Activated PI3K-delta Syndrome
Conditions
Keywords
APDS, Safety, Pharmacokinetics, GSK2269557, PASLI
Brief summary
This is an open-label study conducted to investigate safety, pharmacokinetics and pharmacodynamics of repeat doses of inhaled nemiralisib (NEMI) in participants with activated phosphoinositide 3-kinase (PI3K) delta syndrome /p110 delta-activating mutation causing senescent T Cells, lymphadenopathy and immunodeficiency (APDS/PASLI)
Interventions
DRUGNemiralisib
Participants will be administered nemiralisib
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects aged 18 or older at the time of signing the informed consent. * Patients with a clinical phenotype consistent with APDS, including a history of recurrent (frequency greater than would be expected in an immunocompetent individual) ear, sinus or pulmonary infections, and who have a known type 1 APDS-associated genetic PI3K delta mutation (i.e. E1021K, N334K, E525K and C416R). * Body weight \>=45 kilograms (kg) and body mass index (BMI) \>=18 kg/square meter (m\^2) (inclusive) * Male subject. Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until completion of the follow-up telephone call at 1-2 weeks from last dose. Vasectomy with documentation of azoospermia. Male condom plus partner use of one of the following contraceptive options: 1. Contraceptive subdermal implant 2. Intrauterine device or intrauterine system 3. Combined estrogen and progestogen oral contraceptive, 4. Injectable progestogen 5. Contraceptive vaginal ring 6. Percutaneous contraceptive patches. This is an all inclusive list of those methods that meet the GSK definition of highly effective: having a failure rate of less than 1% per year when used consistently and, correctly and, when applicable, in accordance with the product label. For non-product methods (e.g. male sterility), the investigator determines what is consistent and correct use. The GlaxoSmithKline (GSK) definition is based on the definition provided by International Conference on Harmonisation (ICH). * Female subject. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies: 1. Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. 2. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until completion of the follow-up telephone call at 1-2 weeks from last dose. * Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
Exclusion criteria
* Alanine aminotransferase (ALT) \>2xupper limit normal (ULN) and bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Current or chronic history of liver disease except where hepatomegaly is identified by their clinician to be secondary to APDS, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Corrected QT interval (QTc) \> 450 milliseconds (msec) or QTc \> 480 msec in subjects with Bundle Branch Block * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline (Day 1: pre-dose) and at Day 1: 1 Hour post-dose; Day 2: 1 Hour post-dose; Day 14: Pre-dose; Day 14: 1 Hour post-dose and Day 83: Pre-dose | FEV1 is used to assess pulmonary function using a spirometer at indicated timepoints. Baseline value is defined as the maximum measurement of the planned pre-dose measurements on Day 1, predose. Change from Baseline is defined as post-dose visit value minus Baseline value. Spirometry assessments were performed in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines |
| Number of Participants With Any Serious Adverse Events (SAEs) and Any Non-serious Adverse Events (Non-SAEs) | Upto 7.5 months | An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as judged by physician. Number of participants with any SAE and non-SAEs are presented. |
| Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84 | SBP and DBP were measured in participants in a semi-supine position after 5 minutes rest. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Not applicable (NA) indicates that standard deviation could not be calculated as a single participant was analyzed. |
| Change From Baseline in Pulse Rate | Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84 | Pulse rate was measured in participants in a semi-supine position after 5 minutes rest. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. NA indicates that standard deviation could not be calculated as a single participant was analyzed. |
| Change From Baseline in Respiratory Rate | Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84 | Respiratory rate was measured in participants in a semi-supine position after 5 minutes rest. . Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. NA indicates that standard deviation could not be calculated as a single participant was analyzed. |
| Change From Baseline in Body Temperature | Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84 | Temperature was measured in participants in a semi-supine position after 5 minutes rest. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. NA indicates that standard deviation could not be calculated as a single participant was analyzed. |
| Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate | Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83 | Single 12-lead ECGs were recorded at indicated timepoints using an ECG machine that automatically calculated the heart rate. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83 | Twelve lead ECGs were recorded at indicated timepoints. At each time point, ECG machine automatically measured QRS duration, uncorrected QT interval, QTcF interval and QTcB. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | Baseline (Day -1) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of clinical parameters including ALT, ALP and AST. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein | Baseline (Day -1) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of clinical chemistry parameter-albumin and total protein. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Baseline (Day -1) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of clinical parameters including sodium, potassium, calcium, glucose and urea. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Baseline (Day -1) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of clinical chemistry parameters: direct bilirubin, total bilirubin and creatinine. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline Values in Clinical Chemistry Parameter: C-Reactive Protein | Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of clinical chemistry parameter:C-Reactive Protein. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Baseline (Day -1) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, WBC, lymphocytes, neutrophils, monocytes and platelets at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline for Hematology Parameter: Hemoglobin | Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of hematology parameter: hemoglobin at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline for Hematology Parameter: Hematocrit | Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of hematology parameter: hematocrit at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV) | Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of hematology parameter: MCV at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) | Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of hematology parameters including MCH at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Change From Baseline for Hematology Parameter: Red Blood Cell Count | Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83 | Blood samples were collected for the analysis of hematology parameter: Blood Cell Count at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration Following Administration of NEMI | Day 1: Pre-dose, 5 minutes, 3 hours and 24 hours post-dose; Days 14 and 83: pre-dose | Blood samples for pharmacokinetic analysis was collected at the indicated time points following administration of NEMI. NA indicates that standard deviation could not be calculated as a single participant was analyzed |
Countries
United Kingdom
Participant flow
Recruitment details
This is an open-label study conducted to investigate safety, pharmacokinetics and pharmacodynamics of repeat doses of inhaled nemiralisib (NEMI) in participants with activated phosphoinositide 3-kinase (PI3K) delta syndrome /p110 delta-activating mutation causing senescent T Cells, lymphadenopathy and immunodeficiency (APDS/PASLI)
Pre-assignment details
Participants received either 1000 mcg NEMI DISKUS or 700 mcg NEMI ELLIPTA or 500 mcg NEMI ELLIPTA. All NEMI DISKUS and NEMI ELLIPTA dose levels were combined as All NEMI treatment group as there was no intent to compare two dose levels or devices. The study had protocol amendments to reflect changes in dose and device administration.
Participants by arm
| Arm | Count |
|---|---|
| All NEMI Participants were administered with either NEMI 1000 mcg using DISKUS DPI or NEMI 700 or 500 mcg using ELLIPTA DPI once daily in the morning. NEMI DISKUS and NEMI ELLIPTA were combined as All NEMI treatment group as there was no intent to compare two dose levels or devices. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | All NEMI |
|---|---|
| Age, Continuous | 36.6 Years STANDARD_DEVIATION 12.36 |
| Race/Ethnicity, Customized White-White/Caucasian/European Heritage | 5 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Change From Baseline for Hematology Parameter: Hematocrit
Blood samples were collected for the analysis of hematology parameter: hematocrit at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline for Hematology Parameter: Hematocrit | Day 14, n= 5 | 0.0320 Percentage of red blood cells in blood | Standard Deviation 0.01488 |
| All NEMI | Change From Baseline for Hematology Parameter: Hematocrit | Day 28, n= 4 | 0.0333 Percentage of red blood cells in blood | Standard Deviation 0.01204 |
| All NEMI | Change From Baseline for Hematology Parameter: Hematocrit | Day 56, n= 4 | 0.0518 Percentage of red blood cells in blood | Standard Deviation 0.02337 |
| All NEMI | Change From Baseline for Hematology Parameter: Hematocrit | Day 83, n= 4 | 0.0465 Percentage of red blood cells in blood | Standard Deviation 0.01396 |
Primary
Change From Baseline for Hematology Parameter: Hemoglobin
Blood samples were collected for the analysis of hematology parameter: hemoglobin at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline for Hematology Parameter: Hemoglobin | Day 14, n= 5 | 10.0 Grams per liter | Standard Deviation 5.24 |
| All NEMI | Change From Baseline for Hematology Parameter: Hemoglobin | Day 28, n= 4 | 8.3 Grams per liter | Standard Deviation 3.77 |
| All NEMI | Change From Baseline for Hematology Parameter: Hemoglobin | Day 56, n= 4 | 13.5 Grams per liter | Standard Deviation 8.5 |
| All NEMI | Change From Baseline for Hematology Parameter: Hemoglobin | Day 83, n= 4 | 13.3 Grams per liter | Standard Deviation 5.74 |
Primary
Change From Baseline for Hematology Parameter: Red Blood Cell Count
Blood samples were collected for the analysis of hematology parameter: Blood Cell Count at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline for Hematology Parameter: Red Blood Cell Count | Day 14, n= 5 | 0.304 10^12 cells per liter | Standard Deviation 0.1417 |
| All NEMI | Change From Baseline for Hematology Parameter: Red Blood Cell Count | Day 28, n= 4 | 0.280 10^12 cells per liter | Standard Deviation 0.0673 |
| All NEMI | Change From Baseline for Hematology Parameter: Red Blood Cell Count | Day 56, n= 4 | 0.488 10^12 cells per liter | Standard Deviation 0.164 |
| All NEMI | Change From Baseline for Hematology Parameter: Red Blood Cell Count | Day 83, n= 4 | 0.485 10^12 cells per liter | Standard Deviation 0.1034 |
Primary
Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets
Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, WBC, lymphocytes, neutrophils, monocytes and platelets at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Basophils, Day 14, n= 5 | -0.002 10^9 cells per liters | Standard Deviation 0.0045 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Basophils, Day 28, n= 4 | 0.008 10^9 cells per liters | Standard Deviation 0.0096 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Basophils, Day 56, n= 4 | 0.008 10^9 cells per liters | Standard Deviation 0.0236 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Basophils, Day 83, n= 4 | 0.013 10^9 cells per liters | Standard Deviation 0.0222 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Eosinophils, Day 14, n= 5 | 0.108 10^9 cells per liters | Standard Deviation 0.1542 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Eosinophils, Day 28, n= 4 | 0.088 10^9 cells per liters | Standard Deviation 0.065 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Eosinophils, Day 56, n= 4 | 0.128 10^9 cells per liters | Standard Deviation 0.2241 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Eosinophils, Day 83, n= 4 | 0.075 10^9 cells per liters | Standard Deviation 0.081 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Lymphocytes, Day 14, n= 5 | 0.122 10^9 cells per liters | Standard Deviation 0.2411 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Lymphocytes, Day 28, n= 4 | -0.133 10^9 cells per liters | Standard Deviation 0.0918 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Lymphocytes, Day 56, n= 4 | -0.105 10^9 cells per liters | Standard Deviation 0.1115 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Lymphocytes, Day 83, n= 4 | 0.037 10^9 cells per liters | Standard Deviation 0.314 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Monocytes, Day 14, n= 5 | 0.096 10^9 cells per liters | Standard Deviation 0.2893 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Monocytes, Day 28, n= 4 | 0.030 10^9 cells per liters | Standard Deviation 0.0572 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Monocytes, Day 56, n= 4 | 0.115 10^9 cells per liters | Standard Deviation 0.0614 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Monocytes, Day 83, n= 4 | 0.065 10^9 cells per liters | Standard Deviation 0.0592 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Neutrophils , Day 14, n= 5 | 0.334 10^9 cells per liters | Standard Deviation 1.2388 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Neutrophils , Day 28, n= 4 | 0.575 10^9 cells per liters | Standard Deviation 0.6125 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Neutrophils , Day 56, n= 4 | 0.553 10^9 cells per liters | Standard Deviation 0.7647 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Neutrophils , Day 83, n= 4 | 0.653 10^9 cells per liters | Standard Deviation 0.7857 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Platelet, Day 14, n= 5 | 49.4 10^9 cells per liters | Standard Deviation 52.53 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Platelet, Day 28, n= 4 | 9.0 10^9 cells per liters | Standard Deviation 25.86 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Platelet, Day 56, n= 4 | 17.0 10^9 cells per liters | Standard Deviation 31.79 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | Platelet, Day 83, n= 4 | 61.8 10^9 cells per liters | Standard Deviation 43.41 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | WBC, Day 14, n= 5 | 0.656 10^9 cells per liters | Standard Deviation 1.0304 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | WBC, Day 28, n= 4 | 0.568 10^9 cells per liters | Standard Deviation 0.6004 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | WBC, Day 56, n= 4 | 0.698 10^9 cells per liters | Standard Deviation 1.0605 |
| All NEMI | Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets | WBC, Day 83, n= 4 | 0.845 10^9 cells per liters | Standard Deviation 0.6608 |
Primary
Change From Baseline in Body Temperature
Temperature was measured in participants in a semi-supine position after 5 minutes rest. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. NA indicates that standard deviation could not be calculated as a single participant was analyzed.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in Body Temperature | Day 14, n= 5 | 0.10 Degrees celsius | Standard Deviation 0.158 |
| All NEMI | Change From Baseline in Body Temperature | Day 28, n= 4 | 0.17 Degrees celsius | Standard Deviation 0.35 |
| All NEMI | Change From Baseline in Body Temperature | Day 56, n= 4 | 0.07 Degrees celsius | Standard Deviation 0.171 |
| All NEMI | Change From Baseline in Body Temperature | Day 83, n= 4 | 0.17 Degrees celsius | Standard Deviation 0.479 |
| All NEMI | Change From Baseline in Body Temperature | Day 84 n= 1 | 0.50 Degrees celsius | — |
Primary
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)
Blood samples were collected for the analysis of clinical parameters including ALT, ALP and AST. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | ALT, Day 14, n= 5 | 1.0 International units per liter (IU/L) | Standard Deviation 2.12 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | ALT, Day 28, n= 4 | 0.8 International units per liter (IU/L) | Standard Deviation 1.71 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | ALT, Day 56, n= 4 | 0.0 International units per liter (IU/L) | Standard Deviation 1.63 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | ALT, Day 83, n= 4 | 1.3 International units per liter (IU/L) | Standard Deviation 7.5 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | AST, Day 14, n= 5 | -0.8 International units per liter (IU/L) | Standard Deviation 1.48 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | AST, Day 28, n= 4 | 0.8 International units per liter (IU/L) | Standard Deviation 2.22 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | AST, Day 56, n= 4 | -0.8 International units per liter (IU/L) | Standard Deviation 4.79 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | AST, Day 83, n= 4 | -1.0 International units per liter (IU/L) | Standard Deviation 7.7 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | ALP, Day 14, n= 5 | 2.6 International units per liter (IU/L) | Standard Deviation 5.77 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | ALP, Day 28, n= 4 | 3.8 International units per liter (IU/L) | Standard Deviation 5.68 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | ALP, Day 56, n= 4 | 7.5 International units per liter (IU/L) | Standard Deviation 5 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) | ALP, Day 83, n= 4 | 6.0 International units per liter (IU/L) | Standard Deviation 2.94 |
Primary
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein
Blood samples were collected for the analysis of clinical chemistry parameter-albumin and total protein. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein | Albumin, Day 14, n= 5 | 2.6 Grams per liter | Standard Deviation 2.07 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein | Albumin, Day 28, n= 4 | 1.3 Grams per liter | Standard Deviation 3.2 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein | Albumin, Day 56, n= 4 | 2.8 Grams per liter | Standard Deviation 2.36 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein | Albumin, Day 83, n= 4 | 2.0 Grams per liter | Standard Deviation 3.16 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein | Total Protein, Day 14, n= 5 | 4.0 Grams per liter | Standard Deviation 1.58 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein | Total Protein, Day 28, n= 4 | 1.3 Grams per liter | Standard Deviation 3.59 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein | Total Protein, Day 56, n= 4 | 4.0 Grams per liter | Standard Deviation 4.76 |
| All NEMI | Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein | Total Protein, Day 83, n= 4 | 4.3 Grams per liter | Standard Deviation 2.5 |
Primary
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP and DBP were measured in participants in a semi-supine position after 5 minutes rest. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Not applicable (NA) indicates that standard deviation could not be calculated as a single participant was analyzed.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, Day 14, n= 5 | 1.0 Millimeters of Mercury (mmHg) | Standard Deviation 6.44 |
| All NEMI | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, Day 28, n= 4 | 4.0 Millimeters of Mercury (mmHg) | Standard Deviation 6.98 |
| All NEMI | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, Day 56, n= 4 | 8.5 Millimeters of Mercury (mmHg) | Standard Deviation 5.8 |
| All NEMI | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, Day 83, n= 4 | 2.0 Millimeters of Mercury (mmHg) | Standard Deviation 4.4 |
| All NEMI | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, Day 84 n= 1 | 17.0 Millimeters of Mercury (mmHg) | — |
| All NEMI | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, Day 14, n= 5 | -1.0 Millimeters of Mercury (mmHg) | Standard Deviation 3.67 |
| All NEMI | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, Day 28, n= 4 | 5.3 Millimeters of Mercury (mmHg) | Standard Deviation 8.54 |
| All NEMI | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, Day 56, n= 4 | 10.0 Millimeters of Mercury (mmHg) | Standard Deviation 9.31 |
| All NEMI | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, Day 83, n= 4 | 1.5 Millimeters of Mercury (mmHg) | Standard Deviation 3.51 |
| All NEMI | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, Day 84, n= 1 | 16.0 Millimeters of Mercury (mmHg) | — |
Primary
Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate
Single 12-lead ECGs were recorded at indicated timepoints using an ECG machine that automatically calculated the heart rate. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate | Day 14, n= 5 | -1.0 Beats per minute | Standard Deviation 3.94 |
| All NEMI | Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate | Day 28, n= 4 | -0.8 Beats per minute | Standard Deviation 2.99 |
| All NEMI | Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate | Day 56, n= 4 | 5.3 Beats per minute | Standard Deviation 7.54 |
| All NEMI | Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate | Day 83, n= 4 | 1.0 Beats per minute | Standard Deviation 2.31 |
Primary
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
FEV1 is used to assess pulmonary function using a spirometer at indicated timepoints. Baseline value is defined as the maximum measurement of the planned pre-dose measurements on Day 1, predose. Change from Baseline is defined as post-dose visit value minus Baseline value. Spirometry assessments were performed in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines
Time frame: Baseline (Day 1: pre-dose) and at Day 1: 1 Hour post-dose; Day 2: 1 Hour post-dose; Day 14: Pre-dose; Day 14: 1 Hour post-dose and Day 83: Pre-dose
Population: All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 1, 1 Hour post-dose | 0.226 Liters | Standard Deviation 0.2166 |
| All NEMI | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 2, 1 Hour post-dose | 0.290 Liters | Standard Deviation 0.2884 |
| All NEMI | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 14, Pre-dose | -0.165 Liters | Standard Deviation 0.5024 |
| All NEMI | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 14, 1 Hour post-dose | 0.016 Liters | Standard Deviation 0.4812 |
| All NEMI | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 83, Pre-dose | -0.002 Liters | Standard Deviation 0.4584 |
Primary
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected for the analysis of hematology parameters including MCH at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) | Day 14, n= 5 | 0.10 Picograms | Standard Deviation 0.485 |
| All NEMI | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) | Day 28, n= 4 | -0.15 Picograms | Standard Deviation 0.676 |
| All NEMI | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) | Day 56, n= 4 | -0.43 Picograms | Standard Deviation 0.763 |
| All NEMI | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) | Day 83, n= 4 | -0.47 Picograms | Standard Deviation 0.525 |
Primary
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)
Blood samples were collected for the analysis of hematology parameter: MCV at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV) | Day 14, n= 5 | 1.00 Femtoliters | Standard Deviation 2.187 |
| All NEMI | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV) | Day 28, n= 4 | 2.33 Femtoliters | Standard Deviation 2.287 |
| All NEMI | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV) | Day 56, n= 4 | 2.02 Femtoliters | Standard Deviation 2.331 |
| All NEMI | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV) | Day 83, n= 4 | 1.03 Femtoliters | Standard Deviation 3.407 |
Primary
Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB)
Twelve lead ECGs were recorded at indicated timepoints. At each time point, ECG machine automatically measured QRS duration, uncorrected QT interval, QTcF interval and QTcB. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | PR, Day 14, n= 5 | -2.2 Milliseconds | Standard Deviation 9.23 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | PR, Day 28, n= 4 | -4.8 Milliseconds | Standard Deviation 4.27 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | PR, Day 56, n= 4 | -3.3 Milliseconds | Standard Deviation 11.18 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | PR, Day 83, n= 4 | -6.0 Milliseconds | Standard Deviation 11.8 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QRS Duration, Day 14, n= 5 | -5.6 Milliseconds | Standard Deviation 7.33 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QRS Duration, Day 28, n= 4 | -4.5 Milliseconds | Standard Deviation 11.03 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QRS Duration, Day 56, n= 4 | -6.5 Milliseconds | Standard Deviation 8.81 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QRS Duration, Day 83, n= 4 | -6.0 Milliseconds | Standard Deviation 7.79 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QT Interval, Day 14, n= 5 | -7.2 Milliseconds | Standard Deviation 10.66 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QT Interval, Day 28, n= 4 | -2.8 Milliseconds | Standard Deviation 28.89 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QT Interval, Day 56, n= 4 | -22.3 Milliseconds | Standard Deviation 16.01 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QT Interval, Day 83, n= 4 | -16.3 Milliseconds | Standard Deviation 9.74 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QTcB, Day 14, n= 5 | -9.4 Milliseconds | Standard Deviation 4.93 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QTcB, Day 28, n= 4 | -4.5 Milliseconds | Standard Deviation 22.55 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QTcB, Day 56, n= 4 | -8.3 Milliseconds | Standard Deviation 24.55 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QTcB, Day 83, n= 4 | -12.5 Milliseconds | Standard Deviation 8.19 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QTcF, Day 14, n= 5 | -8.2 Milliseconds | Standard Deviation 4.32 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QTcF, Day 28, n= 4 | -3.5 Milliseconds | Standard Deviation 24.09 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QTcF, Day 56, n= 4 | -13.0 Milliseconds | Standard Deviation 19.92 |
| All NEMI | Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB) | QTcF, Day 83, n= 4 | -14.0 Milliseconds | Standard Deviation 7.79 |
Primary
Change From Baseline in Pulse Rate
Pulse rate was measured in participants in a semi-supine position after 5 minutes rest. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. NA indicates that standard deviation could not be calculated as a single participant was analyzed.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in Pulse Rate | Day 14, n= 5 | 3.2 Beats per minute | Standard Deviation 7.73 |
| All NEMI | Change From Baseline in Pulse Rate | Day 28, n= 4 | 2.0 Beats per minute | Standard Deviation 10.86 |
| All NEMI | Change From Baseline in Pulse Rate | Day 56, n= 4 | 6.8 Beats per minute | Standard Deviation 9.43 |
| All NEMI | Change From Baseline in Pulse Rate | Day 83, n= 4 | 4.8 Beats per minute | Standard Deviation 7.76 |
| All NEMI | Change From Baseline in Pulse Rate | Day 84 n= 1 | 7.0 Beats per minute | — |
Primary
Change From Baseline in Respiratory Rate
Respiratory rate was measured in participants in a semi-supine position after 5 minutes rest. . Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. NA indicates that standard deviation could not be calculated as a single participant was analyzed.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline in Respiratory Rate | Day 14, n= 5 | 0.2 Breaths per minute | Standard Deviation 2.28 |
| All NEMI | Change From Baseline in Respiratory Rate | Day 28, n= 4 | 0.8 Breaths per minute | Standard Deviation 4.57 |
| All NEMI | Change From Baseline in Respiratory Rate | Day 56, n= 4 | 1.5 Breaths per minute | Standard Deviation 5.26 |
| All NEMI | Change From Baseline in Respiratory Rate | Day 83, n= 4 | 1.0 Breaths per minute | Standard Deviation 2.45 |
| All NEMI | Change From Baseline in Respiratory Rate | Day 84 n= 1 | 2.0 Breaths per minute | — |
Primary
Change From Baseline Values in Clinical Chemistry Parameter: C-Reactive Protein
Blood samples were collected for the analysis of clinical chemistry parameter:C-Reactive Protein. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameter: C-Reactive Protein | Day 14, n= 5 | 0.56 Milligrams per liter | Standard Deviation 1.592 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameter: C-Reactive Protein | Day 28, n= 4 | 0.75 Milligrams per liter | Standard Deviation 1.085 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameter: C-Reactive Protein | Day 56, n= 4 | 2.75 Milligrams per liter | Standard Deviation 6.222 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameter: C-Reactive Protein | Day 83, n= 4 | 3.90 Milligrams per liter | Standard Deviation 7.141 |
Primary
Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Blood samples were collected for the analysis of clinical chemistry parameters: direct bilirubin, total bilirubin and creatinine. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Creatinine , Day 56, n= 4 | 5.0 Micromoles per liter | Standard Deviation 14.07 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Direct bilirubin, Day 14, n= 5 | -1.0 Micromoles per liter | Standard Deviation 0.71 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Direct bilirubin, Day 28, n= 4 | -1.8 Micromoles per liter | Standard Deviation 0.96 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Direct bilirubin, Day 56, n= 4 | -0.5 Micromoles per liter | Standard Deviation 1 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Direct bilirubin, Day 83, n= 4 | -0.5 Micromoles per liter | Standard Deviation 1 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Total bilirubin, Day 14, n= 5 | -1.8 Micromoles per liter | Standard Deviation 1.64 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Total bilirubin, Day 28, n= 4 | -3.0 Micromoles per liter | Standard Deviation 2.45 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Total bilirubin, Day 56, n= 4 | -0.8 Micromoles per liter | Standard Deviation 1.89 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Total bilirubin, Day 83, n= 4 | -1.5 Micromoles per liter | Standard Deviation 2.52 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Creatinine , Day 14, n= 5 | -2.0 Micromoles per liter | Standard Deviation 12.43 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Creatinine , Day 28, n= 4 | -4.3 Micromoles per liter | Standard Deviation 6.08 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Creatinine , Day 83, n= 4 | -2.5 Micromoles per liter | Standard Deviation 14.93 |
Primary
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea
Blood samples were collected for the analysis of clinical parameters including sodium, potassium, calcium, glucose and urea. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day -1) and at Days 14, 28, 56 and 83
Population: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Urea, Day 83, n= 4 | 2.185 Millimoles per liter | Standard Deviation 4.1025 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Sodium, Day 14, n= 5 | -0.2 Millimoles per liter | Standard Deviation 2.68 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Sodium, Day 28, n= 4 | 0.5 Millimoles per liter | Standard Deviation 0.58 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Sodium, Day 56, n= 4 | -0.8 Millimoles per liter | Standard Deviation 2.06 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Sodium, Day 83, n= 4 | 0.0 Millimoles per liter | Standard Deviation 1.83 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Potassium, Day 14, n= 5 | 0.24 Millimoles per liter | Standard Deviation 0.397 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Potassium, Day 28, n= 4 | 0.30 Millimoles per liter | Standard Deviation 0.346 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Potassium, Day 56, n= 4 | 0.35 Millimoles per liter | Standard Deviation 0.37 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Potassium, Day 83, n= 4 | 0.38 Millimoles per liter | Standard Deviation 0.275 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Calcium, Day 14, n= 5 | 0.040 Millimoles per liter | Standard Deviation 0.099 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Calcium, Day 28, n= 4 | 0.063 Millimoles per liter | Standard Deviation 0.0704 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Calcium, Day 56, n= 4 | 0.133 Millimoles per liter | Standard Deviation 0.1343 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Calcium, Day 83, n= 4 | 0.082 Millimoles per liter | Standard Deviation 0.1325 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Glucose, Day 14, n= 5 | -0.64 Millimoles per liter | Standard Deviation 1.557 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Glucose, Day 28, n= 4 | -0.60 Millimoles per liter | Standard Deviation 1.774 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Glucose, Day 56, n= 4 | -0.48 Millimoles per liter | Standard Deviation 1.578 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Glucose, Day 83, n= 4 | -0.68 Millimoles per liter | Standard Deviation 1.333 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Urea, Day 14, n= 5 | 4.732 Millimoles per liter | Standard Deviation 5.8283 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Urea, Day 28, n= 4 | 8.330 Millimoles per liter | Standard Deviation 2.6837 |
| All NEMI | Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea | Urea, Day 56, n= 4 | 2.610 Millimoles per liter | Standard Deviation 5.1954 |
Primary
Number of Participants With Any Serious Adverse Events (SAEs) and Any Non-serious Adverse Events (Non-SAEs)
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as judged by physician. Number of participants with any SAE and non-SAEs are presented.
Time frame: Upto 7.5 months
Population: All Subjects Population consisted of all participants who received at least one dose of the study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All NEMI | Number of Participants With Any Serious Adverse Events (SAEs) and Any Non-serious Adverse Events (Non-SAEs) | Any non-SAE | 5 Participants |
| All NEMI | Number of Participants With Any Serious Adverse Events (SAEs) and Any Non-serious Adverse Events (Non-SAEs) | Any SAE | 0 Participants |
Secondary
Plasma Concentration Following Administration of NEMI
Blood samples for pharmacokinetic analysis was collected at the indicated time points following administration of NEMI. NA indicates that standard deviation could not be calculated as a single participant was analyzed
Time frame: Day 1: Pre-dose, 5 minutes, 3 hours and 24 hours post-dose; Days 14 and 83: pre-dose
Population: Pharmacokinetic (PK) Population consisted of all participants in the 'All Subjects' population who had at least 1 non-missing PK assessment. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All NEMI | Plasma Concentration Following Administration of NEMI | Day 1: Pre-dose; n=1,1,3 | 0.00 Picograms per milliliter | — |
| All NEMI | Plasma Concentration Following Administration of NEMI | Day 14: Pre-dose; n=1,1,3 | 1396.70 Picograms per milliliter | — |
| All NEMI | Plasma Concentration Following Administration of NEMI | Day 1: 3 hours post-dose; n=1,1,3 | 895.10 Picograms per milliliter | — |
| All NEMI | Plasma Concentration Following Administration of NEMI | Day 1: 24 hours post-dose; n=1,1,3 | 444.40 Picograms per milliliter | — |
| All NEMI | Plasma Concentration Following Administration of NEMI | Day 1: 5 minutes post-dose; n=1,1,3 | 467.00 Picograms per milliliter | — |
| NEMI 700 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 1: 3 hours post-dose; n=1,1,3 | 568.60 Picograms per milliliter | — |
| NEMI 700 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 1: Pre-dose; n=1,1,3 | 0.00 Picograms per milliliter | — |
| NEMI 700 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 1: 5 minutes post-dose; n=1,1,3 | 1524.70 Picograms per milliliter | — |
| NEMI 700 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 1: 24 hours post-dose; n=1,1,3 | 304.90 Picograms per milliliter | — |
| NEMI 700 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 14: Pre-dose; n=1,1,3 | 1242.60 Picograms per milliliter | — |
| NEMI 700 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 83: Pre-dose; n=0,1,3 | 1419.60 Picograms per milliliter | — |
| NEMI 500 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 14: Pre-dose; n=1,1,3 | 750.83 Picograms per milliliter | Standard Deviation 526.337 |
| NEMI 500 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 1: 24 hours post-dose; n=1,1,3 | 198.17 Picograms per milliliter | Standard Deviation 82.442 |
| NEMI 500 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 83: Pre-dose; n=0,1,3 | 1525.83 Picograms per milliliter | Standard Deviation 1181.34 |
| NEMI 500 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 1: 5 minutes post-dose; n=1,1,3 | 658.27 Picograms per milliliter | Standard Deviation 394.468 |
| NEMI 500 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 1: 3 hours post-dose; n=1,1,3 | 397.07 Picograms per milliliter | Standard Deviation 172.226 |
| NEMI 500 mcg Via ELLIPTA | Plasma Concentration Following Administration of NEMI | Day 1: Pre-dose; n=1,1,3 | 0.00 Picograms per milliliter | Standard Deviation 0 |