Assessment of the Safety, Tolerability and Pharmacodynamics After Administration of One Dose of AZD8601 to Male Patients With Type II Diabetes Mellitus (T2DM)

NCT02935712 | Completed Phase 1

• 2 other identifiers: D9150C000012016-002316-40
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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

Conditions

Male Subjects With Type II Diabetes (T2DM)

Keywords

Safety; Tolerability; AZD8601; Type II Diabetes

Outcome Measures

Primary Outcomes (14)

• 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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  Part B: Day 1 to Day 2

Study Arms (2)

Part A

EXPERIMENTAL

Three cohorts with 9 subjects and each cohort received 2 treatments (AZD8601+Placebo/ Placebo+Placebo)

Drug: AZD8601+Placebo (SAD); Drug: Placebo+Placebo

Part B

EXPERIMENTAL

Subjects received 2 treatments (AZD8601+Placebo)

Drug: AZD8601+Placebo

Interventions

AZD8601+Placebo (SAD) DRUG

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.

Part A

AZD8601+Placebo DRUG

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.

Part B

Placebo+Placebo DRUG

Subjects are randomized to receive 2 placebo treatments.

Part A

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), anti-hepatitis B core (HBc) antibody, hepatitis C antibody and human immunodeficiency virus (HIV) antibody.
• \. Current smokers or those who have smoked or used nicotine products within the previous 1 year cotinine below the cut-off of the local laboratory).
• \. Positive screen for drugs of abuse, cotinine or alcohol at screening or admission to the study center.
• \. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI.
• \. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/ acetaminophen), herbal remedies, mega-dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to admission or longer if the medication has a long half-life.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator
• Spandauer Damm 130: collaborator
• 14050: collaborator
• Berlin, Germany: collaborator

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sagittal Abdominal Diameter; Placebo Effect

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena; Effect Modifier, Epidemiologic; Epidemiologic Factors; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Rainard Fuhr, Dr. med.

  Early Phase Clinical Unit, PAREXEL International GmbH, Berlin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2016
• First Posted: October 17, 2016
• Study Start: December 16, 2016
• Primary Completion: August 4, 2017
• Study Completion: January 8, 2018
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

DE (1)