Asthma
Conditions
Keywords
Asthma, Asthma control questionnaire
Brief summary
Treatment, Randomised, Double Blind, Parallel Assignment, Safety/efficacy Study
Detailed description
A Multi-Centre, Multi-country, Randomized, Double-Blind (Subject, Investigator), Placebo-Controlled, Repeat-Dose study to evaluate the Efficacy and Safety of Intravenous GSK679586 in Patients with Severe Asthma
Interventions
DRUGINTRAVENOUS GSK679586
GSK679586 will be provided as a clear or colorless to pale yellow liquid with the unit dose strength of 10mg/kg and will be infused over an hour. The infusion will be delivered by a programmable infusion pump
DRUGINTRAVENOUS PLACEBO
Clear or colorless 0.9% sodium chloride saline solution will be infused over an hour. The infusion will be delivered by a programmable infusion pump
DRUGFLUTICASONE PROPIONATE
Subjects will be supplied fluticasone propionate at Screening, Run-in and when needed during the study. Subjects will be up-titrated to 1000 μg/day and those who were already taking greater than equal to 1000 μg/day fluticasone propionate or equivalent prior to the study will remain on their pre-study dose.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* history of asthma for ≥ 6 months * taking inhaled corticosteroids * non-smoking * Baseline (pre-bronchodilator) FEV1 35-80% predicted at screening. * Reversible airways disease as indicated by an increase of FEV1 ≥12% from baseline after nebulised salbutamol or albuterol. * symptomatic according to the ACQ-7
Exclusion criteria
* Unstable severe asthma * Recent respiratory illness * Presence of other respiratory disease or chronic pulmonary condition other than asthma * Treatment with omalizumab within 4 months of study * Recent gastrointestinal or respiratory parasitic infestation * History of severe allergy to food or drugs Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Asthma Control Questionnaire (ACQ-7) Over 12 Weeks | Baseline to Week 12 | The ACQ-7 consists of 7 questions scored between zero (no impairment/ limitation) to 6 (total impairment/ limitation). The values of Week 1 is considered as Baseline. ACQ-7 was calculated as the average of the 7 scores. If any one individual score was missing, the ACQ-7 was set to missing.The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Demonstrated a Clinically Meaningful Change in ACQ-7 Over the 12 Weeks Assessment Period. | Upto 12 weeks | The ACQ-7 is a 7-item questionnaire that provides a measure of a participant's asthma control. Participant responses were recorded on a 7-point scale ranging from zero (no impairment/ limitation) to 6 (total impairment/ limitation). The percentage of participants who were classified as responders for ACQ-7, defined as a clinically meaningful decrease from baseline in ACQ-7 of at least 0.50, was generally similar between treatment groups at each visit and over the 12-week treatment period. |
| Change From Baseline in Forced Expiratory Volume (FEV1) Over 12 Weeks. | Baseline to Week 12 | FEV1 is forced expiratory volume in 1 second.Change from Baseline FEV1 was calculated for each of the following visit: Visit 6, Visit 7, Visit 9 and Visit 11. A binary variable was created for each participant with 1 for the responder and 0 for the non nonresponder at each visit. Week 1 was considered as the Baseline. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. |
| Change From Baseline in FEV1 Over 16 Weeks and 24 Weeks | Week 16 and 24 | FEV1 is forced expiratory volume in 1 second.Change from Baseline FEV1 was calculated for each of the following visit: Visit 6, Visit 7, Visit 9 and Visit 11. A binary variable was created for each participant with 1 for the responder and 0 for the non nonresponder at each visit. Week 1 was considered as the Baseline. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. Change from Baseline of Week 16 and Week 24 are incorporated here which are Follow up weeks. |
| Percentage of Participants Who Demonstrated a Clinically Meaningful Increase in FEV1 Over the 12 Week Assessment Period | Upto 12 weeks | FEV1 is forced expiratory volume in 1 second.A participant is defined as a FEV1 responder if he/she achieves a change from baseline FEV1 of \>=200ml. To evaluate whether the participant was a responder over 12 weeks, change from baseline FEV1 over 12 weeks was calculated by taking the mean of the changes at Visit 7, Visit 9 and Visit 11. A binary variable was created for each participant with 1 for the responder and 0 for the non-responder. If either Visit 9 or Visit 11 FEV1 data are missing, then the binary variable for the responder over 12 weeks was set to be missing. If Visit 7 data were missing, but Visit 9 and Visit 11 data were available, then the binary variable for the responder over 12 weeks was still calculated. |
| Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Week 25 | An AE is any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. |
| Number of Participants With Abnormal Vital Signs of Potential Clinical Importance: Systolic and Distolic Blood Pressure and Heart Rate. | Screening, Day -28, 1, 15, 29, 50, 57 and 169 (follow-up 3) | Vital signs including systolic and diastolic blood pressure and heart rate taken at certain visits from screening to follow-up. Potential Clinical Importance Ranges were systolic blood pressure (\<85 and \>160millimeter of mercury \[mmHg\]), diastolic blood pressure (\<45 and \>100 mmHg) and heart rate (\<40 and \>110 beats per minute \[BPM\]). Number of participants with abnormal systolic blood pressure, diastolic blood pressure and heart rate values of potential clinical importance were summarized. |
| Number of Participants With Clinically Significant Abnormality in 12-lead Electrocardiogram (ECG) | Upto Week 25 | Single 12-lead ECGs were obtained at certain visits from screening to follow-up. ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and Corrected QT (QTc) intervals. Number of participants with clinically significant abnormality in 12-lead ECG readings were summarized. |
| Change From Baseline in ACQ-7 Over 16 Weeks and 24 Weeks | Week 16 and Week 24 | The ACQ-7 is a 7-item questionnaire that provides a measure of a participant's asthma control. Participant responses were recorded on a 7-point scale ranging from zero (no impairment/ limitation) to 6 (total impairment/ limitation). The values of Week 1 is considered as Baseline. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. Change from Baseline of Week 16 and Week 24 are incorporated here which are Follow up weeks. |
| Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Upto Week 25 | Blood samples were collected on each visit from Week 1 to Week 25 to assess the clinical chemistry parameters. Albumin, Calcium, Glucose, Pottasium, Sodium and Total Carbon Di-oxide were analyzed in clinical chemistry. Number of participants with any abnormal clinical chemistry parameters of potential clinical importance are summarized here. |
| Number of Participants With Abnormal Urinanalysis Parameters of Potential Clinical Importance | Upto Week 25 | Samples were collected on each visit from Week 1 to Week 25 for urinalysis. Number of participants with any abnormal urinalysis parameters of potential clinical importance are summarized here. |
| Pharmacokinetic (PK) Parameter: Area Under the Concentration-time Curve Over the Dosing Interval (AUC (0-τ)). | Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. | Plasma concentration-time data were well described by a 2-compartment model with first order elimination. Plasma concentrations of GSK679586 were determined at Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672 h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. However, the derived PK parameters were determined only for the day of infusion administration. i.e. Day 1, Day 29 and Day 57. The AUC at Day 1 indicates AUC(0-1 h), Day 29 indicated AUC(0-672 h) and Day 57 indicated AUC(0-1344h). AUC(0-τ) for each participant was reconstructed from sparse PK sampling using Bayesian prediction obtained from a population PK model using nonlinear mixed effects methods (NONMEM, version V). |
| PK Parameter:Maximum Observed Concentration (Cmax) | Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672 h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. | Plasma concentration-time data were well described by a 2-compartment model with first order elimination. Plasma concentrations of GSK679586 were determined at Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. However, Cmax were determined only for the day of infusion administration. i.e. Day 1, Day 29 and Day 57. The Cmax at Day 1 indicates Cmax(0-1 h), Day 29 indicated Cmax(0-672 h) and Day 57 indicated Cmax(0-1344 h). Cmax for each participant was reconstructed from sparse PK sampling using Bayesian prediction obtained from a population PK model using nonlinear mixed effects methods (NONMEM, version V). |
| PK Parameter: Systemic Clearance of Parent Drug | Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672 h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. | Plasma concentration-time data were well described by a 2-compartment model with first order elimination. Plasma concentrations of GSK679586 were determined at Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. However, systemic clearance were determined only for the day of infusion administration. i.e. Day 1, Day 29 and Day 57. The systemic clearance at Day 1 indicates systemic clearance(0-1 h), Day 29 indicated systemic clearance(0-672 h) and Day 57 indicated systemic clearance(0-1344 h). Systemic clearance of parent drug for each participant was reconstructed from sparse PK sampling using Bayesian prediction obtained from a population PK model using nonlinear mixed effects methods (NONMEM, version V). |
| PK Parameter: Volume of Distribution | Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672 h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. | Plasma concentration-time data were well described by a 2-compartment model with first order elimination. Plasma concentrations of GSK679586 were determined at Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672 h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. However, volume of distribution were determined only for the day of infusion administration. i.e. Day 1, Day 29 and Day 57. The volume of distribution at Day 1 indicates volume of distribution(0-1 h), Day 29 indicated volume of distribution (0-672 h) and Day 57 indicated volume of distribution (0-1344 h). Volume of distribution for each participant was reconstructed from sparse PK sampling using Bayesian prediction obtained from a population PK model using nonlinear mixed effects methods (NONMEM, version V). The 2-compartment model provided the data for volume of distribution of central compartment (V1) and volume distribution of peripheral compartment (V2). |
| Number of Participants With Confirmed Positive Anti-GSK679586 Antibody Results After Initiation of Study Treatment | Up to Week 25 | Serum samples were tested for presence of anti-GSK679586 antibodies. Blood samples were collected via an indwelling cannula or by direct venepuncture collected into a serum separator tube and allowed to clot for 1 to 2 hours. Samples were centrifuged and the resultant serum was transferred to 3 separate cryovials and stored at -80°C until shipped on dry ice to the central laboratory. Samples were analyzed in a tiered assay format. Number of participants with confirmed positive Anti-GSK679586 antibody results after initiation of study treatment were reported. |
| Number of Participants With Abnormal Hematological Parameters of Potential Clinical Importance | Upto Week 25 | Blood samples were collected on each visit from Week 1 to Week 25 to assess the haematological parameters. White Blood Cells count, Neutrophils, Haemoglobin, Hematocrit, Count and Lymphocytes were analyzed in haematology. Number of participants with any abnormal hematological parameters of potential clinical importance are summarized here. |
Countries
France, Germany, Netherlands, Norway, Poland, South Africa, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted in participants with severe asthmatics from 9-Dec-2008 to 19-July-2010 at 35 study centers in France (7), United States (6), United Kingdom (5), Poland (5), South Africa (4), Germany (3), Netherlands (3) and Norway (2).
Pre-assignment details
During run-in period of 28 days each participant's inhaled corticosteroid (ICS) dose was up-titrated to 1000 microgram (μg)/day fluticasone propionate. Participants already taking ≥ 1000 µg/day fluticasone propionate or equivalent prior to study remained on their pre-study dose. Total of 198 participants were randomized and treated in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a total of three once-monthly IV infusions of sodium chloride placebo in a volume matched to the volume that would had been administered if the participant had been randomized to active treatment in order to maintain the integrity of the study blind. The IV infusions were administered by qualified study personnel, and were administered over 1 hour using a programmable infusion pump. | 99 |
| GSK679586 10 mg/kg Participants received a total of 3 once-monthly IV infusions of 10 mg/kg GSK679586 diluted with sterile, normal saline to a concentration of 25 mg/mL. The final solution volume was 40 to 60 mL, depending on participants weight. The IV infusions were administered by qualified study personnel, and were administered over 1 hour using a programmable infusion pump. | 99 |
| Total | 198 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Placebo | GSK679586 10 mg/kg | Total |
|---|---|---|---|
| Age, Continuous | 51.2 Years STANDARD_DEVIATION 11.78 | 51.2 Years STANDARD_DEVIATION 11.13 | 51.2 Years STANDARD_DEVIATION 11.43 |
| Race/Ethnicity, Customized African American/African Heritage | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Japanese/East Asian/South East Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 95 Participants | 96 Participants | 191 Participants |
| Sex: Female, Male Female | 49 Participants | 51 Participants | 100 Participants |
| Sex: Female, Male Male | 50 Participants | 48 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 99 | 1 / 99 |
| other Total, other adverse events | 19 / 99 | 27 / 99 |
| serious Total, serious adverse events | 5 / 99 | 8 / 99 |
Outcome results
Primary
Change From Baseline in Asthma Control Questionnaire (ACQ-7) Over 12 Weeks
The ACQ-7 consists of 7 questions scored between zero (no impairment/ limitation) to 6 (total impairment/ limitation). The values of Week 1 is considered as Baseline. ACQ-7 was calculated as the average of the 7 scores. If any one individual score was missing, the ACQ-7 was set to missing.The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well.
Time frame: Baseline to Week 12
Population: Intent-to-Treat (ITT) population was comprised of all participants who are randomized and receive at least the first dose of study medication. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Over 12 Weeks | Week 2 | -0.1 Scores on Scale | Standard Error 0.06 |
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Over 12 Weeks | Week 4 | -0.1 Scores on Scale | Standard Error 0.06 |
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Over 12 Weeks | Week 8 | -0.2 Scores on Scale | Standard Error 0.07 |
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Over 12 Weeks | Week 12 | -0.3 Scores on Scale | Standard Error 0.08 |
| GSK679586 10 mg/kg | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Over 12 Weeks | Week 12 | -0.4 Scores on Scale | Standard Error 0.09 |
| GSK679586 10 mg/kg | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Over 12 Weeks | Week 2 | -0.2 Scores on Scale | Standard Error 0.06 |
| GSK679586 10 mg/kg | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Over 12 Weeks | Week 8 | -0.3 Scores on Scale | Standard Error 0.07 |
| GSK679586 10 mg/kg | Change From Baseline in Asthma Control Questionnaire (ACQ-7) Over 12 Weeks | Week 4 | -0.3 Scores on Scale | Standard Error 0.05 |
Comparison: Comparison between GSK679586 10 mg/kg and Placebo at Week 2p-value: 0.195595% CI: [-0.27, 0.06]ANCOVA
Comparison: Comparison between GSK679586 10 mg/kg and Placebo at Week 4p-value: 0.019395% CI: [-0.34, -0.03]Mixed Model Repeated Measures analysis
Comparison: Comparison between GSK679586 10 mg/kg and Placebo at Week 8p-value: 0.615695% CI: [-0.23, 0.14]Mixed Model Repeated Measures analysis
Comparison: Comparison between GSK679586 120 mg/kg and Placebo at Week 12p-value: 0.467295% CI: [-0.31, 0.14]ANCOVA
Secondary
Change From Baseline in ACQ-7 Over 16 Weeks and 24 Weeks
The ACQ-7 is a 7-item questionnaire that provides a measure of a participant's asthma control. Participant responses were recorded on a 7-point scale ranging from zero (no impairment/ limitation) to 6 (total impairment/ limitation). The values of Week 1 is considered as Baseline. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. Change from Baseline of Week 16 and Week 24 are incorporated here which are Follow up weeks.
Time frame: Week 16 and Week 24
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in ACQ-7 Over 16 Weeks and 24 Weeks | Week 16 | -0.3 Scores on Scale | Standard Error 0.08 |
| Placebo | Change From Baseline in ACQ-7 Over 16 Weeks and 24 Weeks | Week 24 | -0.3 Scores on Scale | Standard Error 0.09 |
| GSK679586 10 mg/kg | Change From Baseline in ACQ-7 Over 16 Weeks and 24 Weeks | Week 16 | -0.4 Scores on Scale | Standard Error 0.08 |
| GSK679586 10 mg/kg | Change From Baseline in ACQ-7 Over 16 Weeks and 24 Weeks | Week 24 | -0.2 Scores on Scale | Standard Error 0.08 |
Secondary
Change From Baseline in FEV1 Over 16 Weeks and 24 Weeks
FEV1 is forced expiratory volume in 1 second.Change from Baseline FEV1 was calculated for each of the following visit: Visit 6, Visit 7, Visit 9 and Visit 11. A binary variable was created for each participant with 1 for the responder and 0 for the non nonresponder at each visit. Week 1 was considered as the Baseline. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well. Change from Baseline of Week 16 and Week 24 are incorporated here which are Follow up weeks.
Time frame: Week 16 and 24
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in FEV1 Over 16 Weeks and 24 Weeks | Week 16 | 0.109 mL | Standard Error 0.0345 |
| Placebo | Change From Baseline in FEV1 Over 16 Weeks and 24 Weeks | Week 24 | 0.065 mL | Standard Error 0.0356 |
| GSK679586 10 mg/kg | Change From Baseline in FEV1 Over 16 Weeks and 24 Weeks | Week 16 | 0.010 mL | Standard Error 0.0392 |
| GSK679586 10 mg/kg | Change From Baseline in FEV1 Over 16 Weeks and 24 Weeks | Week 24 | -0.021 mL | Standard Error 0.0368 |
Secondary
Change From Baseline in Forced Expiratory Volume (FEV1) Over 12 Weeks.
FEV1 is forced expiratory volume in 1 second.Change from Baseline FEV1 was calculated for each of the following visit: Visit 6, Visit 7, Visit 9 and Visit 11. A binary variable was created for each participant with 1 for the responder and 0 for the non nonresponder at each visit. Week 1 was considered as the Baseline. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline was set to missing as well.
Time frame: Baseline to Week 12
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) Over 12 Weeks. | Week 2 | 0.009 Millilitre (mL) | Standard Error 0.0275 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) Over 12 Weeks. | Week 4 | 0.033 Millilitre (mL) | Standard Error 0.0331 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) Over 12 Weeks. | Week 8 | 0.035 Millilitre (mL) | Standard Error 0.0335 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) Over 12 Weeks. | Week 12 | 0.078 Millilitre (mL) | Standard Error 0.0331 |
| GSK679586 10 mg/kg | Change From Baseline in Forced Expiratory Volume (FEV1) Over 12 Weeks. | Week 12 | -0.016 Millilitre (mL) | Standard Error 0.0373 |
| GSK679586 10 mg/kg | Change From Baseline in Forced Expiratory Volume (FEV1) Over 12 Weeks. | Week 2 | 0.002 Millilitre (mL) | Standard Error 0.0277 |
| GSK679586 10 mg/kg | Change From Baseline in Forced Expiratory Volume (FEV1) Over 12 Weeks. | Week 8 | -0.009 Millilitre (mL) | Standard Error 0.0313 |
| GSK679586 10 mg/kg | Change From Baseline in Forced Expiratory Volume (FEV1) Over 12 Weeks. | Week 4 | 0.037 Millilitre (mL) | Standard Error 0.0288 |
Comparison: Comparison between GSK679586 10 mg/kg and Placebo at Week 2p-value: 0.769395% CI: [-0.08, 0.06]ANCOVA
Comparison: Comparison between GSK679586 10 mg/kg and Placebo at Week 4p-value: 0.898795% CI: [-0.08, 0.09]Mixed Model Repeated Measures analysis
Comparison: Comparison between GSK679586 10 mg/kg and Placebo at Week 8p-value: 0.423195% CI: [-0.12, 0.05]Mixed Model Repeated Measures analysis
Comparison: Comparison between GSK679586 10 mg/kg and Placebo at Week 12p-value: 0.053795% CI: [-0.19, 0]Mixed Model Repeated Measures analysis
Secondary
Number of Participants Who Demonstrated a Clinically Meaningful Change in ACQ-7 Over the 12 Weeks Assessment Period.
The ACQ-7 is a 7-item questionnaire that provides a measure of a participant's asthma control. Participant responses were recorded on a 7-point scale ranging from zero (no impairment/ limitation) to 6 (total impairment/ limitation). The percentage of participants who were classified as responders for ACQ-7, defined as a clinically meaningful decrease from baseline in ACQ-7 of at least 0.50, was generally similar between treatment groups at each visit and over the 12-week treatment period.
Time frame: Upto 12 weeks
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Who Demonstrated a Clinically Meaningful Change in ACQ-7 Over the 12 Weeks Assessment Period. | Week 2 | 16 Participants |
| Placebo | Number of Participants Who Demonstrated a Clinically Meaningful Change in ACQ-7 Over the 12 Weeks Assessment Period. | Week 4 | 22 Participants |
| Placebo | Number of Participants Who Demonstrated a Clinically Meaningful Change in ACQ-7 Over the 12 Weeks Assessment Period. | Week 8 | 31 Participants |
| Placebo | Number of Participants Who Demonstrated a Clinically Meaningful Change in ACQ-7 Over the 12 Weeks Assessment Period. | Week 12 | 33 Participants |
| GSK679586 10 mg/kg | Number of Participants Who Demonstrated a Clinically Meaningful Change in ACQ-7 Over the 12 Weeks Assessment Period. | Week 12 | 36 Participants |
| GSK679586 10 mg/kg | Number of Participants Who Demonstrated a Clinically Meaningful Change in ACQ-7 Over the 12 Weeks Assessment Period. | Week 2 | 20 Participants |
| GSK679586 10 mg/kg | Number of Participants Who Demonstrated a Clinically Meaningful Change in ACQ-7 Over the 12 Weeks Assessment Period. | Week 8 | 26 Participants |
| GSK679586 10 mg/kg | Number of Participants Who Demonstrated a Clinically Meaningful Change in ACQ-7 Over the 12 Weeks Assessment Period. | Week 4 | 29 Participants |
Secondary
Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance
Blood samples were collected on each visit from Week 1 to Week 25 to assess the clinical chemistry parameters. Albumin, Calcium, Glucose, Pottasium, Sodium and Total Carbon Di-oxide were analyzed in clinical chemistry. Number of participants with any abnormal clinical chemistry parameters of potential clinical importance are summarized here.
Time frame: Upto Week 25
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | High glucose | 10 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased ALT | 2 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased total bilirubin | 2 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased alkaline phosphatase | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Low glucose | 4 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased serum potassium | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased AST | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased serum calcium | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Low total carbondioxide | 14 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased serum calcium | 0 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Low total carbondioxide | 17 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | High glucose | 17 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Low glucose | 3 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased total bilirubin | 2 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased AST | 2 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased ALT | 1 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased alkaline phosphatase | 0 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Clinical Chemistry Parameters of Potential Clinical Importance | Increased serum potassium | 2 Participants |
Secondary
Number of Participants With Abnormal Hematological Parameters of Potential Clinical Importance
Blood samples were collected on each visit from Week 1 to Week 25 to assess the haematological parameters. White Blood Cells count, Neutrophils, Haemoglobin, Hematocrit, Count and Lymphocytes were analyzed in haematology. Number of participants with any abnormal hematological parameters of potential clinical importance are summarized here.
Time frame: Upto Week 25
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Hematological Parameters of Potential Clinical Importance | Low lymphocyte count | 5 Participants |
| Placebo | Number of Participants With Abnormal Hematological Parameters of Potential Clinical Importance | Increased white blood cell count | 3 Participants |
| Placebo | Number of Participants With Abnormal Hematological Parameters of Potential Clinical Importance | Low neutrophils count | 3 Participants |
| Placebo | Number of Participants With Abnormal Hematological Parameters of Potential Clinical Importance | Low platelet count | 1 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Hematological Parameters of Potential Clinical Importance | Low platelet count | 1 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Hematological Parameters of Potential Clinical Importance | Low lymphocyte count | 3 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Hematological Parameters of Potential Clinical Importance | Low neutrophils count | 4 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Hematological Parameters of Potential Clinical Importance | Increased white blood cell count | 1 Participants |
Secondary
Number of Participants With Abnormal Urinanalysis Parameters of Potential Clinical Importance
Samples were collected on each visit from Week 1 to Week 25 for urinalysis. Number of participants with any abnormal urinalysis parameters of potential clinical importance are summarized here.
Time frame: Upto Week 25
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Abnormal Urinanalysis Parameters of Potential Clinical Importance | 0 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Urinanalysis Parameters of Potential Clinical Importance | 0 Participants |
Secondary
Number of Participants With Abnormal Vital Signs of Potential Clinical Importance: Systolic and Distolic Blood Pressure and Heart Rate.
Vital signs including systolic and diastolic blood pressure and heart rate taken at certain visits from screening to follow-up. Potential Clinical Importance Ranges were systolic blood pressure (\<85 and \>160millimeter of mercury \[mmHg\]), diastolic blood pressure (\<45 and \>100 mmHg) and heart rate (\<40 and \>110 beats per minute \[BPM\]). Number of participants with abnormal systolic blood pressure, diastolic blood pressure and heart rate values of potential clinical importance were summarized.
Time frame: Screening, Day -28, 1, 15, 29, 50, 57 and 169 (follow-up 3)
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Vital Signs of Potential Clinical Importance: Systolic and Distolic Blood Pressure and Heart Rate. | Systolic Blood Pressure, High | 6 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs of Potential Clinical Importance: Systolic and Distolic Blood Pressure and Heart Rate. | Diastolic Blood Pressure, High | 8 Participants |
| Placebo | Number of Participants With Abnormal Vital Signs of Potential Clinical Importance: Systolic and Distolic Blood Pressure and Heart Rate. | Heart Rate | 0 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Vital Signs of Potential Clinical Importance: Systolic and Distolic Blood Pressure and Heart Rate. | Systolic Blood Pressure, High | 6 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Vital Signs of Potential Clinical Importance: Systolic and Distolic Blood Pressure and Heart Rate. | Diastolic Blood Pressure, High | 4 Participants |
| GSK679586 10 mg/kg | Number of Participants With Abnormal Vital Signs of Potential Clinical Importance: Systolic and Distolic Blood Pressure and Heart Rate. | Heart Rate | 1 Participants |
Secondary
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect.
Time frame: Up to Week 25
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 49 Participants |
| Placebo | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 5 Participants |
| GSK679586 10 mg/kg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 52 Participants |
| GSK679586 10 mg/kg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 8 Participants |
Secondary
Number of Participants With Clinically Significant Abnormality in 12-lead Electrocardiogram (ECG)
Single 12-lead ECGs were obtained at certain visits from screening to follow-up. ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and Corrected QT (QTc) intervals. Number of participants with clinically significant abnormality in 12-lead ECG readings were summarized.
Time frame: Upto Week 25
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Significant Abnormality in 12-lead Electrocardiogram (ECG) | Day 29, 1.5 hours | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormality in 12-lead Electrocardiogram (ECG) | Day 29, 6 hours | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormality in 12-lead Electrocardiogram (ECG) | Day 50 | 0 Participants |
| GSK679586 10 mg/kg | Number of Participants With Clinically Significant Abnormality in 12-lead Electrocardiogram (ECG) | Day 29, 1.5 hours | 1 Participants |
| GSK679586 10 mg/kg | Number of Participants With Clinically Significant Abnormality in 12-lead Electrocardiogram (ECG) | Day 29, 6 hours | 1 Participants |
| GSK679586 10 mg/kg | Number of Participants With Clinically Significant Abnormality in 12-lead Electrocardiogram (ECG) | Day 50 | 2 Participants |
Secondary
Number of Participants With Confirmed Positive Anti-GSK679586 Antibody Results After Initiation of Study Treatment
Serum samples were tested for presence of anti-GSK679586 antibodies. Blood samples were collected via an indwelling cannula or by direct venepuncture collected into a serum separator tube and allowed to clot for 1 to 2 hours. Samples were centrifuged and the resultant serum was transferred to 3 separate cryovials and stored at -80°C until shipped on dry ice to the central laboratory. Samples were analyzed in a tiered assay format. Number of participants with confirmed positive Anti-GSK679586 antibody results after initiation of study treatment were reported.
Time frame: Up to Week 25
Population: ITT Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Confirmed Positive Anti-GSK679586 Antibody Results After Initiation of Study Treatment | 4 Participants |
| GSK679586 10 mg/kg | Number of Participants With Confirmed Positive Anti-GSK679586 Antibody Results After Initiation of Study Treatment | 2 Participants |
Secondary
Percentage of Participants Who Demonstrated a Clinically Meaningful Increase in FEV1 Over the 12 Week Assessment Period
FEV1 is forced expiratory volume in 1 second.A participant is defined as a FEV1 responder if he/she achieves a change from baseline FEV1 of \>=200ml. To evaluate whether the participant was a responder over 12 weeks, change from baseline FEV1 over 12 weeks was calculated by taking the mean of the changes at Visit 7, Visit 9 and Visit 11. A binary variable was created for each participant with 1 for the responder and 0 for the non-responder. If either Visit 9 or Visit 11 FEV1 data are missing, then the binary variable for the responder over 12 weeks was set to be missing. If Visit 7 data were missing, but Visit 9 and Visit 11 data were available, then the binary variable for the responder over 12 weeks was still calculated.
Time frame: Upto 12 weeks
Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Demonstrated a Clinically Meaningful Increase in FEV1 Over the 12 Week Assessment Period | Week 2 | 16 Percentage of Participants |
| Placebo | Percentage of Participants Who Demonstrated a Clinically Meaningful Increase in FEV1 Over the 12 Week Assessment Period | Week 4 | 22 Percentage of Participants |
| Placebo | Percentage of Participants Who Demonstrated a Clinically Meaningful Increase in FEV1 Over the 12 Week Assessment Period | Week 8 | 25 Percentage of Participants |
| Placebo | Percentage of Participants Who Demonstrated a Clinically Meaningful Increase in FEV1 Over the 12 Week Assessment Period | Week 12 | 34 Percentage of Participants |
| GSK679586 10 mg/kg | Percentage of Participants Who Demonstrated a Clinically Meaningful Increase in FEV1 Over the 12 Week Assessment Period | Week 12 | 20 Percentage of Participants |
| GSK679586 10 mg/kg | Percentage of Participants Who Demonstrated a Clinically Meaningful Increase in FEV1 Over the 12 Week Assessment Period | Week 2 | 20 Percentage of Participants |
| GSK679586 10 mg/kg | Percentage of Participants Who Demonstrated a Clinically Meaningful Increase in FEV1 Over the 12 Week Assessment Period | Week 8 | 15 Percentage of Participants |
| GSK679586 10 mg/kg | Percentage of Participants Who Demonstrated a Clinically Meaningful Increase in FEV1 Over the 12 Week Assessment Period | Week 4 | 23 Percentage of Participants |
Secondary
Pharmacokinetic (PK) Parameter: Area Under the Concentration-time Curve Over the Dosing Interval (AUC (0-τ)).
Plasma concentration-time data were well described by a 2-compartment model with first order elimination. Plasma concentrations of GSK679586 were determined at Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672 h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. However, the derived PK parameters were determined only for the day of infusion administration. i.e. Day 1, Day 29 and Day 57. The AUC at Day 1 indicates AUC(0-1 h), Day 29 indicated AUC(0-672 h) and Day 57 indicated AUC(0-1344h). AUC(0-τ) for each participant was reconstructed from sparse PK sampling using Bayesian prediction obtained from a population PK model using nonlinear mixed effects methods (NONMEM, version V).
Time frame: Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits.
Population: PK Population comprised of participants in the ITT population for whom a pharmacokinetic samples were obtained and analyzed. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetic (PK) Parameter: Area Under the Concentration-time Curve Over the Dosing Interval (AUC (0-τ)). | Day 1 | 64787259 nanogram*hour/mL | Geometric Coefficient of Variation 16.16 |
| Placebo | Pharmacokinetic (PK) Parameter: Area Under the Concentration-time Curve Over the Dosing Interval (AUC (0-τ)). | Day 29 | 86256087 nanogram*hour/mL | Geometric Coefficient of Variation 18.21 |
| Placebo | Pharmacokinetic (PK) Parameter: Area Under the Concentration-time Curve Over the Dosing Interval (AUC (0-τ)). | Day 57 | 93710588 nanogram*hour/mL | Geometric Coefficient of Variation 22.83 |
Secondary
PK Parameter:Maximum Observed Concentration (Cmax)
Plasma concentration-time data were well described by a 2-compartment model with first order elimination. Plasma concentrations of GSK679586 were determined at Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. However, Cmax were determined only for the day of infusion administration. i.e. Day 1, Day 29 and Day 57. The Cmax at Day 1 indicates Cmax(0-1 h), Day 29 indicated Cmax(0-672 h) and Day 57 indicated Cmax(0-1344 h). Cmax for each participant was reconstructed from sparse PK sampling using Bayesian prediction obtained from a population PK model using nonlinear mixed effects methods (NONMEM, version V).
Time frame: Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672 h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits.
Population: PK Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK Parameter:Maximum Observed Concentration (Cmax) | Day 1 | 278610.6 nanogram (ng)/mL | Geometric Coefficient of Variation 33.4 |
| Placebo | PK Parameter:Maximum Observed Concentration (Cmax) | Day 29 | 332528.4 nanogram (ng)/mL | Geometric Coefficient of Variation 30.85 |
| Placebo | PK Parameter:Maximum Observed Concentration (Cmax) | Day 57 | 355177.0 nanogram (ng)/mL | Geometric Coefficient of Variation 30.31 |
Secondary
PK Parameter: Systemic Clearance of Parent Drug
Plasma concentration-time data were well described by a 2-compartment model with first order elimination. Plasma concentrations of GSK679586 were determined at Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. However, systemic clearance were determined only for the day of infusion administration. i.e. Day 1, Day 29 and Day 57. The systemic clearance at Day 1 indicates systemic clearance(0-1 h), Day 29 indicated systemic clearance(0-672 h) and Day 57 indicated systemic clearance(0-1344 h). Systemic clearance of parent drug for each participant was reconstructed from sparse PK sampling using Bayesian prediction obtained from a population PK model using nonlinear mixed effects methods (NONMEM, version V).
Time frame: Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672 h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits.
Population: PK Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK Parameter: Systemic Clearance of Parent Drug | Day 57 | 0.00010 L/h/kg | Geometric Coefficient of Variation 22.48 |
| Placebo | PK Parameter: Systemic Clearance of Parent Drug | Day 1 | 0.00010 L/h/kg | Geometric Coefficient of Variation 22.76 |
| Placebo | PK Parameter: Systemic Clearance of Parent Drug | Day 29 | 0.00010 L/h/kg | Geometric Coefficient of Variation 22.28 |
Secondary
PK Parameter: Volume of Distribution
Plasma concentration-time data were well described by a 2-compartment model with first order elimination. Plasma concentrations of GSK679586 were determined at Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672 h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits. However, volume of distribution were determined only for the day of infusion administration. i.e. Day 1, Day 29 and Day 57. The volume of distribution at Day 1 indicates volume of distribution(0-1 h), Day 29 indicated volume of distribution (0-672 h) and Day 57 indicated volume of distribution (0-1344 h). Volume of distribution for each participant was reconstructed from sparse PK sampling using Bayesian prediction obtained from a population PK model using nonlinear mixed effects methods (NONMEM, version V). The 2-compartment model provided the data for volume of distribution of central compartment (V1) and volume distribution of peripheral compartment (V2).
Time frame: Day 1 (Pre-dose, 0.25h, 1.00h), Day 4 (72h), Day 29 (672 h), Day 57 (1344h), Day 61 (1440h), Day 85 (2016h), Day 141 (3360h), Day 169 (4032h) and Follow up visits.
Population: PK Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK Parameter: Volume of Distribution | V1, Day 57 | 0.0354 L/Kg | Geometric Coefficient of Variation 34.77 |
| Placebo | PK Parameter: Volume of Distribution | V1, Day 1 | 0.0356 L/Kg | Geometric Coefficient of Variation 33.73 |
| Placebo | PK Parameter: Volume of Distribution | V1, Day 29 | 0.0355 L/Kg | Geometric Coefficient of Variation 34.43 |
| Placebo | PK Parameter: Volume of Distribution | V2, Day 1 | 0.0296 L/Kg | Geometric Coefficient of Variation 0 |
| Placebo | PK Parameter: Volume of Distribution | V2, Day 29 | 0.0296 L/Kg | Geometric Coefficient of Variation 0 |
| Placebo | PK Parameter: Volume of Distribution | V2, Day 57 | 0.0296 L/Kg | Geometric Coefficient of Variation 0 |