This is a single-centre, single ascending dose (SAD) pilot study designed to evaluate the safety, tolerability, including local tolerability, and pharmacokinetics (PK) of NEX-20A (lenalidomide) after the administration of a single subcutaneous prolonged-release injection to healthy male volunteers
NEX-20A will be administered in sequential cohorts, 2 standard cohorts and an optional third cohort, each comprising 3 subjects. Subjects will be dosed in a sentinel fashion, and all available safety and tolerability data up until and including 10 days for the sentinel subjects must have been evaluated by the iSRC before dosing the remaining 2 subjects in each cohort.Once safety, tolerability and PK data of the last subject in each cohort has been collected, and interim data analysis has been conducted, there must be at least 1 week between dose escalations.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Subcutaneous prolonged-release injection
CTC Clinical Research Consultants AB
Uppsala, Sweden
Number of subjects with a clinical significant change from baseline in the systolic blood pressure at 36 days
Measured in mmHg after 10 minutes supine rest. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the diastolic blood pressure at 36 days
Measured in mmHg after 10 minutes supine rest. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the ECG parameter PQ/PR at 36 days
Measured in ms in supine position after 10 minutes of rest using an ECG machine. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the ECG parameter QRS at 36 days
Measured in ms in supine position after 10 minutes of rest using an ECG machine. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the ECG parameter QT at 36 days
Measured in ms in supine position after 10 minutes of rest using an ECG machine. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the ECG parameter QTcF at 36 days
Measured in ms in supine position after 10 minutes of rest using an ECG machine. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the haematology blood parameters measurements at 36 days
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Blood samples for the analysis of haematology will be collected through venepuncture or an indwelling venous catheter. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the clinical chemistry blood laboratory measurements at 36 days
Blood samples for the analysis of clinical chemistry parameters will be collected through venepuncture or an indwelling venous catheter. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the coagulation parameters blood laboratory measurements at 36 days
Blood samples for the analysis of clinical coagulation parameters will be collected through venpuncture or an indwelling venous catheter. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of the head at 36 days
Physical examination including assessment of the head. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of eyes at 36 days
Physical examination including assessment of the eyes. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of the ears at 36 days
Physical examination including assessment of the ears.Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of the nose at 36 days
Physical examination including assessment of the nose.Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of the throat at 36 days
Physical examination including assessment of the throat. .Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of the skin at 36 days
Physical examination including assessment of the skin. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of the thyroid at 36 days
Physical examination including assessment of the thyroid. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of neurological status at 36 days
Physical examination including neurological status. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of the lungs at 36 days
Physical examination of the lungs including percussion, inspection, palpation, and auscultation.Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the cardiovascular status of at 36 days
Physical examination including inspection, palpation, and auscultation of the heart. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of the abdomen at 36 days
Physical examination including assessments of the abdomen (liver and spleen). Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of lymph nodes at 36 days
Physical examination including assessments of the lymph nodes. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in the physical examination of extremitets at 36 days
Physical examination including assessments of the extremitets. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with treatment-related adverse events a assessed by frequency
Number of events.Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with treatment-related adverse events a assessed by seriousness
Seriousness of adverse events.Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with treatment-related adverse events a assessed by intensity
Intensity of adverse events.Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in local tolerability i.e skin reactions assessed by visual inspection.
Visual inspection. Descriptive individual data.
Time frame: From first dose until day 36
Number of subjects with a clinical significant change from baseline in local tolerability i.e skin reactions assessed by photography.
Photography of injection site. Descriptive individual data.
Time frame: From first dose until day 36
Maximum observed plasma concentration (Cmax)
Measurement of lenalidomid
Time frame: pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 12 hours post-dose on Day 1, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours, 408 hours, 504 hours, 576 hours, 672 hours, 744 hours, 840 hours
Time of occurrence of Cmax (Tmax)
Measurement of lenalidomid
Time frame: pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 12 hours post-dose on Day 1, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours, 408 hours, 504 hours, 576 hours, 672 hours, 744 hours, 840 hours
Area under the plasma concentration vs. time curve (AUC) from time 0 to 8 hours
Measurement of lenalidomid
Time frame: pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 12 hours post-dose on Day 1, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours, 408 hours, 504 hours, 576 hours, 672 hours, 744 hours, 840 hours
AUC from time 0 to 12 hours
Measurement of lenalidomid
Time frame: pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 12 hours post-dose on Day 1, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours, 408 hours, 504 hours, 576 hours, 672 hours, 744 hours, 840 hours
AUC from time 0 to 7 days
Measurement of lenalidomid
Time frame: pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 12 hours post-dose on Day 1, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours, 408 hours, 504 hours, 576 hours, 672 hours, 744 hours, 840 hours
AUC from time 0 to infinity
Measurement of lenalidomid
Time frame: pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 12 hours post-dose on Day 1, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours, 408 hours, 504 hours, 576 hours, 672 hours, 744 hours, 840 hours
Terminal elimination half-life
Measurement of lenalidomid
Time frame: pre-dose and at 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 12 hours post-dose on Day 1, 24 hours, 48 hours, 72 hours, 120 hours, 168 hours, 240 hours, 336 hours, 408 hours, 504 hours, 576 hours, 672 hours, 744 hours, 840 hours