Healthy Male Participants
Conditions
Brief summary
This is a Phase I, open-label, non-randomized, parallel-group, single-dose study in healthy adult male participants. The aim is to investigate the relative bioavailability (rBA) of NXT007 among subcutaneous (SC) injection sites (abdomen, upper arm, and thigh) and the absolute bioavailability (aBA) of SC NXT007 administration. In addition, the pharmacodynamic, safety, tolerability, and immunogenicity of a single dose of NXT007 following SC or intravenous (IV) administration are assessed.
Interventions
DRUGNXT007
In all groups, the NXT007 single dose administration will occur in the morning of Day 1 under fasted conditions. Study treatment will occur via the route of administration and at the site of injection specified for each group.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy as determined by medical evaluation that includes medical history, physical examination, vital signs, laboratory tests, and 12-lead ECG * Body mass index (BMI) within the range of 18.5 to 30.0 kg/m\^2 * Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm
Exclusion criteria
* History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, immunological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data * History of allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies; or known hypersensitivity to any constituent of the product * Clinically relevant medical history and/or family history or signs of thromboembolic disease such as deep vein thrombosis * FVIII activity ≥120 International Units per decilitre (IU/dL) at screening * Clinically significant abnormality on electrocardiogram (ECG) at screening such as QTcF after 10-minute supine rest \>450 milliseconds (ms); marked resting bradycardia (mean heart rate \<40 beats per minute \[bpm\]); marked resting tachycardia (mean heart rate \>100 bpm); or any other clinically significant ECG abnormality * Supine systolic blood pressure at screening ≥140 millimetres of mercury (mm Hg) or \<90 mm Hg or supine diastolic blood pressure at screening ≥90 mm Hg or \<40 mm Hg * Clinically significant abnormality on protein C activity (chromogenic assay), activated protein C resistance test, protein S free antigen, and/or antithrombin III activity levels * Poor peripheral venous access * Any other reason that, in the judgment of the investigator, would render the participants unsuitable for study participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of NXT007 | At prespecified timepoints from Day 1 until Day 253 |
| Maximum Observed Plasma Concentration (Cmax) of NXT007 | At prespecified timepoints from Day 1 until Day 253 |
Secondary
| Measure | Time frame |
|---|---|
| Time to Maximum Observed Plasma Concentration (tmax) of NXT007 | At prespecified timepoints from Day 1 until Day 253 |
| Apparent Terminal Half-Life (t1/2) of NXT007 | At prespecified timepoints from Day 1 until Day 253 |
| Apparent Clearance (CL/F) of NXT007 SC Administration | At prespecified timepoints from Day 1 until Day 253 |
| Total Body Clearance (CL) of NXT007 IV Administration | At prespecified timepoints from Day 1 until Day 253 |
| Incidence and Severity of Adverse Events | From the single dose of study treatment (Day 1) until study completion (Day 253) |
| Number of Participants with Abnormal Laboratory Values in Clinical Chemistry Parameters | From the single dose of study treatment (Day 1) until study completion (Day 253) |
| Number of Participants with Abnormal Laboratory Values in Hematology Parameters | From the single dose of study treatment (Day 1) until study completion (Day 253) |
| Change from Baseline in Pulse Rate at Specified Timepoints | Baseline, Days 1, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225, and 253 |
| Volume of Distribution at Steady State of NXT007 IV Administration | At prespecified timepoints from Day 1 until Day 253 |
| Change from Baseline in Systolic Blood Pressure at Specified Timepoints | Baseline, Days 1, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225, and 253 |
| Change from Baseline in Diastolic Blood Pressure at Specified Timepoints | Baseline, Days 1, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225, and 253 |
| Change from Baseline in Heart Rate at Specified Timepoints, as Measured by Electrocardiogram | Baseline, Days 1, 2, 8, 22, 43, 71, 141, and 253 |
| Change from Baseline in RR, PR, QRS, QT, and QTcF Intervals at Specified Timepoints, as Measured by Electrocardiogram | Baseline, Days 1, 2, 8, 22, 43, 71, 141, and 253 |
| Change from Baseline in Activated Partial Thromboplastin Time (aPTT) at Specified Timepoints | Baseline, Days 1, 2, 8, 15, 18, 20, 22, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225, and 253 |
| Change from Baseline in the Maximum Concentration of Thrombin Generated at Specified Timepoints | Baseline, Days 1, 18, 20, and 22 |
| Prevalence of Anti-Drug Antibodies (ADAs) to NXT007 at Baseline and Incidence of ADAs to NXT007 During the Study | From Baseline until Day 253 |
| Change from Baseline in Tympanic Temperature at Specified Timepoints | Baseline, Days 1, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225, and 253 |
| Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUC0-last) of NXT007 | At prespecified timepoints from Day 1 until Day 253 |
Countries
New Zealand
Outcome results
None listed