A Phase I, Randomized, Single-Blind, Placebo Controlled Study to Assess the Safety, Tolerability and Pharmacodynamics Of AZD8601 After Single Dose Administration to Male Patients With Type II Diabetes Mellitus (T2DM)
Overview
- Phase
- Phase 1
- Intervention
- AZD8601+Placebo (SAD)
- Conditions
- Male Subjects With Type II Diabetes (T2DM)
- Sponsor
- AstraZeneca
- Enrollment
- 44
- Locations
- 1
- Primary Endpoint
- Safety of AZD8601 by assessing summary of adverse events (Part A)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of signed and dated, written informed consent prior to any study specific procedures.
- •Male patients with mild T2DM aged 18 to 65 years with suitable veins for cannulation or repeated venipuncture.
- •Have a body mass index (BMI) between 20 and 35 kg/m2 inclusive and weigh at least 50 kg.
- •Able to understand, read and speak the German language.
- •T2DM diagnosis for at least 1 year at the time of the screening visit.
- •T2DM treated with diet and exercise alone or with up to 2 oral anti-diabetic drugs.
- •Have stable glycemic control indicated by no changed treatment within 3 months prior to enrolment.
- •Hemoglobin A1c less than 10.5% at screening (HbA1c value according to international Diabetes Control and Complications Trial standard).
- •Fasting plasma glucose ≤ 11.0 mmol/L at screening.
- •Provision of signed, written and dated informed consent for optional genetic/biomarker research.
Exclusion Criteria
- •History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study.
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the before Day -1
- •Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis results at screening and check-in, as judged by the PI.
- •The following strict criteria will apply at the time of screening and on Day -1:
- •Alanine aminotransferase (ALT), aspartate aminotransferase (AST) \> 2 times the upper limit of the normal laboratory range
- •Hemoglobin \< 11 g/dL and/or neutrophils \< 1500/mm3 and/or platelets \< 100 000/mm3
- •Creatinine \> 1.2 x upper limit of normal (ULN)
- •Uncontrolled or inadequately controlled hypertension at the time of screening and/or on Day -1 with a resting systolic or diastolic BP \> 150 mmHg or \> 95 mmHg, respectively. Patients with heart rate \< 50 bpm at screening and on Day -1 will be excluded.
- •Any clinically significant abnormalities on 12-lead ECG at screening as judged by the PI.
- •Any patient with QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 450 ms at screening should be excluded.
Arms & Interventions
Part A
Three cohorts with 9 subjects and each cohort received 2 treatments (AZD8601+Placebo/ Placebo+Placebo)
Intervention: AZD8601+Placebo (SAD)
Part A
Three cohorts with 9 subjects and each cohort received 2 treatments (AZD8601+Placebo/ Placebo+Placebo)
Intervention: Placebo+Placebo
Part B
Subjects received 2 treatments (AZD8601+Placebo)
Intervention: AZD8601+Placebo
Outcomes
Primary Outcomes
Safety of AZD8601 by assessing summary of adverse events (Part A)
Time Frame: Part A: From screening (Day -28) up to Day 29
To evaluate the safety by assessing the adverse event after administration of a single dose of AZD8601 to male subjects with T2DM (Part A).
Safety of AZD8601 by assessing number of subjects with Clinically significant 12-lead electrocardiograms (ECGs) (Part A)
Time Frame: Part A: Day 1 to Day 8
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).
Safety of AZD8601 by assessing number of subjects with clinically significant hematology parameters (Part A)
Time Frame: Part A: Day 1 to Day 8
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).
Safety of AZD8601 by assessing summary of adverse events (Part B)
Time Frame: Part B: From screening up to Day 15
To evaluate the safety by assessing the adverse event after administration of a single dose of AZD8601 to male subjects with T2DM (Part B).
Safety of AZD8601 by assessing number of subjects with clinically significant blood pressure (Part B)
Time Frame: Part B: Day 1 to Day 2
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).
Safety of AZD8601 by assessing number of subjects with clinically significant urinalysis (Part A)
Time Frame: Part A: Day 1 to Day 8
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).
Safety of AZD8601 by assessing number of subjects with clinically significant blood pressure (Part A)
Time Frame: Part A: Day 1 to Day 8
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).
Safety of AZD8601 by assessing number of subjects with Clinically significant pulse (Part A)
Time Frame: Part A: Day 1 to Day 8
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).
Safety of AZD8601 by assessing number of subjects with clinically significant clinical chemistry laboratory results (Part A)
Time Frame: Part A: Day 1 to Day 8
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).
Safety of AZD8601 by assessing number of subjects with Clinically significant pulse (Part B)
Time Frame: Part B: Day 1 to Day 2
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).
Safety of AZD8601 by assessing number of subjects with Clinically significant 12-lead electrocardiograms (ECGs) (Part B)
Time Frame: Part B: Day 1 to Day 2
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).
Safety of AZD8601 by assessing number of subjects with clinically significant hematology parameters (Part B)
Time Frame: Part B: Day 1 to Day 2
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).
Safety of AZD8601 by assessing number of subjects with clinically significant clinical chemistry laboratory results (Part B)
Time Frame: Part B: Day 1 to Day 2
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).
Safety of AZD8601 by assessing number of subjects with clinically significant urinalysis (Part B)
Time Frame: Part B: Day 1 to Day 2
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).