Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
Assess the safety of CHF10067 (study drug) and any side effects that might be associated with it. The study also evaluated how much of the study drug gets into the bloodstream and how long the body takes to remove it. The body's immune response to the study drug was evaluated. Chiesi conducted this study in patients affected by idiopathic pulmonary fibrosis (IPF, a progressive and chronic lung disease). Chiesi performed this study to establish the drug doses that would be suitable for future studies (a dose finding study).
Detailed description
The principal aim of this study was to obtain safety and tolerability data when CHF10067 was administered intravenously as single ascending doses to subjects with IPF (a progressive and chronic lung disease). This information, together with the pharmacokinetic (PK) and immunogenicity data is part of a dose finding efforts, for future clinical studies. The effect of CHF10067 on transglutaminase 2 (TG2) levels was also investigated as an exploratory endpoint. A sequential group, single ascending dose design has been chosen for safety reasons because CHF10067 is in the early stages of clinical development and no data in the IPF population has been collected so far. In addition, sentinel dosing was used so that in each cohort 2 subjects (1 CHF10067 and 1 placebo) was administered at least 24 hours, before the remaining 6 subjects. The study was double-blind and placebo-controlled to avoid bias in the collection and evaluation of data during its conduct. Placebo was chosen as the comparison treatment to assess whether any observed effects are treatment-related or reflect the study conditions.
Interventions
BIOLOGICALCHF10067 starting dose -- 1000mg (Cohort A)
Intravenous administration of a starting dose of the monoclonal antibody
BIOLOGICALCHF10067 intermediate dose -- 2000mg (Cohort B)
Intravenous administration of an intermediate dose of the monoclonal antibody
BIOLOGICALCHF10067 high dose -- 3000mg (Cohort C)
Intravenous administration of a high dose of the monoclonal antibody
DRUGPlacebo
Intravenous administration of a physiological solution as placebo
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The Investigational Medicinal Product (IMP) was blinded for the participant, investigators, and the sponsor. At the study site an unblinded pharmacist (or designee) prepared the IMP and an unblinded clinical research associate checked the documents of the IMP preparation.
Intervention model description
Treatment with single dose escalation: 3 separate cohorts received 3 incremental doses of Investigational Medicinal Product (IMP). Each cohort started when the previous cohort was completed and the data were evaluated by the Safety Advisory Committee.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject's written informed consent obtained prior to any study-related procedure. * Males or females, of any race, aged ≥ 40 years of age. * Body weight ≥ 45 kg. * Diagnosis of IPF as defined by current American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines. Diagnosis of IPF must be within the past 5 years prior to enrolment, and in the opinion of the Investigator, has been stable for at least 3 months. * Subjects not receiving any IPF treatment (including subjects with previous use of antifibrotic treatment that has been stopped for at least 2 weeks prior to screening) or receiving well-tolerated standard of care approved treatments at a stable dose for at least 8 weeks prior to screening (nintedanib or pirfenidone) and it is anticipated the dose will remain unchanged throughout the study. * Forced vital capacity (FVC) ≥ 50% of predicted and ratio of forced expiratory volume in the first second (FEV1)/FVC ≥ 0.7 at screening. * Diffusing capacity of the lung for carbon monoxide (DLCO; corrected for haemoglobin) ≥ 35% at screening. * Able to understand the study procedures and the risks involved. * Male and Female subjects following contraceptive requirements detailed in the study protocol.
Exclusion criteria
* History of lower respiratory tract infection within 4 weeks prior to screening and up to Day 1 of the study. * History of acute exacerbation of IPF within 3 months prior to screening and up to Day 1 of the study * Active diagnosis of lung cancer or a history of lung cancer. * Active cancer or a history of cancer (other than lung cancer) with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). * Infiltrative lung disease other than IPF * Subjects exhibiting unhealed wounds or foot ulcers or have known history of wound healing complications. * Chronic heart failure categorized as New York Heart Association Class II, III, or IV; clinical diagnosis of cor pulmonale requiring specific treatment; or severe pulmonary hypertension * Currently receiving, or have received, a systemic corticosteroid, immunosuppressant, cytotoxic therapy, vasodilator therapy for pulmonary hypertension, or unapproved or investigational treatment for IPF within 4 weeks prior to screening or prior to randomization. * Coronavirus disease-2019 (COVID-19) vaccine at least 7 days before dosing. Any systemic symptoms (e.g. myalgia, fever, chills, fatigue, etc.) after COVID-19 vaccine should subside at least 2 days before the Day 1 visit. * Documented COVID-19 diagnosis within the last 4 weeks or which has not resolved within 7 days prior to screening or before treatment. * Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation or any other substance used in the study. * History of allergic or anaphylactic reaction to human, humanised, chimeric, immunoglobulins (Igs), or murine monoclonal antibodies. * Clinically relevant abnormal laboratory values (clinical chemistry and haematology) at screening suggesting an unknown disease and requiring further clinical investigation or which may impact the safety of the subject or the evaluation of the study results according to Investigator judgement. . * Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | From pre-dose (baseline) up to day 84. | Evaluate reported adverse events (AEs) and serious adverse events (SAEs). The number of subjects affected by AEs or SAEs is presented below. Please note: comprehensive summaries of AEs and SAEs are presented in section 'Adverse Events'; these include the preferred term of the AE or SAE, the number of subjects affected, and the number of events for a each preferred term. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3_Area Under the Concentration-time Curve (AUC) From Zero to Infinity (AUC0-∞) | Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose. | Evaluate the area under the concentration-time curve (AUC) from zero to infinity (AUC0-∞) of CHF10067 after a single dose. |
| 4_Pharmacokinetics -- Maximum Plasma Concentration (Cmax) | Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose. | Evaluate the Cmax (maximum observed concentration) after a single dose of CHF10067. |
| 5_Pharmacokinetics -- Time to Maximum Observed Concentration (Tmax) | Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose. | Evaluate the time to maximum observed concentration (tmax). |
| 6_Pharmacokinetics -- Serum Concentration at the End of Infusion (Cinf) | Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion (up to 6 hours from the start of infusion). | Evaluate serum concentration at the end of infusion (Cinf) of CHF10067. |
| 7_Pharmacokinetics -- Time at the End of Infusion (Tinf) | Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion (up to 6 hours from the start of infusion). | Evaluate the time of serum concentration at the end of infusion (Tinf). Time at the end of the infusion. |
| 8_Pharmacokinetics -- Clearance (CL) | Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose. | Evaluate clearance (CL) of CHF10067. |
| 2_Systemic Exposure [Area Under the Concentration-time Curve From Zero to Time (AUC0-t)] | Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose. | Evaluate the area under the concentration-time curve (AUC) from zero to the last quantifiable concentration (AUC0-t) of CHF10067 after a single dose. |
| 10_Pharmacokinetics -- Terminal Half-life (t1/2) | From pre-dose (baseline) up to day 84. | Evaluate the terminal half-life (t1/2) of CHF10067. |
| 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Pre-dose (baseline), and on 7, 28, 56, and 84 day post-dose. | Forced expiratory volume in the first second (FEV1) parameters, summarised using descriptive statistics at each analysis time point by treatment. Summary results show the change from baseline of the percent predicted. |
| 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Text adjusted Pre-dose (baseline), and on 7, 28, 56, and 84 day post-dose. | Forced vital capacity (FVC) parameters will be summarised using descriptive statistics at each analysis time point by treatment. Summary results show the change from baseline of the percent predicted. |
| 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | From pre-dose (baseline) up to day 84. | Evaluate abnormal changes in systolic and diastolic blood pressure from baseline at any post-baseline time point. |
| 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | Pre-dose (baseline), at day 14, 28, 56, 84, and in case of early termination. | Evaluate the immunogenicity profile of CHF 10067 in serum, with respect to the development of anti-drug antibody (ADA) and neutralising antibody (nAb). A robust immunogenicity profile indicates the potential for the drug to trigger an immune response in patients, leading to the formation of ADAs. These antibodies can affect the drug's efficacy, safety, and pharmacokinetics. Detecting the presence of ADAs in serum samples was performed using an enzyme linked immunosorbent assay (ELISA), a validated assay method. Neutralizing Antibody (nAb) are a subset of ADAs that can interfere with the drug's therapeutic activity by blocking its binding to the target or inhibiting its downstream effects. The presence of ADAs and nAbs can affect the drug's pharmacokinetics (PK) by altering its absorption, distribution, metabolism, and excretion. This can lead to changes in drug exposure and potentially impact efficacy and safety. |
| 9_Pharmacokinetics -- Volume of Distribution (Vz) | Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose. | Evaluate volume of distribution (Vz) CHF10067. |
Countries
North Macedonia, Ukraine, United Kingdom
Participant flow
Recruitment details
For the study, 52 male and female subjects were screened 3-28 days before randomization; of these, 27 subjects were screening failures. Overall, 25 subjects were randomized; of these 1 subject (CHF 10067 3000 mg) did not receive the study medication due to technical reasons.
Participants by arm
| Arm | Count |
|---|---|
| CHF 10067 1000 mg (Test Treatment) A single intravenous (IV) dose of CHF10067
CHF10067 starting dose: Intravenous administration of a starting dose of the monoclonal antibody | 6 |
| CHF 10067 2000 mg (Test Treatment) A single intravenous (IV) dose of CHF10067
CHF10067 intermediate dose: Intravenous administration of an intermediate dose of the monoclonal antibody | 6 |
| CHF 10067 3000 mg (Test Treatment) A single intravenous (IV) dose of CHF10067
CHF10067 high dose: Intravenous administration of an high dose of the monoclonal antibody | 6 |
| Placebo A single dose of placebo (commercial source of 0.9% sodium chloride aqueous solution)
Placebo: Intravenous administration of a physiological solution as placebo | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Not treated due to technical reasons | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | CHF 10067 3000 mg (Test Treatment) | CHF 10067 2000 mg (Test Treatment) | CHF 10067 1000 mg (Test Treatment) |
|---|---|---|---|---|---|
| Age, Continuous | 63.0 years STANDARD_DEVIATION 8.1 | 70.7 years STANDARD_DEVIATION 4.1 | 58.7 years STANDARD_DEVIATION 8.2 | 61.8 years STANDARD_DEVIATION 8 | 60.7 years STANDARD_DEVIATION 7.3 |
| Antifibrotic treatment for IPF Nintedanib | 9 Participants | 3 Participants | 1 Participants | 2 Participants | 3 Participants |
| Antifibrotic treatment for IPF NO | 12 Participants | 2 Participants | 4 Participants | 4 Participants | 2 Participants |
| Antifibrotic treatment for IPF Pirfenidone | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants |
| Antifibrotic treatment for IPF YES | 12 Participants | 4 Participants | 2 Participants | 2 Participants | 4 Participants |
| Body Mass Index (BMI) | 28.51 kg/m^2 STANDARD_DEVIATION 3.42 | 27.80 kg/m^2 STANDARD_DEVIATION 1.9 | 30.02 kg/m^2 STANDARD_DEVIATION 4.18 | 30.23 kg/m^2 STANDARD_DEVIATION 3.66 | 25.98 kg/m^2 STANDARD_DEVIATION 2.17 |
| Duration of smoking | 29.6 years STANDARD_DEVIATION 13.5 | 24.5 years STANDARD_DEVIATION 16.3 | 21.7 years STANDARD_DEVIATION 5.7 | 33.7 years STANDARD_DEVIATION 16.3 | 40.3 years STANDARD_DEVIATION 7.8 |
| FEV1 actual value | 2.313 liters STANDARD_DEVIATION 0.53 | 2.405 liters STANDARD_DEVIATION 0.308 | 2.107 liters STANDARD_DEVIATION 0.628 | 2.550 liters STANDARD_DEVIATION 0.735 | 2.190 liters STANDARD_DEVIATION 0.343 |
| FEV1 % of predicted | 78.59 % of predicted normal value STANDARD_DEVIATION 13.55 | 81.05 % of predicted normal value STANDARD_DEVIATION 10.74 | 77.67 % of predicted normal value STANDARD_DEVIATION 13.64 | 85.75 % of predicted normal value STANDARD_DEVIATION 15.97 | 69.90 % of predicted normal value STANDARD_DEVIATION 11.28 |
| FVC actual value | 2.920 liters STANDARD_DEVIATION 0.762 | 2.965 liters STANDARD_DEVIATION 0.429 | 2.632 liters STANDARD_DEVIATION 0.914 | 3.267 liters STANDARD_DEVIATION 1.116 | 2.818 liters STANDARD_DEVIATION 0.385 |
| FVC % of predicted normal value | 76.74 % of predicted normal value STANDARD_DEVIATION 14.95 | 75.72 % of predicted normal value STANDARD_DEVIATION 10.57 | 75.67 % of predicted normal value STANDARD_DEVIATION 14.11 | 85.23 % of predicted normal value STANDARD_DEVIATION 20.15 | 70.33 % of predicted normal value STANDARD_DEVIATION 13.17 |
| Number of pack-years | 19.62 pack-years STANDARD_DEVIATION 11.43 | 18.00 pack-years STANDARD_DEVIATION 13.98 | 20.00 pack-years STANDARD_DEVIATION 7 | 22.43 pack-years STANDARD_DEVIATION 18.6 | 18.60 pack-years STANDARD_DEVIATION 8.79 |
| Number of subjects with no exacerbations in the 3 months before screening | 24 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 8 Participants | 0 Participants | 5 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 16 Participants | 6 Participants | 1 Participants | 4 Participants | 5 Participants |
| Smoking status at screening E-cigarettes: Ex-smoker | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Smoking status at screening E-cigarettes: Non-smoker | 24 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Smoking status at screening Tobacco: Ex-smoker | 13 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants |
| Smoking status at screening Tobacco: Non-smoker | 11 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants |
| Time since diagnosis | 1.00 years | 1.40 years | 1.21 years | 0.79 years | 1.25 years |
| Type of diagnosis Possible UIP pattern on available HRCT scan prior to screening | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Type of diagnosis Probable UIP pattern HRCT scan prior to screening. Lung biopsy in accordance with HRCT: NA | 9 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants |
| Type of diagnosis Probable UIP pattern HRCT scan prior to screening. Lung biopsy in accordance with HRCT: YES | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Type of diagnosis Probable UIP pattern on available HRCT scan prior to screening. IPF confirmation: YES | 9 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants |
| Type of diagnosis UIP pattern on available HRCT scan prior to screening | 15 Participants | 3 Participants | 4 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 6 | 3 / 6 | 5 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 |
Outcome results
Primary
1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs
Evaluate reported adverse events (AEs) and serious adverse events (SAEs). The number of subjects affected by AEs or SAEs is presented below. Please note: comprehensive summaries of AEs and SAEs are presented in section 'Adverse Events'; these include the preferred term of the AE or SAE, the number of subjects affected, and the number of events for a each preferred term.
Time frame: From pre-dose (baseline) up to day 84.
Population: Safety set: all randomised subjects who received a dose of study treatment, including partial dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | Serious TEAE | 0 Participants |
| CHF 10067 1000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | Non-serious TEAE | 4 Participants |
| CHF 10067 1000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | AE leading to study treatment discontinuation | 0 Participants |
| CHF 10067 1000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | AE leading to death | 0 Participants |
| CHF 10067 2000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | Non-serious TEAE | 3 Participants |
| CHF 10067 2000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | AE leading to study treatment discontinuation | 0 Participants |
| CHF 10067 2000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | AE leading to death | 0 Participants |
| CHF 10067 2000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | Serious TEAE | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | AE leading to study treatment discontinuation | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | Non-serious TEAE | 5 Participants |
| CHF 10067 3000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | AE leading to death | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | Serious TEAE | 1 Participants |
| Placebo | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | AE leading to death | 0 Participants |
| Placebo | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | Non-serious TEAE | 4 Participants |
| Placebo | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | Serious TEAE | 0 Participants |
| Placebo | 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs | AE leading to study treatment discontinuation | 0 Participants |
Secondary
10_Pharmacokinetics -- Terminal Half-life (t1/2)
Evaluate the terminal half-life (t1/2) of CHF10067.
Time frame: From pre-dose (baseline) up to day 84.
Population: Pharmacokinetic set (PK set): all subjects from the safety set, excluding subjects without any valid PK measurement or with important protocol deviations significantly affecting PK, for example, use of non-permitted medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 10_Pharmacokinetics -- Terminal Half-life (t1/2) | 11.7 days | Standard Deviation 2.2 |
| CHF 10067 2000 mg (Test Treatment) | 10_Pharmacokinetics -- Terminal Half-life (t1/2) | 16.8 days | Standard Deviation 2.32 |
| CHF 10067 3000 mg (Test Treatment) | 10_Pharmacokinetics -- Terminal Half-life (t1/2) | 19.1 days | Standard Deviation 1.93 |
Secondary
11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline
Forced expiratory volume in the first second (FEV1) parameters, summarised using descriptive statistics at each analysis time point by treatment. Summary results show the change from baseline of the percent predicted.
Time frame: Pre-dose (baseline), and on 7, 28, 56, and 84 day post-dose.
Population: Safety set: all subjects who were randomised and received a dose of study treatment, including partial dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 84 | 0.13 percent predicted FEV1 | Standard Deviation 5.57 |
| CHF 10067 1000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 56 | 3.18 percent predicted FEV1 | Standard Deviation 3.58 |
| CHF 10067 1000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 28 | 3.76 percent predicted FEV1 | Standard Deviation 3.66 |
| CHF 10067 1000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 7 | 3.93 percent predicted FEV1 | Standard Deviation 3.35 |
| CHF 10067 2000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 56 | -0.68 percent predicted FEV1 | Standard Deviation 3.54 |
| CHF 10067 2000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 84 | 0.36 percent predicted FEV1 | Standard Deviation 4.3 |
| CHF 10067 2000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 7 | 0.50 percent predicted FEV1 | Standard Deviation 2.74 |
| CHF 10067 2000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 28 | -0.55 percent predicted FEV1 | Standard Deviation 3.06 |
| CHF 10067 3000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 84 | -2.70 percent predicted FEV1 | Standard Deviation 2.93 |
| CHF 10067 3000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 28 | -2.93 percent predicted FEV1 | Standard Deviation 2.81 |
| CHF 10067 3000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 7 | -0.20 percent predicted FEV1 | Standard Deviation 1.34 |
| CHF 10067 3000 mg (Test Treatment) | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 56 | -0.75 percent predicted FEV1 | Standard Deviation 5.68 |
| Placebo | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 84 | -1.40 percent predicted FEV1 | Standard Deviation 3.62 |
| Placebo | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 56 | -1.35 percent predicted FEV1 | Standard Deviation 2.93 |
| Placebo | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 7 | -0.43 percent predicted FEV1 | Standard Deviation 2.6 |
| Placebo | 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline | Day 28 | -0.55 percent predicted FEV1 | Standard Deviation 3.37 |
Secondary
12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline
Forced vital capacity (FVC) parameters will be summarised using descriptive statistics at each analysis time point by treatment. Summary results show the change from baseline of the percent predicted.
Time frame: Text adjusted Pre-dose (baseline), and on 7, 28, 56, and 84 day post-dose.
Population: Safety set: all subjects who were randomised and received a dose of study treatment, including partial dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 7 | 3.12 percent predicted FVC | Standard Deviation 2.24 |
| CHF 10067 1000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 28 | 2.70 percent predicted FVC | Standard Deviation 3.74 |
| CHF 10067 1000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 56 | 2.50 percent predicted FVC | Standard Deviation 1.87 |
| CHF 10067 1000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 84 | -0.72 percent predicted FVC | Standard Deviation 4.02 |
| CHF 10067 2000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 28 | -0.50 percent predicted FVC | Standard Deviation 2.58 |
| CHF 10067 2000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 84 | -0.36 percent predicted FVC | Standard Deviation 3.56 |
| CHF 10067 2000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 7 | -0.90 percent predicted FVC | Standard Deviation 3.31 |
| CHF 10067 2000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 56 | -1.17 percent predicted FVC | Standard Deviation 3.12 |
| CHF 10067 3000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 56 | -1.42 percent predicted FVC | Standard Deviation 6.55 |
| CHF 10067 3000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 84 | -1.98 percent predicted FVC | Standard Deviation 3.79 |
| CHF 10067 3000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 7 | -0.50 percent predicted FVC | Standard Deviation 2.89 |
| CHF 10067 3000 mg (Test Treatment) | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 28 | -3.23 percent predicted FVC | Standard Deviation 2.76 |
| Placebo | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 84 | -1.97 percent predicted FVC | Standard Deviation 3.22 |
| Placebo | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 7 | -0.92 percent predicted FVC | Standard Deviation 3.8 |
| Placebo | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 28 | -0.13 percent predicted FVC | Standard Deviation 4.1 |
| Placebo | 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline | Day 56 | -0.90 percent predicted FVC | Standard Deviation 2.84 |
Secondary
13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure
Evaluate abnormal changes in systolic and diastolic blood pressure from baseline at any post-baseline time point.
Time frame: From pre-dose (baseline) up to day 84.
Population: Safety set: all subjects who were randomised and received a dose of study treatment, including partial dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure Decrease From Baseline >20 mmHg | 3 Participants |
| CHF 10067 1000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure Decrease From Baseline >10 mmHg | 3 Participants |
| CHF 10067 1000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure Increase From Baseline >10 mmHg | 2 Participants |
| CHF 10067 1000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure Increase From Baseline >20 mmHg | 1 Participants |
| CHF 10067 2000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure Increase From Baseline >20 mmHg | 0 Participants |
| CHF 10067 2000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure Increase From Baseline >10 mmHg | 2 Participants |
| CHF 10067 2000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure Decrease From Baseline >10 mmHg | 5 Participants |
| CHF 10067 2000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure Decrease From Baseline >20 mmHg | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure Decrease From Baseline >10 mmHg | 5 Participants |
| CHF 10067 3000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure Increase From Baseline >10 mmHg | 2 Participants |
| CHF 10067 3000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure Increase From Baseline >20 mmHg | 1 Participants |
| CHF 10067 3000 mg (Test Treatment) | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure Decrease From Baseline >20 mmHg | 1 Participants |
| Placebo | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure Increase From Baseline >10 mmHg | 3 Participants |
| Placebo | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure Decrease From Baseline >20 mmHg | 2 Participants |
| Placebo | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Systolic Blood Pressure Increase From Baseline >20 mmHg | 2 Participants |
| Placebo | 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure | Diastolic Blood Pressure Decrease From Baseline >10 mmHg | 4 Participants |
Secondary
14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb).
Evaluate the immunogenicity profile of CHF 10067 in serum, with respect to the development of anti-drug antibody (ADA) and neutralising antibody (nAb). A robust immunogenicity profile indicates the potential for the drug to trigger an immune response in patients, leading to the formation of ADAs. These antibodies can affect the drug's efficacy, safety, and pharmacokinetics. Detecting the presence of ADAs in serum samples was performed using an enzyme linked immunosorbent assay (ELISA), a validated assay method. Neutralizing Antibody (nAb) are a subset of ADAs that can interfere with the drug's therapeutic activity by blocking its binding to the target or inhibiting its downstream effects. The presence of ADAs and nAbs can affect the drug's pharmacokinetics (PK) by altering its absorption, distribution, metabolism, and excretion. This can lead to changes in drug exposure and potentially impact efficacy and safety.
Time frame: Pre-dose (baseline), at day 14, 28, 56, 84, and in case of early termination.
Population: Safety set: all subjects who were randomised and received a dose of study treatment, including partial dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 4_Duration of ADA Persistently positive ADA | 0 Participants |
| CHF 10067 1000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 7_nAb positive at any visit | 1 Participants |
| CHF 10067 1000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 6_Treatment-boosted ADA | 0 Participants |
| CHF 10067 1000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 3_ADA incidence (ADA+) | 1 Participants |
| CHF 10067 1000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 2_ADA prevalence | 1 Participants |
| CHF 10067 1000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 1_Baseline ADA positive | 0 Participants |
| CHF 10067 1000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 5_Duration of ADA Transiently positive ADA | 1 Participants |
| CHF 10067 2000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 3_ADA incidence (ADA+) | 0 Participants |
| CHF 10067 2000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 4_Duration of ADA Persistently positive ADA | 0 Participants |
| CHF 10067 2000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 5_Duration of ADA Transiently positive ADA | 0 Participants |
| CHF 10067 2000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 6_Treatment-boosted ADA | 0 Participants |
| CHF 10067 2000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 7_nAb positive at any visit | 0 Participants |
| CHF 10067 2000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 1_Baseline ADA positive | 0 Participants |
| CHF 10067 2000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 2_ADA prevalence | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 7_nAb positive at any visit | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 4_Duration of ADA Persistently positive ADA | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 3_ADA incidence (ADA+) | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 1_Baseline ADA positive | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 2_ADA prevalence | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 6_Treatment-boosted ADA | 0 Participants |
| CHF 10067 3000 mg (Test Treatment) | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 5_Duration of ADA Transiently positive ADA | 0 Participants |
| Placebo | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 6_Treatment-boosted ADA | 0 Participants |
| Placebo | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 2_ADA prevalence | 0 Participants |
| Placebo | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 7_nAb positive at any visit | 0 Participants |
| Placebo | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 4_Duration of ADA Persistently positive ADA | 0 Participants |
| Placebo | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 3_ADA incidence (ADA+) | 0 Participants |
| Placebo | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 1_Baseline ADA positive | 0 Participants |
| Placebo | 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb). | 5_Duration of ADA Transiently positive ADA | 0 Participants |
Secondary
2_Systemic Exposure [Area Under the Concentration-time Curve From Zero to Time (AUC0-t)]
Evaluate the area under the concentration-time curve (AUC) from zero to the last quantifiable concentration (AUC0-t) of CHF10067 after a single dose.
Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.
Population: Pharmacokinetic set (PK set): all subjects from the safety set, excluding subjects without any valid PK measurement or with important protocol deviations significantly affecting PK, for example, use of non-permitted medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 2_Systemic Exposure [Area Under the Concentration-time Curve From Zero to Time (AUC0-t)] | 3424 day.μg/mL | Standard Deviation 647 |
| CHF 10067 2000 mg (Test Treatment) | 2_Systemic Exposure [Area Under the Concentration-time Curve From Zero to Time (AUC0-t)] | 7902 day.μg/mL | Standard Deviation 1001 |
| CHF 10067 3000 mg (Test Treatment) | 2_Systemic Exposure [Area Under the Concentration-time Curve From Zero to Time (AUC0-t)] | 15592 day.μg/mL | Standard Deviation 3027 |
Secondary
3_Area Under the Concentration-time Curve (AUC) From Zero to Infinity (AUC0-∞)
Evaluate the area under the concentration-time curve (AUC) from zero to infinity (AUC0-∞) of CHF10067 after a single dose.
Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.
Population: Pharmacokinetic set (PK set): all subjects from the safety set, excluding subjects without any valid PK measurement or with important protocol deviations significantly affecting PK, for example, use of non-permitted medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 3_Area Under the Concentration-time Curve (AUC) From Zero to Infinity (AUC0-∞) | 3450 day.μg/mL | Standard Deviation 660 |
| CHF 10067 2000 mg (Test Treatment) | 3_Area Under the Concentration-time Curve (AUC) From Zero to Infinity (AUC0-∞) | 8141 day.μg/mL | Standard Deviation 1112 |
| CHF 10067 3000 mg (Test Treatment) | 3_Area Under the Concentration-time Curve (AUC) From Zero to Infinity (AUC0-∞) | 16328 day.μg/mL | Standard Deviation 3245 |
Secondary
4_Pharmacokinetics -- Maximum Plasma Concentration (Cmax)
Evaluate the Cmax (maximum observed concentration) after a single dose of CHF10067.
Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.
Population: Pharmacokinetic set (PK set): all subjects from the safety set, excluding subjects without any valid PK measurement or with important protocol deviations significantly affecting PK, for example, use of non-permitted medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 4_Pharmacokinetics -- Maximum Plasma Concentration (Cmax) | 307 μg/mL | Standard Deviation 43.9 |
| CHF 10067 2000 mg (Test Treatment) | 4_Pharmacokinetics -- Maximum Plasma Concentration (Cmax) | 668 μg/mL | Standard Deviation 126 |
| CHF 10067 3000 mg (Test Treatment) | 4_Pharmacokinetics -- Maximum Plasma Concentration (Cmax) | 1067 μg/mL | Standard Deviation 173 |
Secondary
5_Pharmacokinetics -- Time to Maximum Observed Concentration (Tmax)
Evaluate the time to maximum observed concentration (tmax).
Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.
Population: Pharmacokinetic set (PK set): all subjects from the safety set, excluding subjects without any valid PK measurement or with important protocol deviations significantly affecting PK, for example, use of non-permitted medications.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 5_Pharmacokinetics -- Time to Maximum Observed Concentration (Tmax) | 1.69 hour |
| CHF 10067 2000 mg (Test Treatment) | 5_Pharmacokinetics -- Time to Maximum Observed Concentration (Tmax) | 3.78 hour |
| CHF 10067 3000 mg (Test Treatment) | 5_Pharmacokinetics -- Time to Maximum Observed Concentration (Tmax) | 5.39 hour |
Secondary
6_Pharmacokinetics -- Serum Concentration at the End of Infusion (Cinf)
Evaluate serum concentration at the end of infusion (Cinf) of CHF10067.
Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion (up to 6 hours from the start of infusion).
Population: Pharmacokinetic set (PK set): all subjects from the safety set, excluding subjects without any valid PK measurement or with important protocol deviations significantly affecting PK, for example, use of non-permitted medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 6_Pharmacokinetics -- Serum Concentration at the End of Infusion (Cinf) | 304 μg/mL | Standard Deviation 44.6 |
| CHF 10067 2000 mg (Test Treatment) | 6_Pharmacokinetics -- Serum Concentration at the End of Infusion (Cinf) | 658 μg/mL | Standard Deviation 138 |
| CHF 10067 3000 mg (Test Treatment) | 6_Pharmacokinetics -- Serum Concentration at the End of Infusion (Cinf) | 1065 μg/mL | Standard Deviation 174 |
Secondary
7_Pharmacokinetics -- Time at the End of Infusion (Tinf)
Evaluate the time of serum concentration at the end of infusion (Tinf). Time at the end of the infusion.
Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion (up to 6 hours from the start of infusion).
Population: Pharmacokinetic set (PK set): all subjects from the safety set, excluding subjects without any valid PK measurement or with important protocol deviations significantly affecting PK, for example, use of non-permitted medications.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 7_Pharmacokinetics -- Time at the End of Infusion (Tinf) | 1.68 hour |
| CHF 10067 2000 mg (Test Treatment) | 7_Pharmacokinetics -- Time at the End of Infusion (Tinf) | 3.69 hour |
| CHF 10067 3000 mg (Test Treatment) | 7_Pharmacokinetics -- Time at the End of Infusion (Tinf) | 5.38 hour |
Secondary
8_Pharmacokinetics -- Clearance (CL)
Evaluate clearance (CL) of CHF10067.
Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.
Population: Pharmacokinetic set (PK set): all subjects from the safety set, excluding subjects without any valid PK measurement or with important protocol deviations significantly affecting PK, for example, use of non-permitted medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 8_Pharmacokinetics -- Clearance (CL) | 0.295 liter/day | Standard Deviation 0.0489 |
| CHF 10067 2000 mg (Test Treatment) | 8_Pharmacokinetics -- Clearance (CL) | 0.250 liter/day | Standard Deviation 0.0357 |
| CHF 10067 3000 mg (Test Treatment) | 8_Pharmacokinetics -- Clearance (CL) | 0.190 liter/day | Standard Deviation 0.0363 |
Secondary
9_Pharmacokinetics -- Volume of Distribution (Vz)
Evaluate volume of distribution (Vz) CHF10067.
Time frame: Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.
Population: Pharmacokinetic set (PK set): all subjects from the safety set, excluding subjects without any valid PK measurement or with important protocol deviations significantly affecting PK, for example, use of non-permitted medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CHF 10067 1000 mg (Test Treatment) | 9_Pharmacokinetics -- Volume of Distribution (Vz) | 4.93 liter | Standard Deviation 0.969 |
| CHF 10067 2000 mg (Test Treatment) | 9_Pharmacokinetics -- Volume of Distribution (Vz) | 5.99 liter | Standard Deviation 0.716 |
| CHF 10067 3000 mg (Test Treatment) | 9_Pharmacokinetics -- Volume of Distribution (Vz) | 5.21 liter | Standard Deviation 1.03 |