Healthy
Conditions
Keywords
Antithrombotic, Intrinsic coagulation pathway
Brief summary
The purpose of this First-in-Human study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of Ir-CPI, a novel dual inhibitor of FXIIa and FXIa, following IV administration of single ascending doses in healthy male volunteers.
Interventions
DRUGIr-CPI - Dose 2
6 participants received a single intravenous dose of 3.0 mg/kg of Ir-CPI during 6 hours
DRUGIr-CPI - Dose 3
6 participants received a single intravenous dose of 6.0 mg/kg of Ir-CPI during 6 hours
DRUGIr-CPI - Dose 1
6 participants received a single intravenous dose of 1.5 mg/kg of Ir-CPI during 6 hours
DRUGIr-CPI - Dose 4
6 participants received a single intravenous dose of 9.0 mg/kg of Ir-CPI during 6 hours
DRUGPlacebo
For each dose group, 2 additional participants received a single intravenous dose of placebo during 6 hours (8 in total).
Sponsors
Bioxodes S.A.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Participants must satisfy all of the following inclusion criteria before being allowed to enter the study: 1. Have given written informed consent approved by the relevant Ethics Committee (EC) governing the site, indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. 2. Male participants between 18 and 55 years of age, inclusive at screening. 3. Otherwise healthy with no clinically significant abnormalities as determined by medical history, physical examination, blood chemistry assessments, haematological assessments, coagulation and urinalysis, measurement of vital signs, and ECG. Isolated out-of-range values judged by the PI (or designated physician) to be of no clinical significance can be allowed. This determination must be recorded in the participant's source documents. 4. Have a body weight in the range of 50 to 90 kg inclusive at screening. Have a body mass index (BMI) of 19 to 28 kg/m2 inclusive at screening. 5. Agree to abstain from alcohol intake 24 hours before administration of study drug, during the in-patient period of the study and 24 hours prior to all other ambulatory visits, up until and including the discharge visit. 6. Agree not to use prescription medications within 14 days prior to study drug administration and through the duration of the study, unless approved by the PI and Sponsor medical monitor. 7. Non-smokers or abstinence from tobacco or nicotine-containing products for at least 3 months prior to screening. 8. Agree not to use over-the-counter (OTC) medications \[including decongestants, antihistamines, and herbal medication (including herbal tea and St. John's Wort)\], within 14 days prior to study drug administration through the discharge visit, unless approved by the PI and Sponsor medical monitor. Occasional use of paracetamol at recommended doses is allowed. Special rules apply for aspirin, corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDS (see
Exclusion criteria
6-7-8-9) 9. Venous access (both arms) sufficient to allow blood sampling and study drug administration as per protocol. 10. Participants and their partners of childbearing potential \[meaning who are not surgically sterile (tubal ligation/obstruction or removal of ovaries or uterus) or post-menopausal (absence of menstrual periods for at least 12 consecutive months)\] must be willing to use 2 methods of contraception: - a highly effective method of birth control starting at screening. Highly effective methods of birth control are defined as those that result in a low failure rate (i.e. Pearl Index less than 1% per year) when used consistently and correctly, such as implants, rings, patches, injectable or combined oral contraceptives, intrauterine devices (IUDs), or sexual abstinence (periodic abstinence e.g. calendar, ovulation, symptothermal, postovulation methods, declaration of abstinence for the duration of the trial, and withdrawal are not acceptable methods of contraception) . - and a local barrier form of contraception. Acceptable barrier methods are either the participant's use of a condom or the partner's use of an occlusive cap or diaphragm, or spermicides. Participants will not donate sperm from the selection visit and up to 90 days after the infusion. In case of sterile or vasectomised participants, no contraception will be required for their partners of childbearing potential. 11. Willing/able to adhere to the study visit schedule and other requirements, prohibitions and restrictions specified in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | At pre-dose (baseline), 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose and at the discharge visit (Day 10 ± 2 days) | These safety aPTT results were readily available to the PI for safety follow-up during and after the study drug administration. Safety aPTT was followed up at the bedside at regular time-points (as opposed to the PD biomarker aPTT, which was assessed by the central laboratory alongside the PK time-points). An aPTT ratio was calculated by dividing the aPTT value (in sec) of the specific time-point (aPTTt) by the baseline aPTT value (in sec) (aPTTbaseline) of the same participant (aPTT ratio = aPTTt/aPTTbaseline). The baseline time-point was considered as having an aPTT ratio of 1. Concerning the row titles, for example, Day 1 H02:00 corresponds to aPTT ratio results obtained on Day 1, 2 hours after the start of the infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of the Time to Reach Maximum Plasma Concentration (Tmax) of Ir-CPI | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only) | — |
| Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf) | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only) | — |
| Measurement of the Maximum Plasma Concentration (Cmax) of Ir-CPI | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only) | — |
| Measurement of the Effect of Ir-CPI on Factor XI Activity | Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days) | The method is a clotting assay where all the clotting factors are present (constant and in excess, brought by the deficient plasma), excepted for FXI, which is brought by the diluted tested plasma, and clotting is triggered with cephalin, activator and calcium (aPTT). FXI is the limiting factor and clotting time is inversely proportional to the concentration of FXI. There is an inverse linear relationship between the percentage of FXI activity and the corresponding clotting time. Central laboratory normal ranges for Factor XI activity are between 65 and 150 %. Concerning the row titles, for example, Day 1 H02:00 corresponds to the percentage of FXI activity obtained on Day 1, 2 hours after the start of the infusion. |
| Measurement of the Effect of Ir-CPI on Factor XII Activity | Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days) | The method is a clotting assay where all the clotting factors are present (constant and in excess, brought by the deficient plasma), excepted for FXII, which is brought by the diluted tested plasma, and clotting is triggered with cephalin, activator and calcium (aPTT). FXII is the limiting factor and clotting time is inversely proportional to the concentration of FXII. There is an inverse linear relationship between the percentage of FXII activity and the corresponding clotting time. Central laboratory normal ranges for Factor XII activity are between 50 and 150 %. Concerning the row titles, for example, Day 1 H02:00 corresponds to the percentage of FXII activity obtained on Day 1, 2 hours after the start of the infusion. |
| Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days) | The activated partial thromboplastin time (aPTT) is used as a pharmacodynamic marker. No data were available for the Ir-CPI 1.5 mg/kg group because the results were not usable due to plasma preparation and method repeatability problems. An aPTT ratio was calculated by dividing the aPTT value (in sec) of the specific time-point (aPTTt) by the baseline aPTT value (in sec) (aPTTbaseline) of the same participant (aPTT ratio = aPTTt/aPTTbaseline). The baseline time-point (Day 1 H00:00) was considered as having an aPTT ratio of 1. Concerning the row titles, for example, Day 1 H02:00 corresponds to aPTT ratio results obtained on Day 1, 2 hours after the start of the infusion. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ir-CPI - Dose 1 Ir-CPI - Dose 1: 6 participants received a single intravenous dose of 1.5 mg/kg of Ir-CPI during 6 hours | 6 |
| Ir-CPI - Dose 2 Ir-CPI - Dose 2: 6 participants received a single intravenous dose of 3.0 mg/kg of Ir-CPI during 6 hours | 6 |
| Ir-CPI - Dose 3 Ir-CPI - Dose 3: 6 participants received a single intravenous dose of 6.0 mg/kg of Ir-CPI during 6 hours | 6 |
| Ir-CPI - Dose 4 Ir-CPI - Dose 4: 6 participants received a single intravenous dose of 9.0 mg/kg of Ir-CPI during 6 hours | 6 |
| Placebo For each dose group, 2 additional participants received a single intravenous dose of placebo during 6 hours (8 in total). | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | Ir-CPI - Dose 1 | Ir-CPI - Dose 2 | Ir-CPI - Dose 3 | Ir-CPI - Dose 4 | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants | 32 Participants |
| Age, Continuous | 36.0 years STANDARD_DEVIATION 12.2 | 35.2 years STANDARD_DEVIATION 11.8 | 27.3 years STANDARD_DEVIATION 7.6 | 34.8 years STANDARD_DEVIATION 10 | 35.8 years STANDARD_DEVIATION 11.4 | 33.9 years STANDARD_DEVIATION 10.6 |
| Body Mass Index (BMI) | 24.52 kg/m² STANDARD_DEVIATION 0.95 | 24.75 kg/m² STANDARD_DEVIATION 2.47 | 24.65 kg/m² STANDARD_DEVIATION 2.32 | 21.81 kg/m² STANDARD_DEVIATION 1.63 | 22.68 kg/m² STANDARD_DEVIATION 2.23 | 23.62 kg/m² STANDARD_DEVIATION 2.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 178.8 cm STANDARD_DEVIATION 4.4 | 175.3 cm STANDARD_DEVIATION 4.5 | 177.2 cm STANDARD_DEVIATION 4.9 | 174.8 cm STANDARD_DEVIATION 6.8 | 179.5 cm STANDARD_DEVIATION 6.9 | 177.3 cm STANDARD_DEVIATION 5.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants | 32 Participants |
| Region of Enrollment Belgium | 6 participants | 6 participants | 6 participants | 6 participants | 8 participants | 32 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 8 Participants | 32 Participants |
| Weight | 78.43 kg STANDARD_DEVIATION 4.28 | 76.22 kg STANDARD_DEVIATION 9.24 | 77.25 kg STANDARD_DEVIATION 6.34 | 66.80 kg STANDARD_DEVIATION 7.93 | 72.96 kg STANDARD_DEVIATION 6.99 | 74.25 kg STANDARD_DEVIATION 7.84 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 4 / 6 | 5 / 6 | 5 / 6 | 6 / 6 | 7 / 8 |
| serious Total, serious adverse events | 1 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 8 |
Outcome results
Primary
Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT)
These safety aPTT results were readily available to the PI for safety follow-up during and after the study drug administration. Safety aPTT was followed up at the bedside at regular time-points (as opposed to the PD biomarker aPTT, which was assessed by the central laboratory alongside the PK time-points). An aPTT ratio was calculated by dividing the aPTT value (in sec) of the specific time-point (aPTTt) by the baseline aPTT value (in sec) (aPTTbaseline) of the same participant (aPTT ratio = aPTTt/aPTTbaseline). The baseline time-point was considered as having an aPTT ratio of 1. Concerning the row titles, for example, Day 1 H02:00 corresponds to aPTT ratio results obtained on Day 1, 2 hours after the start of the infusion.
Time frame: At pre-dose (baseline), 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose and at the discharge visit (Day 10 ± 2 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ir-CPI - Dose 1 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H04:00 | 1.768 aPTT ratio | Standard Deviation 0.123 |
| Ir-CPI - Dose 1 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 10 (discharge visit) | 1.003 aPTT ratio | Standard Deviation 0.029 |
| Ir-CPI - Dose 1 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:00 | 1.860 aPTT ratio | Standard Deviation 0.103 |
| Ir-CPI - Dose 1 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 4 H72:00 | 1.020 aPTT ratio | Standard Deviation 0.036 |
| Ir-CPI - Dose 1 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 3 H48:00 | 1.033 aPTT ratio | Standard Deviation 0.041 |
| Ir-CPI - Dose 1 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H02:00 | 1.600 aPTT ratio | Standard Deviation 0.08 |
| Ir-CPI - Dose 1 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:00 (baseline) | 1.000 aPTT ratio | Standard Deviation 0 |
| Ir-CPI - Dose 1 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 2 H24:00 | 1.162 aPTT ratio | Standard Deviation 0.056 |
| Ir-CPI - Dose 1 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H12:00 | 1.308 aPTT ratio | Standard Deviation 0.07 |
| Ir-CPI - Dose 1 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H08:00 | 1.520 aPTT ratio | Standard Deviation 0.1 |
| Ir-CPI - Dose 2 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H02:00 | 1.978 aPTT ratio | Standard Deviation 0.068 |
| Ir-CPI - Dose 2 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:00 (baseline) | 1.000 aPTT ratio | Standard Deviation 0 |
| Ir-CPI - Dose 2 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H04:00 | 2.262 aPTT ratio | Standard Deviation 0.085 |
| Ir-CPI - Dose 2 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:00 | 2.313 aPTT ratio | Standard Deviation 0.06 |
| Ir-CPI - Dose 2 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H08:00 | 1.832 aPTT ratio | Standard Deviation 0.072 |
| Ir-CPI - Dose 2 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H12:00 | 1.600 aPTT ratio | Standard Deviation 0.102 |
| Ir-CPI - Dose 2 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 2 H24:00 | 1.352 aPTT ratio | Standard Deviation 0.122 |
| Ir-CPI - Dose 2 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 3 H48:00 | 1.123 aPTT ratio | Standard Deviation 0.132 |
| Ir-CPI - Dose 2 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 4 H72:00 | 1.083 aPTT ratio | Standard Deviation 0.056 |
| Ir-CPI - Dose 2 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 10 (discharge visit) | 1.017 aPTT ratio | Standard Deviation 0.072 |
| Ir-CPI - Dose 3 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H12:00 | 1.848 aPTT ratio | Standard Deviation 0.075 |
| Ir-CPI - Dose 3 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 4 H72:00 | 1.143 aPTT ratio | Standard Deviation 0.067 |
| Ir-CPI - Dose 3 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H04:00 | 2.628 aPTT ratio | Standard Deviation 0.26 |
| Ir-CPI - Dose 3 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:00 | 2.775 aPTT ratio | Standard Deviation 0.269 |
| Ir-CPI - Dose 3 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H02:00 | 2.405 aPTT ratio | Standard Deviation 0.214 |
| Ir-CPI - Dose 3 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H08:00 | 2.135 aPTT ratio | Standard Deviation 0.208 |
| Ir-CPI - Dose 3 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 2 H24:00 | 1.627 aPTT ratio | Standard Deviation 0.114 |
| Ir-CPI - Dose 3 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:00 (baseline) | 1.000 aPTT ratio | Standard Deviation 0 |
| Ir-CPI - Dose 3 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 10 (discharge visit) | 1.027 aPTT ratio | Standard Deviation 0.046 |
| Ir-CPI - Dose 3 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 3 H48:00 | 1.313 aPTT ratio | Standard Deviation 0.063 |
| Ir-CPI - Dose 4 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H02:00 | 2.627 aPTT ratio | Standard Deviation 0.126 |
| Ir-CPI - Dose 4 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 10 (discharge visit) | 0.993 aPTT ratio | Standard Deviation 0.043 |
| Ir-CPI - Dose 4 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:00 (baseline) | 1.000 aPTT ratio | Standard Deviation 0 |
| Ir-CPI - Dose 4 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H04:00 | 2.875 aPTT ratio | Standard Deviation 0.129 |
| Ir-CPI - Dose 4 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H12:00 | 2.077 aPTT ratio | Standard Deviation 0.046 |
| Ir-CPI - Dose 4 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 3 H48:00 | 1.377 aPTT ratio | Standard Deviation 0.064 |
| Ir-CPI - Dose 4 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 4 H72:00 | 1.182 aPTT ratio | Standard Deviation 0.046 |
| Ir-CPI - Dose 4 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 2 H24:00 | 1.725 aPTT ratio | Standard Deviation 0.056 |
| Ir-CPI - Dose 4 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:00 | 2.993 aPTT ratio | Standard Deviation 0.196 |
| Ir-CPI - Dose 4 | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H08:00 | 2.367 aPTT ratio | Standard Deviation 0.096 |
| Placebo | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:00 | 0.994 aPTT ratio | Standard Deviation 0.086 |
| Placebo | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 4 H72:00 | 0.974 aPTT ratio | Standard Deviation 0.071 |
| Placebo | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H08:00 | 0.960 aPTT ratio | Standard Deviation 0.091 |
| Placebo | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H12:00 | 0.970 aPTT ratio | Standard Deviation 0.075 |
| Placebo | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 10 (discharge visit) | 0.993 aPTT ratio | Standard Deviation 0.093 |
| Placebo | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 2 H24:00 | 0.973 aPTT ratio | Standard Deviation 0.077 |
| Placebo | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:00 (baseline) | 1.000 aPTT ratio | Standard Deviation 0 |
| Placebo | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 3 H48:00 | 0.983 aPTT ratio | Standard Deviation 0.108 |
| Placebo | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H04:00 | 0.981 aPTT ratio | Standard Deviation 0.077 |
| Placebo | Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT) | Day 1 H02:00 | 0.986 aPTT ratio | Standard Deviation 0.088 |
Secondary
Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf)
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only)
Population: Pharmacokinetic set (PKS): all of the included participants who were administered a complete infusion of study drug without major protocol deviation affecting PK evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ir-CPI - Dose 1 | Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf) | AUC0-6h | 3648.0 h*ng/mL | Standard Deviation 250.7 |
| Ir-CPI - Dose 1 | Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf) | AUC0-inf | 13446.3 h*ng/mL | Standard Deviation 1208.2 |
| Ir-CPI - Dose 2 | Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf) | AUC0-inf | 26573.3 h*ng/mL | Standard Deviation 2037.3 |
| Ir-CPI - Dose 2 | Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf) | AUC0-6h | 7915.5 h*ng/mL | Standard Deviation 1210.2 |
| Ir-CPI - Dose 3 | Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf) | AUC0-6h | 15184.7 h*ng/mL | Standard Deviation 1863.9 |
| Ir-CPI - Dose 3 | Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf) | AUC0-inf | 53541.5 h*ng/mL | Standard Deviation 3832.6 |
| Ir-CPI - Dose 4 | Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf) | AUC0-6h | 24683.2 h*ng/mL | Standard Deviation 5069.5 |
| Ir-CPI - Dose 4 | Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf) | AUC0-inf | 104509.8 h*ng/mL | Standard Deviation 10124.8 |
Secondary
Measurement of the Effect of Ir-CPI on Factor XI Activity
The method is a clotting assay where all the clotting factors are present (constant and in excess, brought by the deficient plasma), excepted for FXI, which is brought by the diluted tested plasma, and clotting is triggered with cephalin, activator and calcium (aPTT). FXI is the limiting factor and clotting time is inversely proportional to the concentration of FXI. There is an inverse linear relationship between the percentage of FXI activity and the corresponding clotting time. Central laboratory normal ranges for Factor XI activity are between 65 and 150 %. Concerning the row titles, for example, Day 1 H02:00 corresponds to the percentage of FXI activity obtained on Day 1, 2 hours after the start of the infusion.
Time frame: Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days)
Population: This analysis was performed on the Pharmacodyamic Set (PDS): all of the included participants who completed the study without any protocol deviation affecting PD evaluation and with at least one available post-baseline PD data point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H10:00 | 99.3 Percentage of Factor XI activity | Standard Deviation 28.1 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H00:30 | 98.7 Percentage of Factor XI activity | Standard Deviation 20.1 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H04:00 | 88.8 Percentage of Factor XI activity | Standard Deviation 19.1 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H00:00 (baseline) | 112.3 Percentage of Factor XI activity | Standard Deviation 23.9 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 2 H24:00 | 116.0 Percentage of Factor XI activity | Standard Deviation 35.8 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H08:00 | 92.8 Percentage of Factor XI activity | Standard Deviation 20.8 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H02:00 | 91.5 Percentage of Factor XI activity | Standard Deviation 19.1 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H07:00 | 91.3 Percentage of Factor XI activity | Standard Deviation 25.9 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H06:00 | 85.5 Percentage of Factor XI activity | Standard Deviation 16.5 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H07:30 | 91.7 Percentage of Factor XI activity | Standard Deviation 23.9 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 5 H96:00 | 110.8 Percentage of Factor XI activity | Standard Deviation 23 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 4 H72:00 | 136.8 Percentage of Factor XI activity | Standard Deviation 81 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H12:00 | 102.7 Percentage of Factor XI activity | Standard Deviation 25 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H01:00 | 94.8 Percentage of Factor XI activity | Standard Deviation 23.4 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H06:30 | 88.7 Percentage of Factor XI activity | Standard Deviation 19.5 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H16:00 | 101.8 Percentage of Factor XI activity | Standard Deviation 25.7 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 3 H48:00 | 117.8 Percentage of Factor XI activity | Standard Deviation 21.9 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 10 (discharge visit) | 111.3 Percentage of Factor XI activity | Standard Deviation 28.6 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H01:30 | 98.0 Percentage of Factor XI activity | Standard Deviation 18.2 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 10 (discharge visit) | 107.7 Percentage of Factor XI activity | Standard Deviation 17.9 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 3 H48:00 | 104.7 Percentage of Factor XI activity | Standard Deviation 24.8 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H08:00 | 73.8 Percentage of Factor XI activity | Standard Deviation 12 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H10:00 | 83.2 Percentage of Factor XI activity | Standard Deviation 14.5 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H01:00 | 79.5 Percentage of Factor XI activity | Standard Deviation 14.3 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H12:00 | 87.0 Percentage of Factor XI activity | Standard Deviation 16.1 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H16:00 | 89.0 Percentage of Factor XI activity | Standard Deviation 15.2 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H01:30 | 73.3 Percentage of Factor XI activity | Standard Deviation 11.3 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 5 H96:00 | 105.5 Percentage of Factor XI activity | Standard Deviation 24.2 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H02:00 | 70.8 Percentage of Factor XI activity | Standard Deviation 12.8 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 2 H24:00 | 92.7 Percentage of Factor XI activity | Standard Deviation 15.8 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H04:00 | 64.0 Percentage of Factor XI activity | Standard Deviation 10.8 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H00:00 (baseline) | 103.7 Percentage of Factor XI activity | Standard Deviation 22.2 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H06:00 | 61.7 Percentage of Factor XI activity | Standard Deviation 12.3 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H00:30 | 85.5 Percentage of Factor XI activity | Standard Deviation 15.6 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 4 H72:00 | 104.5 Percentage of Factor XI activity | Standard Deviation 20.9 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H06:30 | 67.7 Percentage of Factor XI activity | Standard Deviation 10.8 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H07:00 | 70.7 Percentage of Factor XI activity | Standard Deviation 13.9 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H07:30 | 74.5 Percentage of Factor XI activity | Standard Deviation 11.7 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H04:00 | 42.5 Percentage of Factor XI activity | Standard Deviation 5.5 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H07:30 | 51.0 Percentage of Factor XI activity | Standard Deviation 5.6 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H07:00 | 49.2 Percentage of Factor XI activity | Standard Deviation 4.4 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H06:00 | 41.3 Percentage of Factor XI activity | Standard Deviation 3.3 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H00:00 (baseline) | 89.2 Percentage of Factor XI activity | Standard Deviation 9.8 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 3 H48:00 | 85.8 Percentage of Factor XI activity | Standard Deviation 13.8 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H12:00 | 61.5 Percentage of Factor XI activity | Standard Deviation 7.1 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H08:00 | 54.8 Percentage of Factor XI activity | Standard Deviation 4.3 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H06:30 | 49.5 Percentage of Factor XI activity | Standard Deviation 6.7 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H00:30 | 61.8 Percentage of Factor XI activity | Standard Deviation 8.3 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 2 H24:00 | 73.2 Percentage of Factor XI activity | Standard Deviation 9.9 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H16:00 | 65.3 Percentage of Factor XI activity | Standard Deviation 8 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H02:00 | 46.2 Percentage of Factor XI activity | Standard Deviation 6 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 10 (discharge visit) | 93.2 Percentage of Factor XI activity | Standard Deviation 9.3 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 5 H96:00 | 90.0 Percentage of Factor XI activity | Standard Deviation 11 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H01:30 | 49.8 Percentage of Factor XI activity | Standard Deviation 6.3 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 4 H72:00 | 92.8 Percentage of Factor XI activity | Standard Deviation 6.9 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H01:00 | 53.3 Percentage of Factor XI activity | Standard Deviation 7.1 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H10:00 | 61.0 Percentage of Factor XI activity | Standard Deviation 6.9 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 4 H72:00 | 86.7 Percentage of Factor XI activity | Standard Deviation 17.3 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H00:00 (baseline) | 94.5 Percentage of Factor XI activity | Standard Deviation 8.4 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H16:00 | 63.5 Percentage of Factor XI activity | Standard Deviation 11 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H00:30 | 58.8 Percentage of Factor XI activity | Standard Deviation 8.1 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H01:00 | 54.7 Percentage of Factor XI activity | Standard Deviation 7.6 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H01:30 | 50.0 Percentage of Factor XI activity | Standard Deviation 7.6 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H02:00 | 47.2 Percentage of Factor XI activity | Standard Deviation 7.2 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H12:00 | 59.5 Percentage of Factor XI activity | Standard Deviation 9.7 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H04:00 | 41.7 Percentage of Factor XI activity | Standard Deviation 4.1 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H06:00 | 40.5 Percentage of Factor XI activity | Standard Deviation 5.5 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H06:30 | 45.3 Percentage of Factor XI activity | Standard Deviation 7 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H07:00 | 47.0 Percentage of Factor XI activity | Standard Deviation 8.4 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H07:30 | 47.8 Percentage of Factor XI activity | Standard Deviation 8 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H08:00 | 50.7 Percentage of Factor XI activity | Standard Deviation 9.1 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H10:00 | 56.7 Percentage of Factor XI activity | Standard Deviation 11.2 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 2 H24:00 | 71.2 Percentage of Factor XI activity | Standard Deviation 11.3 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 3 H48:00 | 81.5 Percentage of Factor XI activity | Standard Deviation 12.7 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 5 H96:00 | 97.2 Percentage of Factor XI activity | Standard Deviation 19.1 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 10 (discharge visit) | 99.3 Percentage of Factor XI activity | Standard Deviation 16.8 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H07:30 | 100.5 Percentage of Factor XI activity | Standard Deviation 14.5 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H07:00 | 101.6 Percentage of Factor XI activity | Standard Deviation 10.9 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H00:00 (baseline) | 95.9 Percentage of Factor XI activity | Standard Deviation 12.4 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 3 H48:00 | 104.0 Percentage of Factor XI activity | Standard Deviation 9.5 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H06:30 | 104.9 Percentage of Factor XI activity | Standard Deviation 13 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H06:00 | 106.6 Percentage of Factor XI activity | Standard Deviation 12.7 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H12:00 | 101.0 Percentage of Factor XI activity | Standard Deviation 11.5 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H02:00 | 100.1 Percentage of Factor XI activity | Standard Deviation 10.8 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 4 H72:00 | 105.5 Percentage of Factor XI activity | Standard Deviation 7.8 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H04:00 | 106.6 Percentage of Factor XI activity | Standard Deviation 13.8 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H01:30 | 99.3 Percentage of Factor XI activity | Standard Deviation 14.2 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H16:00 | 98.4 Percentage of Factor XI activity | Standard Deviation 11.1 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 10 (discharge visit) | 103.4 Percentage of Factor XI activity | Standard Deviation 11.7 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 5 H96:00 | 107.4 Percentage of Factor XI activity | Standard Deviation 14 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H01:00 | 104.8 Percentage of Factor XI activity | Standard Deviation 12.2 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H10:00 | 106.4 Percentage of Factor XI activity | Standard Deviation 14.9 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H00:30 | 99.5 Percentage of Factor XI activity | Standard Deviation 10.2 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 2 H24:00 | 104.8 Percentage of Factor XI activity | Standard Deviation 8.5 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XI Activity | Day 1 H08:00 | 106.4 Percentage of Factor XI activity | Standard Deviation 15.4 |
Secondary
Measurement of the Effect of Ir-CPI on Factor XII Activity
The method is a clotting assay where all the clotting factors are present (constant and in excess, brought by the deficient plasma), excepted for FXII, which is brought by the diluted tested plasma, and clotting is triggered with cephalin, activator and calcium (aPTT). FXII is the limiting factor and clotting time is inversely proportional to the concentration of FXII. There is an inverse linear relationship between the percentage of FXII activity and the corresponding clotting time. Central laboratory normal ranges for Factor XII activity are between 50 and 150 %. Concerning the row titles, for example, Day 1 H02:00 corresponds to the percentage of FXII activity obtained on Day 1, 2 hours after the start of the infusion.
Time frame: Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days)
Population: This analysis was performed on the Pharmacodyamic Set (PDS): all of the included participants who completed the study without any protocol deviation affecting PD evaluation and with at least one available post-baseline PD data point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 3 H48:00 | 128.7 Percentage of Factor XII activity | Standard Deviation 27.6 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H02:00 | 76.0 Percentage of Factor XII activity | Standard Deviation 16.3 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H00:00 (baseline) | 105.0 Percentage of Factor XII activity | Standard Deviation 24.9 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H00:30 | 93.0 Percentage of Factor XII activity | Standard Deviation 12.8 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H01:00 | 83.5 Percentage of Factor XII activity | Standard Deviation 21.2 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 2 H24:00 | 104.8 Percentage of Factor XII activity | Standard Deviation 25.9 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H04:00 | 68.5 Percentage of Factor XII activity | Standard Deviation 16.4 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 5 H96:00 | 123.5 Percentage of Factor XII activity | Standard Deviation 27.3 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H07:00 | 75.0 Percentage of Factor XII activity | Standard Deviation 21.1 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H08:00 | 77.7 Percentage of Factor XII activity | Standard Deviation 20.2 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H16:00 | 89.7 Percentage of Factor XII activity | Standard Deviation 23 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H06:00 | 64.8 Percentage of Factor XII activity | Standard Deviation 12.8 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 4 H72:00 | 121.5 Percentage of Factor XII activity | Standard Deviation 29.2 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H01:30 | 82.7 Percentage of Factor XII activity | Standard Deviation 23.6 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H07:30 | 75.2 Percentage of Factor XII activity | Standard Deviation 18.2 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H12:00 | 91.3 Percentage of Factor XII activity | Standard Deviation 21.6 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H06:30 | 69.5 Percentage of Factor XII activity | Standard Deviation 16.8 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 10 (discharge visit) | 122.0 Percentage of Factor XII activity | Standard Deviation 26.9 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H10:00 | 90.3 Percentage of Factor XII activity | Standard Deviation 22.9 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 5 H96:00 | 100.5 Percentage of Factor XII activity | Standard Deviation 17.4 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H07:00 | 47.0 Percentage of Factor XII activity | Standard Deviation 11 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H08:00 | 54.7 Percentage of Factor XII activity | Standard Deviation 12.1 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H07:30 | 53.3 Percentage of Factor XII activity | Standard Deviation 14.4 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H01:00 | 62.2 Percentage of Factor XII activity | Standard Deviation 17.7 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 10 (discharge visit) | 102.2 Percentage of Factor XII activity | Standard Deviation 20.2 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 4 H72:00 | 98.3 Percentage of Factor XII activity | Standard Deviation 15.9 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H01:30 | 53.3 Percentage of Factor XII activity | Standard Deviation 15 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 3 H48:00 | 96.7 Percentage of Factor XII activity | Standard Deviation 15.4 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H02:00 | 49.3 Percentage of Factor XII activity | Standard Deviation 12.5 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 2 H24:00 | 80.3 Percentage of Factor XII activity | Standard Deviation 16.4 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H04:00 | 40.5 Percentage of Factor XII activity | Standard Deviation 10.6 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H00:30 | 68.8 Percentage of Factor XII activity | Standard Deviation 18.7 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H16:00 | 73.8 Percentage of Factor XII activity | Standard Deviation 18.6 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H06:00 | 38.2 Percentage of Factor XII activity | Standard Deviation 5.7 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H00:00 (baseline) | 94.8 Percentage of Factor XII activity | Standard Deviation 20.8 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H12:00 | 71.3 Percentage of Factor XII activity | Standard Deviation 14.5 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H06:30 | 45.8 Percentage of Factor XII activity | Standard Deviation 11.8 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H10:00 | 65.5 Percentage of Factor XII activity | Standard Deviation 15.7 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H07:30 | 39.0 Percentage of Factor XII activity | Standard Deviation 17.1 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H00:00 (baseline) | 101.5 Percentage of Factor XII activity | Standard Deviation 36.9 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H00:30 | 60.8 Percentage of Factor XII activity | Standard Deviation 26.1 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H01:00 | 45.8 Percentage of Factor XII activity | Standard Deviation 21.7 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H01:30 | 43.8 Percentage of Factor XII activity | Standard Deviation 22.6 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H02:00 | 32.7 Percentage of Factor XII activity | Standard Deviation 13.7 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H04:00 | 27.5 Percentage of Factor XII activity | Standard Deviation 12.8 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H06:00 | 26.7 Percentage of Factor XII activity | Standard Deviation 11.9 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H06:30 | 33.3 Percentage of Factor XII activity | Standard Deviation 13.6 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H07:00 | 35.8 Percentage of Factor XII activity | Standard Deviation 14.7 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H08:00 | 44.3 Percentage of Factor XII activity | Standard Deviation 18.3 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H10:00 | 54.2 Percentage of Factor XII activity | Standard Deviation 21.7 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H12:00 | 58.5 Percentage of Factor XII activity | Standard Deviation 23.8 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H16:00 | 61.0 Percentage of Factor XII activity | Standard Deviation 24.2 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 2 H24:00 | 78.8 Percentage of Factor XII activity | Standard Deviation 31.3 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 3 H48:00 | 92.0 Percentage of Factor XII activity | Standard Deviation 35.8 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 4 H72:00 | 112.0 Percentage of Factor XII activity | Standard Deviation 13.3 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 5 H96:00 | 102.5 Percentage of Factor XII activity | Standard Deviation 36.5 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 10 (discharge visit) | 104.0 Percentage of Factor XII activity | Standard Deviation 35.3 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H06:30 | 25.8 Percentage of Factor XII activity | Standard Deviation 5.9 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H10:00 | 40.5 Percentage of Factor XII activity | Standard Deviation 8.8 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H06:00 | 24.2 Percentage of Factor XII activity | Standard Deviation 7.4 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 5 H96:00 | 100.2 Percentage of Factor XII activity | Standard Deviation 23.8 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H12:00 | 42.3 Percentage of Factor XII activity | Standard Deviation 9.7 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H04:00 | 24.8 Percentage of Factor XII activity | Standard Deviation 4.6 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H16:00 | 49.8 Percentage of Factor XII activity | Standard Deviation 11.7 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H02:00 | 26.3 Percentage of Factor XII activity | Standard Deviation 5 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 2 H24:00 | 59.3 Percentage of Factor XII activity | Standard Deviation 14.6 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H01:30 | 29.3 Percentage of Factor XII activity | Standard Deviation 5.3 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H00:00 (baseline) | 100.0 Percentage of Factor XII activity | Standard Deviation 15.9 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 3 H48:00 | 79.7 Percentage of Factor XII activity | Standard Deviation 21 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H01:00 | 35.0 Percentage of Factor XII activity | Standard Deviation 5.3 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 4 H72:00 | 89.5 Percentage of Factor XII activity | Standard Deviation 24.2 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H07:30 | 31.2 Percentage of Factor XII activity | Standard Deviation 8.1 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H07:00 | 29.8 Percentage of Factor XII activity | Standard Deviation 8.2 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H00:30 | 42.3 Percentage of Factor XII activity | Standard Deviation 9.7 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H08:00 | 34.0 Percentage of Factor XII activity | Standard Deviation 7.6 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 10 (discharge visit) | 107.2 Percentage of Factor XII activity | Standard Deviation 23.8 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H00:30 | 114.0 Percentage of Factor XII activity | Standard Deviation 29.6 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H08:00 | 117.4 Percentage of Factor XII activity | Standard Deviation 26.7 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H10:00 | 118.3 Percentage of Factor XII activity | Standard Deviation 24.3 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H06:00 | 116.4 Percentage of Factor XII activity | Standard Deviation 26.3 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H07:30 | 115.9 Percentage of Factor XII activity | Standard Deviation 25.5 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 3 H48:00 | 118.1 Percentage of Factor XII activity | Standard Deviation 28.6 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H01:00 | 119.1 Percentage of Factor XII activity | Standard Deviation 20.4 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H12:00 | 113.6 Percentage of Factor XII activity | Standard Deviation 27.4 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H04:00 | 117.0 Percentage of Factor XII activity | Standard Deviation 29.1 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H07:00 | 116.8 Percentage of Factor XII activity | Standard Deviation 29.2 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 5 H96:00 | 121.6 Percentage of Factor XII activity | Standard Deviation 29.3 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 10 (discharge visit) | 114.3 Percentage of Factor XII activity | Standard Deviation 27.5 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H16:00 | 112.8 Percentage of Factor XII activity | Standard Deviation 29 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H02:00 | 113.5 Percentage of Factor XII activity | Standard Deviation 26.7 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H06:30 | 116.3 Percentage of Factor XII activity | Standard Deviation 25.2 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H00:00 (baseline) | 111.0 Percentage of Factor XII activity | Standard Deviation 28.3 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 4 H72:00 | 120.4 Percentage of Factor XII activity | Standard Deviation 29.6 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 2 H24:00 | 116.5 Percentage of Factor XII activity | Standard Deviation 27 |
| Placebo | Measurement of the Effect of Ir-CPI on Factor XII Activity | Day 1 H01:30 | 111.4 Percentage of Factor XII activity | Standard Deviation 25.6 |
Secondary
Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT)
The activated partial thromboplastin time (aPTT) is used as a pharmacodynamic marker. No data were available for the Ir-CPI 1.5 mg/kg group because the results were not usable due to plasma preparation and method repeatability problems. An aPTT ratio was calculated by dividing the aPTT value (in sec) of the specific time-point (aPTTt) by the baseline aPTT value (in sec) (aPTTbaseline) of the same participant (aPTT ratio = aPTTt/aPTTbaseline). The baseline time-point (Day 1 H00:00) was considered as having an aPTT ratio of 1. Concerning the row titles, for example, Day 1 H02:00 corresponds to aPTT ratio results obtained on Day 1, 2 hours after the start of the infusion.
Time frame: Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days)
Population: This analysis was performed on the Pharmacodyamic Set (PDS): all of the included participants who completed the study without any protocol deviation affecting PD evaluation and with at least one available post-baseline PD data point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:00 (baseline) | 1.000 aPTT ratio | Standard Deviation 0 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H04:00 | 2.148 aPTT ratio | Standard Deviation 0.141 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H12:00 | 1.540 aPTT ratio | Standard Deviation 0.12 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H10:00 | 1.638 aPTT ratio | Standard Deviation 0.113 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H08:00 | 1.775 aPTT ratio | Standard Deviation 0.097 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:00 | 2.207 aPTT ratio | Standard Deviation 0.119 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H16:00 | 1.428 aPTT ratio | Standard Deviation 0.115 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 10 (discharge visit) | 0.972 aPTT ratio | Standard Deviation 0.078 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 4 H72:00 | 1.025 aPTT ratio | Standard Deviation 0.107 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:30 | 2.045 aPTT ratio | Standard Deviation 0.109 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:30 | 1.535 aPTT ratio | Standard Deviation 0.093 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H01:00 | 1.707 aPTT ratio | Standard Deviation 0.073 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 5 H96:00 | 0.990 aPTT ratio | Standard Deviation 0.094 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H07:00 | 1.917 aPTT ratio | Standard Deviation 0.105 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H02:00 | 1.915 aPTT ratio | Standard Deviation 0.079 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H01:30 | 1.827 aPTT ratio | Standard Deviation 0.091 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 3 H48:00 | 1.125 aPTT ratio | Standard Deviation 0.109 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H07:30 | 1.842 aPTT ratio | Standard Deviation 0.093 |
| Ir-CPI - Dose 1 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 2 H24:00 | 1.312 aPTT ratio | Standard Deviation 0.151 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H07:30 | 2.103 aPTT ratio | Standard Deviation 0.131 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 2 H24:00 | 1.585 aPTT ratio | Standard Deviation 0.107 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H08:00 | 2.098 aPTT ratio | Standard Deviation 0.161 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 5 H96:00 | 1.037 aPTT ratio | Standard Deviation 0.088 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H10:00 | 1.942 aPTT ratio | Standard Deviation 0.154 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H16:00 | 1.705 aPTT ratio | Standard Deviation 0.102 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H12:00 | 1.842 aPTT ratio | Standard Deviation 0.119 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H01:30 | 2.225 aPTT ratio | Standard Deviation 0.122 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H02:00 | 2.367 aPTT ratio | Standard Deviation 0.143 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:30 | 1.825 aPTT ratio | Standard Deviation 0.133 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H04:00 | 2.583 aPTT ratio | Standard Deviation 0.218 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:00 (baseline) | 1.000 aPTT ratio | Standard Deviation 0 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 4 H72:00 | 1.113 aPTT ratio | Standard Deviation 0.118 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:00 | 2.652 aPTT ratio | Standard Deviation 0.26 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:30 | 2.442 aPTT ratio | Standard Deviation 0.222 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 3 H48:00 | 1.277 aPTT ratio | Standard Deviation 0.106 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H07:00 | 2.240 aPTT ratio | Standard Deviation 0.154 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H01:00 | 2.085 aPTT ratio | Standard Deviation 0.131 |
| Ir-CPI - Dose 2 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 10 (discharge visit) | 0.967 aPTT ratio | Standard Deviation 0.072 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 4 H72:00 | 1.172 aPTT ratio | Standard Deviation 0.053 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:00 (baseline) | 1.000 aPTT ratio | Standard Deviation 0 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:30 | 2.218 aPTT ratio | Standard Deviation 0.358 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H01:00 | 2.397 aPTT ratio | Standard Deviation 0.296 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H01:30 | 2.533 aPTT ratio | Standard Deviation 0.185 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H02:00 | 2.692 aPTT ratio | Standard Deviation 0.214 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H04:00 | 2.822 aPTT ratio | Standard Deviation 0.096 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:00 | 3.050 aPTT ratio | Standard Deviation 0.189 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:30 | 2.798 aPTT ratio | Standard Deviation 0.184 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H07:00 | 2.558 aPTT ratio | Standard Deviation 0.113 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H07:30 | 2.402 aPTT ratio | Standard Deviation 0.206 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H08:00 | 1.098 aPTT ratio | Standard Deviation 0.161 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H10:00 | 2.230 aPTT ratio | Standard Deviation 0.108 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H12:00 | 2.137 aPTT ratio | Standard Deviation 0.116 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H16:00 | 1.947 aPTT ratio | Standard Deviation 0.096 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 2 H24:00 | 1.718 aPTT ratio | Standard Deviation 0.116 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 3 H48:00 | 1.390 aPTT ratio | Standard Deviation 0.064 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 5 H96:00 | 1.062 aPTT ratio | Standard Deviation 0.049 |
| Ir-CPI - Dose 3 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 10 (discharge visit) | 0.978 aPTT ratio | Standard Deviation 0.067 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H07:30 | 0.950 aPTT ratio | Standard Deviation 0.121 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:30 | 0.982 aPTT ratio | Standard Deviation 0.115 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 2 H24:00 | 0.965 aPTT ratio | Standard Deviation 0.103 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H07:00 | 0.972 aPTT ratio | Standard Deviation 0.101 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:30 | 0.982 aPTT ratio | Standard Deviation 0.109 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H00:00 (baseline) | 1.000 aPTT ratio | Standard Deviation 0 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 3 H48:00 | 0.945 aPTT ratio | Standard Deviation 0.117 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H06:00 | 0.973 aPTT ratio | Standard Deviation 0.116 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H04:00 | 0.970 aPTT ratio | Standard Deviation 0.094 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H02:00 | 0.972 aPTT ratio | Standard Deviation 0.094 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 4 H72:00 | 0.988 aPTT ratio | Standard Deviation 0.133 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H01:30 | 0.982 aPTT ratio | Standard Deviation 0.102 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H01:00 | 0.962 aPTT ratio | Standard Deviation 0.097 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 10 (discharge visit) | 0.985 aPTT ratio | Standard Deviation 0.128 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H12:00 | 0.952 aPTT ratio | Standard Deviation 0.106 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H10:00 | 0.922 aPTT ratio | Standard Deviation 0.117 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 5 H96:00 | 0.942 aPTT ratio | Standard Deviation 0.098 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H16:00 | 0.987 aPTT ratio | Standard Deviation 0.075 |
| Ir-CPI - Dose 4 | Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT) | Day 1 H08:00 | 0.945 aPTT ratio | Standard Deviation 0.102 |
Secondary
Measurement of the Maximum Plasma Concentration (Cmax) of Ir-CPI
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only)
Population: Pharmacokinetic set (PKS): all of the included participants who were administered a complete infusion of study drug without major protocol deviation affecting PK evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ir-CPI - Dose 1 | Measurement of the Maximum Plasma Concentration (Cmax) of Ir-CPI | 958.8 ng/mL | Standard Deviation 98.6 |
| Ir-CPI - Dose 2 | Measurement of the Maximum Plasma Concentration (Cmax) of Ir-CPI | 2013.2 ng/mL | Standard Deviation 228.2 |
| Ir-CPI - Dose 3 | Measurement of the Maximum Plasma Concentration (Cmax) of Ir-CPI | 3752.5 ng/mL | Standard Deviation 422.3 |
| Ir-CPI - Dose 4 | Measurement of the Maximum Plasma Concentration (Cmax) of Ir-CPI | 6288.3 ng/mL | Standard Deviation 757 |
Secondary
Measurement of the Time to Reach Maximum Plasma Concentration (Tmax) of Ir-CPI
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only)
Population: Pharmacokinetic set (PKS): all of the included participants who were administered a complete infusion of study drug without major protocol deviation affecting PK evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ir-CPI - Dose 1 | Measurement of the Time to Reach Maximum Plasma Concentration (Tmax) of Ir-CPI | 6 hours | Standard Deviation 0 |
| Ir-CPI - Dose 2 | Measurement of the Time to Reach Maximum Plasma Concentration (Tmax) of Ir-CPI | 6 hours | Standard Deviation 0 |
| Ir-CPI - Dose 3 | Measurement of the Time to Reach Maximum Plasma Concentration (Tmax) of Ir-CPI | 6 hours | Standard Deviation 0 |
| Ir-CPI - Dose 4 | Measurement of the Time to Reach Maximum Plasma Concentration (Tmax) of Ir-CPI | 6 hours | Standard Deviation 0 |