Healthy Subjects
Conditions
Keywords
Phase 1, healthy male subjects, safety and tolerability, pharmacodynamic, pharmacokinetic
Brief summary
A study to investigate the safety, tolerability and pharmacodynamics of MEDI8111 after single ascending doses in healthy male.
Detailed description
A phase I, single-blind, randomised, placebo-controlled, single centre study to investigate the safety, tolerability and pharmacodynamics of intravenous MEDI8111 after single ascending doses in healthy male subjects.
Interventions
DRUGMEDI8111
MEDI8111 lyophilisate for solution for infusion
OTHERPlacebo
Placebo for MEDI8111 saline solution for infusion
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Provision of signed and dated, written informed consent prior to any study specific procedures, Healthy male subjects aged 18-40 years with suitable veins for cannulation or repeated venepuncture, Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weight at least 50 kg an no more than 100 kg inclusive, Male subjects should be willing to avoid fathering a child by either true abstinence or the use of two effective means of contraception from the day of dosing until 3 months after dosing with the IP. They should also be willing to use barrier methods from the day of dosing until 3 months after dosing.
Exclusion criteria
* Prothrombotic mutation such as factor V Leiden, or deficiencies of protein C, protein S, prothrombin, antithrombin or APC, Antibodies to coagulation FII, History or family history of venous or arterial thromboembolic event, and/or myocardial infarction before age of 50 years, ETP level at baseline \>2000nM/min, FII level (by clot) at screening and/or at baseline outside 50-250% of the normal range
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | From screening and up to the lab follow-up visit (Day 29) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Endogenous Thrombin Potential (ETP) | Predose and Days 1-5 | For the baseline variables and adverse events the two placebo arms (placebo dose 1 and placebo dose 2) are recorded as one. For the secondary outcome measures the two placebo arms are recorded separately. |
| Change From Baseline Factor II Concentrations by ECL Assay | Predose and 1-8 hours | — |
| Change From Baseline Factor II Concentrations by Clot Assay | Predose and 1-8 hours | — |
| Change From Baseline D-dimer Concentration | predose and 1-8 hours | — |
Countries
United Kingdom
Participant flow
Recruitment details
Male healthy volunteers recruited by advertisement during the period October 2013 - October 2014
Pre-assignment details
The study was prematurely terminated after 2 cohorts as dose escalation stopping criteria (PD thresholds) were reached and it was judged to be of limited value to expose more healthy subjects. Cohort 1: 2 placebo + 4 MEDI8111 dose 1. Cohort 2: 2 placebo + 4 MEDI8111 dose 2.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (Saline solution for infusion) | 4 |
| MEDI8111 Dose 1 MEDI8111 dose 1 (Lyophilisate for solution for infusion, 30 mg) | 4 |
| MEDI8111 Dose 2 MEDI8111 dose 2 (Lyophilisate for solution for infusion, 30 mg) | 4 |
| Total | 12 |
Baseline characteristics
| Characteristic | Placebo | MEDI8111 Dose 1 | MEDI8111 Dose 2 | Total |
|---|---|---|---|---|
| Age, Continuous | 25 years STANDARD_DEVIATION 9 | 30 years STANDARD_DEVIATION 6 | 30 years STANDARD_DEVIATION 6 | 29 years STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 4 | 3 / 4 | 2 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination
Time frame: From screening and up to the lab follow-up visit (Day 29)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Skin and subcutaneous tissue disorders | 1 Participants |
| Placebo | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Subjects with any AE | 2 Participants |
| Placebo | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Investigations | 0 Participants |
| Placebo | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| Placebo | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Gastrointestinal disorders | 1 Participants |
| Placebo | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Musculoskeletal and connective tissue disorders | 0 Participants |
| Placebo | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Infections and infestations | 0 Participants |
| Placebo | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Nervous system disorder | 0 Participants |
| MEDI8111 Dose 1 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Gastrointestinal disorders | 1 Participants |
| MEDI8111 Dose 1 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Nervous system disorder | 1 Participants |
| MEDI8111 Dose 1 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| MEDI8111 Dose 1 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Subjects with any AE | 3 Participants |
| MEDI8111 Dose 1 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Skin and subcutaneous tissue disorders | 0 Participants |
| MEDI8111 Dose 1 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Infections and infestations | 1 Participants |
| MEDI8111 Dose 1 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Investigations | 1 Participants |
| MEDI8111 Dose 1 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Musculoskeletal and connective tissue disorders | 1 Participants |
| MEDI8111 Dose 2 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Skin and subcutaneous tissue disorders | 0 Participants |
| MEDI8111 Dose 2 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Subjects with any AE | 2 Participants |
| MEDI8111 Dose 2 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Gastrointestinal disorders | 1 Participants |
| MEDI8111 Dose 2 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Infections and infestations | 1 Participants |
| MEDI8111 Dose 2 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Investigations | 0 Participants |
| MEDI8111 Dose 2 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Musculoskeletal and connective tissue disorders | 0 Participants |
| MEDI8111 Dose 2 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Respiratory, thoracic and mediastinal disorders | 1 Participants |
| MEDI8111 Dose 2 | Description of the Safety Profile in Terms of Adverse Events (AE),Vital Signs, ECG, Lab Variables, Immunogenicity and Physical Examination | Nervous system disorder | 0 Participants |
Secondary
Change From Baseline D-dimer Concentration
Time frame: predose and 1-8 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline D-dimer Concentration | 0.98 h | -0.0169 mg/L | Standard Deviation 0.0144 |
| Placebo | Change From Baseline D-dimer Concentration | 1.03 h | 0.0432 mg/L | Standard Deviation 0.0564 |
| Placebo | Change From Baseline D-dimer Concentration | 1.25 h | 0.0232 mg/L | Standard Deviation 0.113 |
| Placebo | Change From Baseline D-dimer Concentration | 1.5 h | -0.00185 mg/L | Standard Deviation 0.0214 |
| Placebo | Change From Baseline D-dimer Concentration | 2 h | 0.0682 mg/L | Standard Deviation 0.135 |
| Placebo | Change From Baseline D-dimer Concentration | 3 h | 0.0732 mg/L | Standard Deviation 0.0846 |
| Placebo | Change From Baseline D-dimer Concentration | 4 h | NA mg/L | — |
| Placebo | Change From Baseline D-dimer Concentration | 8 h | 0.588 mg/L | Standard Deviation 0.799 |
| MEDI8111 Dose 1 | Change From Baseline D-dimer Concentration | 3 h | 0.00325 mg/L | Standard Deviation 0.0237 |
| MEDI8111 Dose 1 | Change From Baseline D-dimer Concentration | 2 h | 0.0382 mg/L | Standard Deviation 0.0813 |
| MEDI8111 Dose 1 | Change From Baseline D-dimer Concentration | 1.03 h | 0.0383 mg/L | Standard Deviation 0.109 |
| MEDI8111 Dose 1 | Change From Baseline D-dimer Concentration | 8 h | 0.0858 mg/L | Standard Deviation 0.0914 |
| MEDI8111 Dose 1 | Change From Baseline D-dimer Concentration | 4 h | NA mg/L | — |
| MEDI8111 Dose 1 | Change From Baseline D-dimer Concentration | 1.5 h | 0.408 mg/L | Standard Deviation 0.795 |
| MEDI8111 Dose 1 | Change From Baseline D-dimer Concentration | 1.25 h | 0.000750 mg/L | Standard Deviation 0.0336 |
| MEDI8111 Dose 1 | Change From Baseline D-dimer Concentration | 0.98 h | 0.0408 mg/L | Standard Deviation 0.103 |
| MEDI8111 Dose 2 | Change From Baseline D-dimer Concentration | 4 h | 0.0933 mg/L | Standard Deviation 0.081 |
| MEDI8111 Dose 2 | Change From Baseline D-dimer Concentration | 1.25 h | 0.0333 mg/L | Standard Deviation 0.0306 |
| MEDI8111 Dose 2 | Change From Baseline D-dimer Concentration | 1.5 h | NA mg/L | — |
| MEDI8111 Dose 2 | Change From Baseline D-dimer Concentration | 2 h | 0.0610 mg/L | Standard Deviation 0.076 |
| MEDI8111 Dose 2 | Change From Baseline D-dimer Concentration | 3 h | NA mg/L | — |
| MEDI8111 Dose 2 | Change From Baseline D-dimer Concentration | 8 h | 0.0633 mg/L | Standard Deviation 0.063 |
| MEDI8111 Dose 2 | Change From Baseline D-dimer Concentration | 0.98 h | NA mg/L | — |
| MEDI8111 Dose 2 | Change From Baseline D-dimer Concentration | 1.03 h | 0.0108 mg/L | Standard Deviation 0.019 |
| Placebo Dose 2 | Change From Baseline D-dimer Concentration | 1.25 h | 0.0170 mg/L | Standard Deviation 0.0566 |
| Placebo Dose 2 | Change From Baseline D-dimer Concentration | 1.5 h | NA mg/L | — |
| Placebo Dose 2 | Change From Baseline D-dimer Concentration | 1.03 h | 0.0270 mg/L | Standard Deviation 0.0141 |
| Placebo Dose 2 | Change From Baseline D-dimer Concentration | 0.98 h | NA mg/L | — |
| Placebo Dose 2 | Change From Baseline D-dimer Concentration | 2 h | 0.0170 mg/L | Standard Deviation 0.0424 |
| Placebo Dose 2 | Change From Baseline D-dimer Concentration | 8 h | 0.0470 mg/L | Standard Deviation 0.0849 |
| Placebo Dose 2 | Change From Baseline D-dimer Concentration | 4 h | 0.207 mg/L | Standard Deviation 0.0849 |
| Placebo Dose 2 | Change From Baseline D-dimer Concentration | 3 h | NA mg/L | — |
Secondary
Change From Baseline Endogenous Thrombin Potential (ETP)
For the baseline variables and adverse events the two placebo arms (placebo dose 1 and placebo dose 2) are recorded as one. For the secondary outcome measures the two placebo arms are recorded separately.
Time frame: Predose and Days 1-5
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 48 h | 29.0 nM*min | Standard Deviation 222 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 96 h | -95.0 nM*min | Standard Deviation 209 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 2 h | 32.5 nM*min | Standard Deviation 148 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.25 h | 67.0 nM*min | Standard Deviation 356 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.03 h | 30.5 nM*min | Standard Deviation 138 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 3 h | 57.0 nM*min | Standard Deviation 238 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 36 h | -59.0 nM*min | Standard Deviation 134 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | Follow up | -12.5 nM*min | Standard Deviation 13.4 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 0.98 h | 16 nM*min | Standard Deviation 143 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 4 h | -88.0 nM*min | Standard Deviation 226 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 12 h | 82.5 nM*min | Standard Deviation 70 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.5 h | 166 nM*min | Standard Deviation 75 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 72 h | 183 nM*min | Standard Deviation 222 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 8 h | 157 nM*min | Standard Deviation 161 |
| Placebo | Change From Baseline Endogenous Thrombin Potential (ETP) | 24 h | -29.0 nM*min | Standard Deviation 279 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 8 h | 141 nM*min | Standard Deviation 288 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 12 h | 366 nM*min | Standard Deviation 396 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 36 h | 329 nM*min | Standard Deviation 496 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 24 h | 115 nM*min | Standard Deviation 336 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.25 h | 135 nM*min | Standard Deviation 345 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 96 h | -1.00 nM*min | Standard Deviation 483 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.5 h | -17.3 nM*min | Standard Deviation 120 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | Follow up | -34.5 nM*min | Standard Deviation 206 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 2 h | 178 nM*min | Standard Deviation 336 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 3 h | 188 nM*min | Standard Deviation 385 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.03 h | 145 nM*min | Standard Deviation 263 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 72 h | 71.5 nM*min | Standard Deviation 274 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 4 h | 72.8 nM*min | Standard Deviation 545 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 0.98 h | 131 nM*min | Standard Deviation 219 |
| MEDI8111 Dose 1 | Change From Baseline Endogenous Thrombin Potential (ETP) | 48 h | 172 nM*min | Standard Deviation 264 |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 8 h | 83.0 nM*min | Standard Deviation 216 |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 0.98 h | NA nM*min | — |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.03 h | 39.8 nM*min | Standard Deviation 72.1 |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.25 h | 211 nM*min | Standard Deviation 179 |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.5 h | NA nM*min | — |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 2 h | 147 nM*min | Standard Deviation 167 |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 3 h | NA nM*min | — |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 4 h | 157 nM*min | Standard Deviation 277 |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 12 h | NA nM*min | — |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 24 h | 86.0 nM*min | Standard Deviation 120 |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 36 h | NA nM*min | — |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 48 h | 206 nM*min | Standard Deviation 261 |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 72 h | 139 nM*min | Standard Deviation 194 |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 96 h | 64.8 nM*min | Standard Deviation 223 |
| MEDI8111 Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | Follow up | NA nM*min | — |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 2 h | -79.5 nM*min | Standard Deviation 95.5 |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.03 h | -35.0 nM*min | Standard Deviation 214 |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 48 h | 91.0 nM*min | Standard Deviation 26.9 |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 4 h | 4.50 nM*min | Standard Deviation 48.8 |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 3 h | NA nM*min | — |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 0.98 h | NA nM*min | — |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 72 h | 73.5 nM*min | Standard Deviation 9.19 |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.5 h | NA nM*min | — |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 1.25 h | 27.0 nM*min | Standard Deviation 80.6 |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | Follow up | NA nM*min | — |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 24 h | 70.5 nM*min | Standard Deviation 14.8 |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 12 h | NA nM*min | — |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 96 h | 46.0 nM*min | Standard Deviation 8.49 |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 36 h | NA nM*min | — |
| Placebo Dose 2 | Change From Baseline Endogenous Thrombin Potential (ETP) | 8 h | 6.50 nM*min | Standard Deviation 33.2 |
Secondary
Change From Baseline Factor II Concentrations by Clot Assay
Time frame: Predose and 1-8 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Factor II Concentrations by Clot Assay | 0.33 h | 7.65 % (concentration) | Standard Deviation 26.4 |
| Placebo | Change From Baseline Factor II Concentrations by Clot Assay | 0.67 h | 3.15 % (concentration) | Standard Deviation 17.2 |
| Placebo | Change From Baseline Factor II Concentrations by Clot Assay | 0.98 h | -9.35 % (concentration) | Standard Deviation 12.2 |
| Placebo | Change From Baseline Factor II Concentrations by Clot Assay | 1 h | -14.4 % (concentration) | Standard Deviation 13.6 |
| Placebo | Change From Baseline Factor II Concentrations by Clot Assay | 1.25 | -6.85 % (concentration) | Standard Deviation 18.6 |
| Placebo | Change From Baseline Factor II Concentrations by Clot Assay | 1.5 h | -10.9 % (concentration) | Standard Deviation 12.9 |
| Placebo | Change From Baseline Factor II Concentrations by Clot Assay | 2 h | -8.85 % (concentration) | Standard Deviation 8.7 |
| Placebo | Change From Baseline Factor II Concentrations by Clot Assay | 3 h | -5.85 % (concentration) | Standard Deviation 12.9 |
| Placebo | Change From Baseline Factor II Concentrations by Clot Assay | 4 h | 0.150 % (concentration) | Standard Deviation 15.8 |
| Placebo | Change From Baseline Factor II Concentrations by Clot Assay | 8 h | -9.85 % (concentration) | Standard Deviation 10.1 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by Clot Assay | 0.98 h | -2.40 % (concentration) | Standard Deviation 4.25 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by Clot Assay | 4 h | 2.10 % (concentration) | Standard Deviation 4.45 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by Clot Assay | 1 h | -1.15 % (concentration) | Standard Deviation 4.22 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by Clot Assay | 1.25 | -0.400 % (concentration) | Standard Deviation 5.54 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by Clot Assay | 1.5 h | -0.400 % (concentration) | Standard Deviation 8.67 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by Clot Assay | 2 h | 0.350 % (concentration) | Standard Deviation 5.45 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by Clot Assay | 8 h | -1.90 % (concentration) | Standard Deviation 5.78 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by Clot Assay | 3 h | 1.10 % (concentration) | Standard Deviation 9.73 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by Clot Assay | 0.33 h | -1.40 % (concentration) | Standard Deviation 7.67 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by Clot Assay | 0.67 h | 1.35 % (concentration) | Standard Deviation 6.95 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 3 h | NA % (concentration) | — |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 2 h | 10.5 % (concentration) | Standard Deviation 7.84 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 8 h | 11.7 % (concentration) | Standard Deviation 9.12 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 0.33 h | NA % (concentration) | — |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 1 h | 13.7 % (concentration) | Standard Deviation 14.5 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 1.5 h | NA % (concentration) | — |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 4 h | 18.2 % (concentration) | Standard Deviation 9.02 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 0.67 h | NA % (concentration) | — |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 1.25 | 12.2 % (concentration) | Standard Deviation 9.55 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 0.98 h | NA % (concentration) | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 1.25 | 8.30 % (concentration) | Standard Deviation 1.41 |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 3 h | NA % (concentration) | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 1.5 h | NA % (concentration) | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 8 h | 9.30 % (concentration) | Standard Deviation 4.24 |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 2 h | 2.80 % (concentration) | Standard Deviation 4.95 |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 0.67 h | NA % (concentration) | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 0.98 h | NA % (concentration) | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 1 h | 7.30 % (concentration) | Standard Deviation 0 |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 0.33 h | NA % (concentration) | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by Clot Assay | 4 h | 7.30 % (concentration) | Standard Deviation 4.24 |
Secondary
Change From Baseline Factor II Concentrations by ECL Assay
Time frame: Predose and 1-8 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Factor II Concentrations by ECL Assay | 0.98 h | -0.134 umol/L | Standard Deviation 0.0368 |
| Placebo | Change From Baseline Factor II Concentrations by ECL Assay | 0.33 h | -0.0810 umol/L | Standard Deviation 0.041 |
| Placebo | Change From Baseline Factor II Concentrations by ECL Assay | 0.67 h | -0.0480 umol/L | Standard Deviation 0.0113 |
| Placebo | Change From Baseline Factor II Concentrations by ECL Assay | 1 h | -0.131 umol/L | Standard Deviation 0.0156 |
| Placebo | Change From Baseline Factor II Concentrations by ECL Assay | 1.25 h | -0.143 umol/L | Standard Deviation 0.00354 |
| Placebo | Change From Baseline Factor II Concentrations by ECL Assay | 1.5 h | -0.132 umol/L | Standard Deviation 0.121 |
| Placebo | Change From Baseline Factor II Concentrations by ECL Assay | 2 h | -0.0655 umol/L | Standard Deviation 0.0629 |
| Placebo | Change From Baseline Factor II Concentrations by ECL Assay | 3 h | -0.0675 umol/L | Standard Deviation 0.248 |
| Placebo | Change From Baseline Factor II Concentrations by ECL Assay | 4 h | -0.127 umol/L | Standard Deviation 0.279 |
| Placebo | Change From Baseline Factor II Concentrations by ECL Assay | 8 h | 0.00650 umol/L | Standard Deviation 0.122 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by ECL Assay | 0.98 h | 0.00450 umol/L | Standard Deviation 0.0896 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by ECL Assay | 4 h | 0.123 umol/L | Standard Deviation 0.0663 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by ECL Assay | 1 h | -0.0305 umol/L | Standard Deviation 0.0435 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by ECL Assay | 1.25 h | -0.0920 umol/L | Standard Deviation 0.0881 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by ECL Assay | 1.5 h | -0.124 umol/L | Standard Deviation 0.148 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by ECL Assay | 2 h | 0.00450 umol/L | Standard Deviation 0.188 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by ECL Assay | 8 h | 0.0633 umol/L | Standard Deviation 0.0801 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by ECL Assay | 3 h | 0.0608 umol/L | Standard Deviation 0.12 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by ECL Assay | 0.33 h | -0.0188 umol/L | Standard Deviation 0.0661 |
| MEDI8111 Dose 1 | Change From Baseline Factor II Concentrations by ECL Assay | 0.67 h | 0.0275 umol/L | Standard Deviation 0.0377 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 3 h | NA umol/L | — |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 8 h | 0.0835 umol/L | Standard Deviation 0.0731 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 2 h | 0.111 umol/L | Standard Deviation 0.129 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 1.5 h | NA umol/L | — |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 1 h | 0.166 umol/L | Standard Deviation 0.0632 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 0.98 h | NA umol/L | — |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 4 h | 0.141 umol/L | Standard Deviation 0.155 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 0.33 h | NA umol/L | — |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 1.25 h | 0.116 umol/L | Standard Deviation 0.113 |
| MEDI8111 Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 0.67 h | NA umol/L | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 1.25 h | 0.0600 umol/L | Standard Deviation 0.0424 |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 0.33 h | NA umol/L | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 1.5 h | NA umol/L | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 8 h | -0.00900 umol/L | Standard Deviation 0.041 |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 2 h | 0.0800 umol/L | Standard Deviation 0.0849 |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 0.98 h | NA umol/L | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 3 h | NA umol/L | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 0.67 h | NA umol/L | — |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 1 h | 0.0650 umol/L | Standard Deviation 0.0212 |
| Placebo Dose 2 | Change From Baseline Factor II Concentrations by ECL Assay | 4 h | 0.0450 umol/L | Standard Deviation 0.0495 |