This study will be a phase I, first time in human (FiH), randomized, single-blind, placebo-controlled, SAD study in male patients with T2DM, performed at a single study center. The study will consist of 2 parts, (A and B) up to 60 male patients with T2DM aged 18 to 65 years will be included
Part A will assess the safety and tolerability of SAD of intradermal (ID) injection of AZD8601 (modified VEGF-A RNA) and Part B will evaluate the pharmacodynamic effects of ID injection of AZD8601 in forearm skin. AZD8601 is a VEGF-A modified RNA under development as a novel modality for local production of human VEGF-A protein and is developed for the treatment of diabetic patients with ulcers. Each patient in Part A will be involved in the study for 7 to 8 weeks. Each patient in Part B will be involved in the study for 5 to 6 weeks. Safety and tolerability variables includes Adverse events (AEs), Vital signs (BP, pulse), ECG, Hematology, Clinical chemistry, Urinalysis. The study will include patients with T2DM that are on stable doses of 1 to 2 anti-diabetic medications. The T2DM patients may also be on medications for comorbidities such as hypertension, dyslipidemia, hyperuricemia, thyroid disorders, benign prostate hyperplasia etc. (e.g. diuretics, statins, allopurinol, thyroxin), but must be healthy otherwise.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
44
Six subjects are randomized to receive one treatment of AZD8601 and one treatment of Placebo. Single ascending dose (SAD) with a sequential cohort design and three dose levels of AZD8601 are planned to be investigated. Subjects will receive 0.004 mg per injection of AZD8601/placebo with a total proposed dose of 0.024 mg.
Subjects will receive dose with sufficient vascular endothelial growth factor (VEGF)-A protein production and a good safety profile as determined in Part A and the total dose per patient will not exceed the maximum dose given in Part A.
Subjects are randomized to receive 2 placebo treatments.
Research Site
Berlin, Germany
Safety of AZD8601 by assessing summary of adverse events (Part A)
To evaluate the safety by assessing the adverse event after administration of a single dose of AZD8601 to male subjects with T2DM (Part A).
Time frame: Part A: From screening (Day -28) up to Day 29
Safety of AZD8601 by assessing number of subjects with clinically significant blood pressure (Part A)
To evaluate the safety by assessing the number of subjects with clinically significant blood pressure after administration of single dose of AZD8601 to male subjects with T2DM (Part A).
Time frame: Part A: Day 1 to Day 8
Safety of AZD8601 by assessing number of subjects with Clinically significant pulse (Part A)
To evaluate the safety by assessing the number of subjects with clinically significant pulse after administration of single dose of AZD8601 to male subjects with T2DM (Part A).
Time frame: Part A: Day 1 to Day 8
Safety of AZD8601 by assessing number of subjects with Clinically significant 12-lead electrocardiograms (ECGs) (Part A)
To evaluate the safety by assessing the number of subjects with clinically significant ECGs after administration of single dose of AZD8601 to male subjects with T2DM (Part A).
Time frame: Part A: Day 1 to Day 8
Safety of AZD8601 by assessing number of subjects with clinically significant hematology parameters (Part A)
To evaluate the safety by assessing the number of subjects with clinically significant hematology parameters after administration of single dose of AZD8601 to male subjects with T2DM (Part A).
Time frame: Part A: Day 1 to Day 8
Safety of AZD8601 by assessing number of subjects with clinically significant clinical chemistry laboratory results (Part A)
To evaluate the safety by assessing the number of subjects with clinically significant clinical chemistry laboratory results after administration of single dose of AZD8601 to male subjects with T2DM (Part A).
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Time frame: Part A: Day 1 to Day 8
Safety of AZD8601 by assessing number of subjects with clinically significant urinalysis (Part A)
To evaluate the safety by assessing the number of subjects with clinically significant urinalysis after administration of single dose of AZD8601 to male subjects with T2DM (Part A).
Time frame: Part A: Day 1 to Day 8
Safety of AZD8601 by assessing summary of adverse events (Part B)
To evaluate the safety by assessing the adverse event after administration of a single dose of AZD8601 to male subjects with T2DM (Part B).
Time frame: Part B: From screening up to Day 15
Safety of AZD8601 by assessing number of subjects with clinically significant blood pressure (Part B)
To evaluate the safety by assessing the number of subjects with clinically significant blood pressure after administration of single dose of AZD8601 to male subjects with T2DM (Part B).
Time frame: Part B: Day 1 to Day 2
Safety of AZD8601 by assessing number of subjects with Clinically significant pulse (Part B)
To evaluate the safety by assessing the number of subjects with clinically significant pulse after administration of single dose of AZD8601 to male subjects with T2DM (Part B).
Time frame: Part B: Day 1 to Day 2
Safety of AZD8601 by assessing number of subjects with Clinically significant 12-lead electrocardiograms (ECGs) (Part B)
To evaluate the safety by assessing the number of subjects with clinically significant ECGs after administration of single dose of AZD8601 to male subjects with T2DM (Part B).
Time frame: Part B: Day 1 to Day 2
Safety of AZD8601 by assessing number of subjects with clinically significant hematology parameters (Part B)
To evaluate the safety by assessing the number of subjects with clinically significant hematology parameters after administration of single dose of AZD8601 to male subjects with T2DM (Part B).
Time frame: Part B: Day 1 to Day 2
Safety of AZD8601 by assessing number of subjects with clinically significant clinical chemistry laboratory results (Part B)
To evaluate the safety by assessing the number of subjects with clinically significant clinical chemistry laboratory results after administration of single dose of AZD8601 to male subjects with T2DM (Part B).
Time frame: Part B: Day 1 to Day 2
Safety of AZD8601 by assessing number of subjects with clinically significant urinalysis (Part B)
To evaluate the safety by assessing the number of subjects with clinically significant urinalysis after administration of single dose of AZD8601 to male subjects with T2DM (Part B).
Time frame: Part B: Day 1 to Day 2