Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, chronic obstructive pulmonary disease; Safety, Pharmacokinetics
Brief summary
The primary objective of the study is to assess the safety and tolerability of multiple infusions of andecaliximab (formerly GS-5745) in participants with chronic obstructive pulmonary disease (COPD) as assessed by adverse events (AEs) and laboratory abnormalities.
Interventions
DRUGAndecaliximab
400 mg andecaliximab administered intravenously
Placebo to match andecaliximab administered intravenously
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Weight: ≥ 45 kg to \< 120 kg at screening * Males or non-pregnant, non-lactating females * Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception. Male individuals must refrain from sperm donation for 90 days post last infusion of the study drug * Diagnosis of COPD per Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for at least 6 months prior to screening and anticipated to remain on stable therapy for the duration of the study * Post-bronchodilator forced expiratory volume in one second (FEV1) ≥ 40% predicted * No changes in COPD medications within 30 days prior to randomization * Hepatic panel \[aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin, alkaline phosphatase, lactate dehydrogenase (LDH)\] ≤ 2 times the upper limit of the normal range (ULN) * Serum creatinine ≤ 2.0 * Hemoglobin ≥ 8.5 g/dL (both males and females) * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (1,500 mm\^3) * Platelets ≥ 100 x 10\^9/L Key
Exclusion criteria
* Clinically significant active infection as judged by the investigator during screening * Known history of HIV, hepatitis B or C during screening. Individuals who are hepatitis B surface antigen positive, but who received a successful series of hepatitis B vaccinations and never had the disease remain eligible * A positive QuantiFERON-TB GOLD test during screening * History of malignancy within the last 5 years except for patients who have been treated locally for non-melanoma skin cancer or cervical carcinoma in situ * Any serious cardiac event such as myocardial infarction, unstable or life-threatening arrhythmia, hospitalization for cardiac failure within 6 months prior to randomization or any significant or new electrocardiogram (ECG) finding at Visit 1 as judged by the Investigator * A hospitalization for a respiratory event such as, but not limited to, COPD, pneumonia, bronchiolitis, within the previous 6 months prior to randomization * Chronic lung disease other than COPD such as: asthma, cystic fibrosis or fibrotic disease, α-1-antitrypsin deficiency, interstitial lung disease, pulmonary thromboembolic disease, or bronchiectasis * Chronic use of systemic corticosteroids and/or treatment with systemic corticosteroids for an acute exacerbation of COPD (AECOPD) event, or other medical condition not requiring hospitalization, within 90 days of randomization. * Treatment with antibiotics for an AECOPD event, or other medical condition not requiring hospitalization within 90 days of randomization, or any minor medical event not requiring hospitalization within 14 days of randomization. * Treatment with any marketed or investigational biologic within 5 half-lives of the molecule or if unknown within 90 days of screening * Individuals currently on nonbiologic immune modulator medications such as: azathioprine, cyclosporine, hydroxychloroquine, leflunomide, methotrexate, mycophenolate mofetil, sulfasalazine, tofacitinib, within 90 days of randomization Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events | First dose date up to Day 29 plus 30 days | — |
| Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | First dose date up to Day 29 plus 30 days | A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline and occurring after the first dose of study drug and within 30 days after last study drug administration. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The most severe graded abnormality from all tests was counted for each participant. |
| Percentage of Participants Who Developed Anti-andecaliximab Antibodies | Day 43 | The presence of anti-andecaliximab antibodies in serum samples was determined using an electrochemiluminescent (ECL) assay that detects antibodies that bind to andecaliximab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter of Andecaliximab: Cmax for Days 1, 15 and 29 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes | Cmax is defined as the maximum observed plasma concentration of drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43. |
| PK Parameter of Andecaliximab: Tmax for Days 1, 15 and 29 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes | Tmax is defined as the time (observed time point) of Cmax. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43. |
| PK Parameter of Andecaliximab: Clast for Days 1, 15 and 29 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes | Clast is defined as the last observable concentration of drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43. |
| PK Parameter of Andecaliximab: Tlast for Days 1, 15 and 29 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes | Tlast is defined as the time (observed time point) of Clast. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43. |
| Pharmacokinetic (PK) Parameter of Andecaliximab: AUClast for Days 1, 15 and 29 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes | AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43. |
| PK Parameter of Andecaliximab: CL for Day 1 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes | Clearance (CL) is defined as the systemic clearance of the drug following intravenous administration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. |
| PK Parameter of Andecaliximab: Vz for Day 1 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes | Vz is defined as the volume of distribution of the drug after intravenous administration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. |
| PK Parameter of Andecaliximab: Vss for Day 1 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes | Vss is defined as the volume of distribution of the drug at steady state after intravenous administration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. |
| PK Parameter of Andecaliximab: t1/2 for Day 1 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes | t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. |
| PK Parameter of Andecaliximab: λz for Day 1 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes | λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. |
| PK Parameter of Andecaliximab: AUCinf for Day 1 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes | AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. |
| PK Parameter of Andecaliximab: %AUCexp for Day 1 | Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes | %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in United States. The first participant was screened on 11 March 2014. The last study visit occurred on 27 October 2014.
Pre-assignment details
33 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Andecaliximab Participants received IV infusion of andecaliximab 400 mg once every 2 weeks for a total of 3 infusions. | 8 |
| Placebo Participants received IV infusion of placebo once every 2 weeks for a total of 3 infusions. | 3 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrew Consent | 0 | 1 |
Baseline characteristics
| Characteristic | Andecaliximab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 3.3 | 56 years STANDARD_DEVIATION 3.5 | 62 years STANDARD_DEVIATION 5 |
| Race/Ethnicity, Customized Black | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 7 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 3 |
| other Total, other adverse events | 6 / 8 | 1 / 3 |
| serious Total, serious adverse events | 0 / 8 | 0 / 3 |
Outcome results
Primary
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time frame: First dose date up to Day 29 plus 30 days
Population: The Safety Analysis Set included participants who were randomized and received at least 1 infusion of study drug (andecaliximab or placebo).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Andecaliximab | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 75.0 percentage of participants |
| Placebo | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 33.3 percentage of participants |
Primary
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline and occurring after the first dose of study drug and within 30 days after last study drug administration. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The most severe graded abnormality from all tests was counted for each participant.
Time frame: First dose date up to Day 29 plus 30 days
Population: Participants in the Safety Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Andecaliximab | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 1 | 75.0 percentage of participants |
| Andecaliximab | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 3 | 0.0 percentage of participants |
| Andecaliximab | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 2 | 12.5 percentage of participants |
| Andecaliximab | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 4 | 0.0 percentage of participants |
| Andecaliximab | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Any Post-Baseline Toxicity Grade | 87.5 percentage of participants |
| Placebo | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 4 | 0.0 percentage of participants |
| Placebo | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Any Post-Baseline Toxicity Grade | 100.0 percentage of participants |
| Placebo | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 1 | 100.0 percentage of participants |
| Placebo | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 2 | 0.0 percentage of participants |
| Placebo | Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities | Grade 3 | 0.0 percentage of participants |
Primary
Percentage of Participants Who Developed Anti-andecaliximab Antibodies
The presence of anti-andecaliximab antibodies in serum samples was determined using an electrochemiluminescent (ECL) assay that detects antibodies that bind to andecaliximab.
Time frame: Day 43
Population: The immunogenicity analysis set included participants who received any amount of andecaliximab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Andecaliximab | Percentage of Participants Who Developed Anti-andecaliximab Antibodies | Day 43 Positive Anti-Drug Antibody (ADA) Response | 12.5 percentage of participants |
| Andecaliximab | Percentage of Participants Who Developed Anti-andecaliximab Antibodies | Day 43 Negative ADA Response | 75.0 percentage of participants |
| Andecaliximab | Percentage of Participants Who Developed Anti-andecaliximab Antibodies | Unknown (no ADA sample available) | 12.5 percentage of participants |
Secondary
Pharmacokinetic (PK) Parameter of Andecaliximab: AUClast for Days 1, 15 and 29
AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes
Population: The PK analysis set included all participants in the safety analysis set who have an evaluable PK profile.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Andecaliximab | Pharmacokinetic (PK) Parameter of Andecaliximab: AUClast for Days 1, 15 and 29 | Day 1 | 1206.7 day*ug/mL | Standard Deviation 357.75 |
| Andecaliximab | Pharmacokinetic (PK) Parameter of Andecaliximab: AUClast for Days 1, 15 and 29 | Day 15 | 1880.5 day*ug/mL | Standard Deviation 600.33 |
| Andecaliximab | Pharmacokinetic (PK) Parameter of Andecaliximab: AUClast for Days 1, 15 and 29 | Day 29 | 1822.2 day*ug/mL | Standard Deviation 283.39 |
Secondary
PK Parameter of Andecaliximab: %AUCexp for Day 1
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: %AUCexp for Day 1 | 19.97 percentage of AUC | Standard Deviation 12.781 |
Secondary
PK Parameter of Andecaliximab: AUCinf for Day 1
AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: AUCinf for Day 1 | 1398.1 day*ug/mL | Standard Deviation 265.26 |
Secondary
PK Parameter of Andecaliximab: Clast for Days 1, 15 and 29
Clast is defined as the last observable concentration of drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: Clast for Days 1, 15 and 29 | Day 1 | 37.07 ug/mL | Standard Deviation 18.74 |
| Andecaliximab | PK Parameter of Andecaliximab: Clast for Days 1, 15 and 29 | Day 15 | 50.27 ug/mL | Standard Deviation 14.724 |
| Andecaliximab | PK Parameter of Andecaliximab: Clast for Days 1, 15 and 29 | Day 29 | 71.74 ug/mL | Standard Deviation 23.905 |
Secondary
PK Parameter of Andecaliximab: CL for Day 1
Clearance (CL) is defined as the systemic clearance of the drug following intravenous administration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: CL for Day 1 | 296.5 mL/day | Standard Deviation 64.67 |
Secondary
PK Parameter of Andecaliximab: Cmax for Days 1, 15 and 29
Cmax is defined as the maximum observed plasma concentration of drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: Cmax for Days 1, 15 and 29 | Day 1 | 236.7 ug/mL | Standard Deviation 62.7 |
| Andecaliximab | PK Parameter of Andecaliximab: Cmax for Days 1, 15 and 29 | Day 15 | 255.9 ug/mL | Standard Deviation 71.25 |
| Andecaliximab | PK Parameter of Andecaliximab: Cmax for Days 1, 15 and 29 | Day 29 | 270.6 ug/mL | Standard Deviation 46.48 |
Secondary
PK Parameter of Andecaliximab: t1/2 for Day 1
t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: t1/2 for Day 1 | 5.24 day | Standard Deviation 1.102 |
Secondary
PK Parameter of Andecaliximab: Tlast for Days 1, 15 and 29
Tlast is defined as the time (observed time point) of Clast. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: Tlast for Days 1, 15 and 29 | Day 1 | 12.96 day | Standard Deviation 2.582 |
| Andecaliximab | PK Parameter of Andecaliximab: Tlast for Days 1, 15 and 29 | Day 15 | 14.79 day | Standard Deviation 1.737 |
| Andecaliximab | PK Parameter of Andecaliximab: Tlast for Days 1, 15 and 29 | Day 29 | 13.45 day | Standard Deviation 1.379 |
Secondary
PK Parameter of Andecaliximab: Tmax for Days 1, 15 and 29
Tmax is defined as the time (observed time point) of Cmax. Data for Day 1 was generated based on the data collected from Day 1 through Day 15. Data for Day 15 was generated based on the data collected from Day 15 through Day 29. Data for Day 29 was generated based on the data collected from Day 29 through Day 43.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day3, Day 8, Day 15 (pre-infusion; and 30 minutes post end of infusion), Day 29 (pre-infusion; and 30 minutes post end of infusion), Day 36 and Day 43; Infusion duration = 30 to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: Tmax for Days 1, 15 and 29 | Day 1 | 0.08 day | Standard Deviation 0.076 |
| Andecaliximab | PK Parameter of Andecaliximab: Tmax for Days 1, 15 and 29 | Day 15 | 0.02 day | Standard Deviation 0 |
| Andecaliximab | PK Parameter of Andecaliximab: Tmax for Days 1, 15 and 29 | Day 29 | 0.02 day | Standard Deviation 0.001 |
Secondary
PK Parameter of Andecaliximab: Vss for Day 1
Vss is defined as the volume of distribution of the drug at steady state after intravenous administration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: Vss for Day 1 | 2178.7 mL | Standard Deviation 450.66 |
Secondary
PK Parameter of Andecaliximab: Vz for Day 1
Vz is defined as the volume of distribution of the drug after intravenous administration. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: Vz for Day 1 | 2200.9 mL | Standard Deviation 442.03 |
Secondary
PK Parameter of Andecaliximab: λz for Day 1
λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. Data for Day 1 was generated based on the data collected from Day 1 through Day 15.
Time frame: Day 1 (pre-infusion; 30 minutes and 4 hours post end of infusion), Day 3, Day 8, and Day 15 (pre-infusion); Infusion duration = 30 minutes to 35 minutes
Population: Participants in the PK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Andecaliximab | PK Parameter of Andecaliximab: λz for Day 1 | 0.137 1/day | Standard Deviation 0.0263 |