A Phase I, Safety Tolerability and Pharmacokinetics of AZD4831 to Treat Cardiovascular Disease

• Status: Completed
• Trial end date: 2017-11-22
• Target enrollment: 0
• Participant gender: Male

Summary

This is a Phase I study to investigate the safety and tolerability of AZD4831 in healthy male participants, conducted at a single center. The results from this study will form the basis for decisions on future studies. Another purpose of this dose escalation study is to find out the right dose of the experimental drug to be given to study participants in future studies. Even though there were no harmful effects seen in the animals tested, investigator does not know what side effects the experimental drug might cause in humans. However, site personnel managing the study participants will be blinded to the extent possible and as long as possible to minimize any impact on data collection. Study participants will be blinded to treatment allocation.

The study will be conducted in healthy participants to avoid interference from disease processes or other drugs.

The participants will stay at the study center during the whole dosing period and until 48 hours post final dose.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: AstraZeneca
• Collaborator: Parexel

Criteria

Inclusion Criteria:

• Healthy male participants aged 18 to 50 years (inclusive at Screening) with suitable veins for cannulation or repeated venipuncture.

• Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.

Exclusion Criteria:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.

• History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.

• Presence of infection(s) (particularly fungal infection), as judged by the Investigator.

• History or current thyroid disease.

• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.

• Any clinically significant abnormalities in biochemistry, hematology, or urinalysis results, as judged by the Investigator at Screening and/or Day 1, including

1. Alanine aminotransferase (ALT) not within normal range;

2. Aspartate aminotransferase (AST) not within normal range;

3. Creatinine not within normal range;

4. White blood cell (WBC) not within normal range;

5. Hemoglobin not within normal range; and

6. Estimated Glomerular Filtration Rate (eGFR) not within normal range.

• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) type 1 and 2.

• Abnormal vital signs, after 10 minutes supine rest, at Screening and/or Day 1, defined as any of the following:

1. Systolic BP (SBP) < 90 mmHg or ≥ 140 mmHg

2. Diastolic BP (DBP) < 50 mmHg or ≥ 90 mmHg

3. Pulse < 45 or > 85 beats per minute (bpm)

• Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or interventricular conduction delay with QRS > 110 ms. Participants with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of, for example, ventricular hypertrophy or pre-excitation at Screening and/or Day 1.

• Electrocardiogram findings suggesting a metabolic or other non-cardiac condition that may confound interpretation of serial changes (such as hypokalemia) at Screening and/or Day 1.

• Use of any prescribed or non-prescribed medication (other than paracetamol/acetaminophen), including antacids, analgesics, herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks before the first administration of IMP or longer if the medication has a long half-life.

• Plasma donation within 1 month of Screening or any blood donation/blood loss > 500 mL during the 3 months before Screening.

• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest.

• Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.