Standard Deviation 0.8559 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 14,1 hour | 4.609 Liters | Standard Deviation 0.8102 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 7,1 hour | 4.581 Liters | Standard Deviation 0.8018 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 12,1 hour | 4.600 Liters | Standard Deviation 0.7029 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 8,pre-dose | 4.449 Liters | Standard Deviation 0.7952 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 1,1 hour | 4.413 Liters | Standard Deviation 0.6931 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 8,1 hour | 4.572 Liters | Standard Deviation 0.6952 |
| 50 µg OD | Part B: Maximal Amount of Air Forcefully Exhaled in 1 Second (FEV1) | Day 13,pre-dose | 4.514 Liters | Standard Deviation 0.7352 |
Primary
Part B: Number of Participants With Any AE and Any SAE
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants with 5 percent nSAEs and SAEs has been reported.
Time frame: Up to 4 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part B: Number of Participants With Any AE and Any SAE | nSAE | 3 Participants |
| Placebo | Part B: Number of Participants With Any AE and Any SAE | SAE | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Any AE and Any SAE | nSAE | 8 Participants |
| 50 µg OD | Part B: Number of Participants With Any AE and Any SAE | SAE | 0 Participants |
Primary
Part B: Number of Participants With Clinical Chemistry Values of PCC
Number of participants with clinical chemistry values that changed from normal to high or low in part B are presented. Chemistry parameters for which PCC values were identified were: Alkaline Phosphatase, Alanine Amino Transferase, aspartate aminotransferase, Total Bilirubin, calcium, glucose, potassium and Sodium. Only participants with data available at specified time points were analyzed (represented by n=X in category titles)
Time frame: Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 10;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 14,pre dose,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 14,pre dose,to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 14,24 hours,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 12;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 2;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 8;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 2;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 14,pre-dose;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 4;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 14,24 hour ,to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 4;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 2;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 14,24 hour;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 6;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 4;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 8;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 14,24 hour,to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 8;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 4;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 10;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 8, to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 10;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 8;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 12;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 2, to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 12;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 10;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 14,pre dose,to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 12;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 14,pre dose,to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 14,pre dose;to n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 14,24 hour,to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 10;to high,,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 14,24 hour,to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 14,24 hour;to hn=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 2;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 6, to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 2;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 2;to high,n=3,8 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 4;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 4,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 4;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 4;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 6;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 10, to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 6;to low, n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 6;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 8;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 10,to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 8;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 8;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 10;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 10, to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 10;to low,,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 10;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 12;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 12;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 12;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 14,24 hour, to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 14;pre dose,to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 14,pre dose;n=2,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 14;pre dose,to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 12,to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 14;24 hours,to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 14,24 hour,n=3,8 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 14;24 hours,to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 2;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 2;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 2,;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 2;to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 6;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 6,to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 4;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 12;to high,,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 4;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 2, to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 4, to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 6;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 4, to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 6, to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 14,pre dose,to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 8, to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 8;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 8, to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 6;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 12, to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 6;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 12, to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 10;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 14,pre dose, to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 6;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 14,pre dose, to low,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 12;to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 14,24 hour, to high,n=3,9 | 0 Participants |
| Placebo | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 8;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 14,24 hour, to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 8;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 4;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 10;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 2;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 4;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 4,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 6,to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 8;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 8, to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 10;to high,,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 12;to high,,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 12,to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 14,pre dose,to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 14,pre dose,to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 14,24 hour ,to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 2, to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 2, to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 4, to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 6, to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 10, to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 10, to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 14,24 hour, to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 2;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 4;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 6;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 10;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 12;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 14,pre-dose;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alkaline Phosphatase,Day 14,24 hour;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 2;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 6;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 8;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 12;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 14,pre dose;to n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Alanine Amino Transferase,Day 14,24 hour;to hn=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 2;to high,n=3,8 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 4;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 6;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 8;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 10;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 12;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 14,pre dose;n=2,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Aspartate Amino Transferase,Day 14,24 hour,n=3,8 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 2,;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 4;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 6;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 8;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 10;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 12;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 14,pre dose,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Total Bilirubin,Day 14,24 hours,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 2;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 2;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 4;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 4;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 6;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 6;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 8;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 8;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 10;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 10;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 12;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 12;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 14,pre dose,to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 14,pre dose,to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 14,24 hour,to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Calcium,Day 14,24 hour,to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 2;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 2;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 4;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 4;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 6;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 6;to low, n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 8;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 8;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 10;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 10;to low,,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 12;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 12;to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 14;pre dose,to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 14;pre dose,to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 14;24 hours,to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Glucose,Day 14;24 hours,to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 2;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 6;to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 10,to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Potassium,Day 14,24 hour,to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 4, to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 6, to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 8, to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 8, to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 12, to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 12, to low,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 14,pre dose, to high,n=3,9 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Clinical Chemistry Values of PCC | Sodium,Day 14,pre dose, to low,n=3,9 | 0 Participants |
Primary
Part B: Number of Participants With ECG Abnormalities
Triplicate/Single 12-lead ECG was obtained using an automated ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTFc intervals. Number of participants with abnormal clinically significant and abnormal-not clinically significant values at any time post-Baseline is presented.
Time frame: Pre-dose on Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14, 24 hours post-dose on Day 14
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part B: Number of Participants With ECG Abnormalities | Abnormal - not clinically significant | 1 Participants |
| Placebo | Part B: Number of Participants With ECG Abnormalities | Abnormal - clinically significant | 0 Participants |
| 50 µg OD | Part B: Number of Participants With ECG Abnormalities | Abnormal - not clinically significant | 2 Participants |
| 50 µg OD | Part B: Number of Participants With ECG Abnormalities | Abnormal - clinically significant | 0 Participants |
Primary
Part B: Number of Participants With Hematology Values of PCC
Number of participants with hematology parameters of PCC which shifted from normal to high in part B are presented. Hematology parameters for which PCC values were identified were: Hemoglobin, Hematocrit, Lymphocytes, Total Neutrophils, Platelet count and WBC count
Time frame: Pre-dose on Days 2, 4, 6, 8, 10, 12, and 14, 24 hours post-dose on Day 14
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 10 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 6 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 8 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 10 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 12 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 4 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 14,pre dose | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 14,24 hour | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 2 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 4 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 6 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 8 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 2 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 12 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 14,pre dose | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 14,24 hour | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 2 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 4 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 6 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 8 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 10 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 12 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 14,pre dose | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 14,24 hour | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 2 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 4 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 6 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 8 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 10 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 12 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 14,pre dose | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 14,24 hour | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 2 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 4 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 6 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 8 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 10 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 12 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 14,pre dose | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 14,24 hour | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 2 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 4 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 6 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 8 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 10 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 12 | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 14,pre dose | 0 Participants |
| Placebo | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 14,24 hour | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 14,pre dose | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 2 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 4 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 2 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 6 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 10 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 8 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 4 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 10 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 6 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 12 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 6 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 12 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 14,pre dose | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 8 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hemoglobin,Day 14,24 hour | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 12 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 2 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 10 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 4 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 14,pre dose | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 6 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 12 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 8 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 8 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 10 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 14,pre dose | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 12 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 14,24 hour | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 14,pre dose | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Total Neutrophils,Day 14,24 hour | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Hematocrit,Day 14,24 hour | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 14,24 hour | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 2 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 2 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 4 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 2 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 6 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 4 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 8 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 10 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 10 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 6 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 12 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | WBC count,Day 4 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 14,pre dose | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Platelet count,Day 8 | 0 Participants |
| 50 µg OD | Part B: Number of Participants With Hematology Values of PCC | Lymphocytes,Day 14,24 hour | 0 Participants |
Secondary
Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for AUC (0 to t), AUC (0 to 24) and AUC (0 to inf) of GSK2292767 for part A is presented. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). Pharmacokinetic population comprised of participants in the 'All participant' population for whom a pharmacokinetic sample was obtained and analyzed.
Time frame: Pre-dose (5 minutes (min), 30 min, 45 min, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-t);n=12,12,12,12,9,12 | 69.5822 Hours*picograms per milliliter | Geometric Coefficient of Variation 133.1 |
| 50 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-t);n=12,12,12,12,9,12 | 337.0775 Hours*picograms per milliliter | Geometric Coefficient of Variation 48.3 |
| 50 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC(0-inf);n=0,2,5,7,6,10 | 596.4042 Hours*picograms per milliliter | Geometric Coefficient of Variation 10.1 |
| 50 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-24);n=0,2,5,10,8,11 | 596.1161 Hours*picograms per milliliter | Geometric Coefficient of Variation 10 |
| 100 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC(0-inf);n=0,2,5,7,6,10 | 724.6058 Hours*picograms per milliliter | Geometric Coefficient of Variation 57.8 |
| 100 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-t);n=12,12,12,12,9,12 | 633.3267 Hours*picograms per milliliter | Geometric Coefficient of Variation 59.6 |
| 100 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-24);n=0,2,5,10,8,11 | 721.9301 Hours*picograms per milliliter | Geometric Coefficient of Variation 57.9 |
| 200 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-t);n=12,12,12,12,9,12 | 2164.3817 Hours*picograms per milliliter | Geometric Coefficient of Variation 72.3 |
| 200 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-24);n=0,2,5,10,8,11 | 2460.3695 Hours*picograms per milliliter | Geometric Coefficient of Variation 70.3 |
| 200 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC(0-inf);n=0,2,5,7,6,10 | 2211.9120 Hours*picograms per milliliter | Geometric Coefficient of Variation 81.5 |
| 500 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC(0-inf);n=0,2,5,7,6,10 | 3709.6509 Hours*picograms per milliliter | Geometric Coefficient of Variation 40.6 |
| 500 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-24);n=0,2,5,10,8,11 | 3689.7545 Hours*picograms per milliliter | Geometric Coefficient of Variation 36 |
| 500 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-t);n=12,12,12,12,9,12 | 3440.6354 Hours*picograms per milliliter | Geometric Coefficient of Variation 37.1 |
| 1000 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-24);n=0,2,5,10,8,11 | 7781.2593 Hours*picograms per milliliter | Geometric Coefficient of Variation 52.5 |
| 1000 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC (0-t);n=12,12,12,12,9,12 | 7758.9831 Hours*picograms per milliliter | Geometric Coefficient of Variation 50.9 |
| 1000 µg OD | Part A: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2292767 | AUC(0-inf);n=0,2,5,7,6,10 | 8383.6427 Hours*picograms per milliliter | Geometric Coefficient of Variation 57.8 |
90% CI: [0.27, 0.61]
90% CI: [0.65, 1.47]
90% CI: [1.01, 1.74]
90% CI: [0.69, 1.62]
90% CI: [0.95, 1.64]
Secondary
Part A: Maximum Observed Plasma Drug Concentration (Cmax) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Five min post dose concentrations on Days 2-13 were assumed to be the Cmax values. Data for Cmax of GSK2292767 for part A is presented. Cmax is defined as maximum observed plasma concentration of GSK2292767.
Time frame: Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part A: Maximum Observed Plasma Drug Concentration (Cmax) of GSK2292767 | 36.9018 Picograms per milliliter | Geometric Coefficient of Variation 31.9 |
| 50 µg OD | Part A: Maximum Observed Plasma Drug Concentration (Cmax) of GSK2292767 | 90.8927 Picograms per milliliter | Geometric Coefficient of Variation 30.6 |
| 100 µg OD | Part A: Maximum Observed Plasma Drug Concentration (Cmax) of GSK2292767 | 170.7836 Picograms per milliliter | Geometric Coefficient of Variation 43.7 |
| 200 µg OD | Part A: Maximum Observed Plasma Drug Concentration (Cmax) of GSK2292767 | 356.0719 Picograms per milliliter | Geometric Coefficient of Variation 39.4 |
| 500 µg OD | Part A: Maximum Observed Plasma Drug Concentration (Cmax) of GSK2292767 | 579.8303 Picograms per milliliter | Geometric Coefficient of Variation 39.5 |
| 1000 µg OD | Part A: Maximum Observed Plasma Drug Concentration (Cmax) of GSK2292767 | 1325.3877 Picograms per milliliter | Geometric Coefficient of Variation 44.9 |
90% CI: [0.61, 0.99]
90% CI: [0.75, 1.22]
90% CI: [0.68, 0.97]
90% CI: [0.51, 0.86]
90% CI: [0.63, 0.9]
Secondary
Part A: Terminal Half-life (T1/2) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for T1/2 of GSK2292767 for part A is presented. T1/2 is defined as the time required for one half of the total amount of a particular substance in a biological system to be degraded by biological processes. Only those participants with data available at the specified time points were analyzed.
Time frame: Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 µg OD | Part A: Terminal Half-life (T1/2) of GSK2292767 | 1.6658 Hours | Geometric Coefficient of Variation 32.1 |
| 100 µg OD | Part A: Terminal Half-life (T1/2) of GSK2292767 | 2.3157 Hours | Geometric Coefficient of Variation 16.9 |
| 200 µg OD | Part A: Terminal Half-life (T1/2) of GSK2292767 | 3.9789 Hours | Geometric Coefficient of Variation 57.6 |
| 500 µg OD | Part A: Terminal Half-life (T1/2) of GSK2292767 | 3.1712 Hours | Geometric Coefficient of Variation 30.2 |
| 1000 µg OD | Part A: Terminal Half-life (T1/2) of GSK2292767 | 6.3179 Hours | Geometric Coefficient of Variation 35.8 |
Secondary
Part A: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Tmax of GSK2292767 for part A is presented.
Time frame: Pre-dose (5 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr post dose in each of the 3 treatment periods
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Part A: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK2292767 | 1.0046 Hours |
| 50 µg OD | Part A: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK2292767 | 0.7540 Hours |
| 100 µg OD | Part A: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK2292767 | 0.7500 Hours |
| 200 µg OD | Part A: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK2292767 | 0.7583 Hours |
| 500 µg OD | Part A: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK2292767 | 1.0264 Hours |
| 1000 µg OD | Part A: Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK2292767 | 1.0125 Hours |
Secondary
Part A: Trough Concentrations (Ctau) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Ctau of GSK2292767 for part A is presented. Ctau is defined as the lowest concentration reached by a drug before the next dose is administered.
Time frame: 24 hr post dose in each of the 3 treatment periods
Population: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 µg OD | Part A: Trough Concentrations (Ctau) of GSK2292767 | 43.5566 Picograms per milliliter | Geometric Coefficient of Variation 65.9 |
| 500 µg OD | Part A: Trough Concentrations (Ctau) of GSK2292767 | 44.1985 Picograms per milliliter | Geometric Coefficient of Variation 46.4 |
| 1000 µg OD | Part A: Trough Concentrations (Ctau) of GSK2292767 | 71.6727 Picograms per milliliter | Geometric Coefficient of Variation 55.6 |
Secondary
Part B: AUC (0 to t), AUC (0 to 24) and AUC (0 to Inf) of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for AUC (0 to t), AUC (0 to 24) and AUC (0 to inf) of GSK2292767 for part B is presented. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time frame: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Population: Pharmacokinetic population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part B: AUC (0 to t), AUC (0 to 24) and AUC (0 to Inf) of GSK2292767 | AUC (0-24); Day 1; n=8 | 8163.4986 Hours*picograms per milliliter | Geometric Coefficient of Variation 71.7 |
| Placebo | Part B: AUC (0 to t), AUC (0 to 24) and AUC (0 to Inf) of GSK2292767 | AUC (0-24); Day 14; n=9 | 9941.5681 Hours*picograms per milliliter | Geometric Coefficient of Variation 53.5 |
| Placebo | Part B: AUC (0 to t), AUC (0 to 24) and AUC (0 to Inf) of GSK2292767 | AUC(0-inf); Day 1; n=7 | 10162.0636 Hours*picograms per milliliter | Geometric Coefficient of Variation 66.1 |
| Placebo | Part B: AUC (0 to t), AUC (0 to 24) and AUC (0 to Inf) of GSK2292767 | AUC(0-inf);Day 14; n=7 | 13798.7637 Hours*picograms per milliliter | Geometric Coefficient of Variation 66.7 |
| Placebo | Part B: AUC (0 to t), AUC (0 to 24) and AUC (0 to Inf) of GSK2292767 | AUC (0-t); Day 1; n=9 | 7506.5587 Hours*picograms per milliliter | Geometric Coefficient of Variation 72.3 |
| Placebo | Part B: AUC (0 to t), AUC (0 to 24) and AUC (0 to Inf) of GSK2292767 | AUC (0-t); Day 14; n=9 | 11861.0783 Hours*picograms per milliliter | Geometric Coefficient of Variation 59.5 |
90% CI: [1.01, 1.47]
Secondary
Part B: Cmax of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Five minute post dose concentrations on Days 2-13 were assumed to be the Cmax values. Data for Cmax of GSK2292767 for part B is presented.
Time frame: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part B: Cmax of GSK2292767 | Day 1 | 1145.7369 Picograms per milliliter | Geometric Coefficient of Variation 45.9 |
| Placebo | Part B: Cmax of GSK2292767 | Day 2 | 804.0363 Picograms per milliliter | Geometric Coefficient of Variation 40.9 |
| Placebo | Part B: Cmax of GSK2292767 | Day 3 | 871.6343 Picograms per milliliter | Geometric Coefficient of Variation 38 |
| Placebo | Part B: Cmax of GSK2292767 | Day 4 | 836.4375 Picograms per milliliter | Geometric Coefficient of Variation 36 |
| Placebo | Part B: Cmax of GSK2292767 | Day 5 | 764.7799 Picograms per milliliter | Geometric Coefficient of Variation 35.5 |
| Placebo | Part B: Cmax of GSK2292767 | Day 6 | 785.9632 Picograms per milliliter | Geometric Coefficient of Variation 49 |
| Placebo | Part B: Cmax of GSK2292767 | Day 7 | 877.1960 Picograms per milliliter | Geometric Coefficient of Variation 37.7 |
| Placebo | Part B: Cmax of GSK2292767 | Day 8 | 780.2829 Picograms per milliliter | Geometric Coefficient of Variation 42 |
| Placebo | Part B: Cmax of GSK2292767 | Day 9 | 745.6613 Picograms per milliliter | Geometric Coefficient of Variation 35.2 |
| Placebo | Part B: Cmax of GSK2292767 | Day 10 | 829.2395 Picograms per milliliter | Geometric Coefficient of Variation 41.8 |
| Placebo | Part B: Cmax of GSK2292767 | Day 11 | 952.5536 Picograms per milliliter | Geometric Coefficient of Variation 40.1 |
| Placebo | Part B: Cmax of GSK2292767 | Day 12 | 881.2328 Picograms per milliliter | Geometric Coefficient of Variation 46 |
| Placebo | Part B: Cmax of GSK2292767 | Day 13 | 888.9151 Picograms per milliliter | Geometric Coefficient of Variation 42.9 |
| Placebo | Part B: Cmax of GSK2292767 | Day 14 | 1305.8068 Picograms per milliliter | Geometric Coefficient of Variation 41.9 |
90% CI: [0.96, 1.36]
Secondary
Part B: Concentration of GSK2292767 in Bronchoalveolar Lavage (BAL)
BAL samples were collected by bronchoscopy.
Time frame: Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part B: Concentration of GSK2292767 in Bronchoalveolar Lavage (BAL) | 8852.94 Picograms per milliliter | Geometric Coefficient of Variation 236.8 |
Secondary
Part B: Concentration of GSK2292767 in Lung Epithelial Lining Fluid (ELF)
ELF from the lung was extracted from BAL samples. ELF drug concentration was calculated as BAL fluid drug concentration multiplied by dilution factor where dilution factor = Plasma urea (pre-bronchoscopy) divided by BAL urea. NA indicates data not available. Only participants with data available at specified time points were analyzed (represented by n=X in category titles).
Time frame: Day 15
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part B: Concentration of GSK2292767 in Lung Epithelial Lining Fluid (ELF) | 24 Hr Wash 2,n=8 | 9777.25 Picograms per milliliters | Geometric Coefficient of Variation 290.8 |
| Placebo | Part B: Concentration of GSK2292767 in Lung Epithelial Lining Fluid (ELF) | 24 Hr Wash 3,n=7 | 11921.13 Picograms per milliliters | Geometric Coefficient of Variation 251.4 |
| Unknown | Part B: Concentration of GSK2292767 in Lung Epithelial Lining Fluid (ELF) | 24 Hr Wash 1,n=0 | — Picograms per milliliters | — |
Secondary
Part B: Ctau of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Ctau of GSK2292767 for part B is presented. Ctau is defined as the lowest concentration reached by a drug before the next dose is administered. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time frame: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part B: Ctau of GSK2292767 | Day 9;n=9 | 105.3676 Pico grams per milliliter | Geometric Coefficient of Variation 81.7 |
| Placebo | Part B: Ctau of GSK2292767 | Day 10;n=9 | 117.8348 Pico grams per milliliter | Geometric Coefficient of Variation 80.5 |
| Placebo | Part B: Ctau of GSK2292767 | Day 11;n=9 | 112.3146 Pico grams per milliliter | Geometric Coefficient of Variation 66.4 |
| Placebo | Part B: Ctau of GSK2292767 | Day 12;n=8 | 129.6370 Pico grams per milliliter | Geometric Coefficient of Variation 62.8 |
| Placebo | Part B: Ctau of GSK2292767 | Day 13;n=8 | 154.5480 Pico grams per milliliter | Geometric Coefficient of Variation 52.6 |
| Placebo | Part B: Ctau of GSK2292767 | Day 14;n=9 | 138.2161 Pico grams per milliliter | Geometric Coefficient of Variation 96.7 |
| Placebo | Part B: Ctau of GSK2292767 | Day 1;n=8 | 78.4862 Pico grams per milliliter | Geometric Coefficient of Variation 91.4 |
| Placebo | Part B: Ctau of GSK2292767 | Day 2;n=9 | 103.4247 Pico grams per milliliter | Geometric Coefficient of Variation 83.8 |
| Placebo | Part B: Ctau of GSK2292767 | Day 3;n=9 | 98.3515 Pico grams per milliliter | Geometric Coefficient of Variation 84.1 |
| Placebo | Part B: Ctau of GSK2292767 | Day 4;n=9 | 112.5132 Pico grams per milliliter | Geometric Coefficient of Variation 83.4 |
| Placebo | Part B: Ctau of GSK2292767 | Day 5;n=9 | 98.4430 Pico grams per milliliter | Geometric Coefficient of Variation 87.6 |
| Placebo | Part B: Ctau of GSK2292767 | Day 6;n=9 | 106.6896 Pico grams per milliliter | Geometric Coefficient of Variation 96.2 |
| Placebo | Part B: Ctau of GSK2292767 | Day 7;n=9 | 101.1219 Pico grams per milliliter | Geometric Coefficient of Variation 88.3 |
| Placebo | Part B: Ctau of GSK2292767 | Day 8;n=8 | 116.9160 Pico grams per milliliter | Geometric Coefficient of Variation 62.4 |
90% CI: [1.67, 2.55]
Secondary
Part B: T1/2 of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for T1/2 of GSK2292767 for part B is presented. T1/2 was defined as the time required for one half of the total amount of a particular substance in a biological system to be degraded by biological processes. Only those participants with data available at the specified time points were analyzed.
Time frame: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Part B: T1/2 of GSK2292767 | Day 1 | 6.4625 Hours | Geometric Coefficient of Variation 35 |
| Placebo | Part B: T1/2 of GSK2292767 | Day 14 | 11.7665 Hours | Geometric Coefficient of Variation 48.6 |
Secondary
Part B: Tmax of GSK2292767
Blood samples were collected for pharmacokinetic analysis of GSK2292767 at the specified time points. Data for Tmax of GSK2292767 for part B is presented.
Time frame: Pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 1; pre-dose, 5 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8 and 12hours post dose on Day 14
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Part B: Tmax of GSK2292767 | Day 1 | 1.0056 Hours |
| Placebo | Part B: Tmax of GSK2292767 | Day 14 | 1.0050 Hours |