HypercholesterolemiaPhase 1NCT03593785
A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD8233 in Healthy Male Subjects With Increased Elevated LDL-C Levels.
A Phase 1 study testing AZD8233 in people with Hypercholesterolemia, run by AstraZeneca at 1 site in United States.
Trial summary
AZD8233 has not been evaluated in clinical studies previously. This is a first-in-human (FiH) study. This study will assess the safety, tolerability and pharmacokinetics (PK) of AZD8233, following subcutaneous (SC) administration of single ascending dose (SAD) of AZD8233. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- AZD8233
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Aug 2018to 19 Dec 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provision of signed and dated, written informed consent before any study specific procedures.
- Healthy male subjects aged 18 to 60 years (inclusive at Screening Visit) with suitable veins for cannulation or repeated venipuncture.
- Have a body mass index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 60 kg and no more than 100 kg inclusive at the Screening Visit and Day -1.
- Have a LDL-C ≥ 100 mg/dL < 190 mg/dL at the Screening Visit and Day -1, test may be repeated once for each visit at the discretion of the Investigator if out of the range.
- Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.
Who cannot join
- History of any clinically important 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 GI, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
- Any clinically important illness, medical/surgical procedure or trauma within 4weeks of the first administration of IMP.
- Any laboratory values with the following deviations at the Screening Visit and/or Day -1, test may be repeated once for each visit at the discretion of the Investigator if out of range:
- 4.1.Alanine aminotransferase (ALT)> upper limit of normal (ULN). 4.2.Aspartate aminotransferase (AST)> ULN. 4.3.Creatinine > ULN. 4.4.White blood cell (WBC)< LLN. 4.5.Hemoglobin< LLN. 4.6.Platelet count ≤150000/μL. 4.7.Activated partial thrombin time greater than ULN and PT greater than ULN. 4.8.Have an eGFR < 60mL/min. 4.9.Have an urinary albumin-to-creatinine ratio(ACR)> 3mg/μmol (30mg/g).
- Any other clinically important abnormalities in clinical chemistry, hematology or urinalysis results, than those described under exclusion criterion number 4, as judged by the Investigator.
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- Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV).
- Abnormal vital signs, after 10 minutes supine rest, with the following deviations at the Screening Visit and/or Day -1, test may be repeated once for each visit at the discretion of the Investigator if out of range:
- 7.1.Systolic BP< 90mmHgor> 140mmHg. 7.2.Diastolic BP< 50mmHgor > 90mmHg. 7.3.Heart rate < 45 or > 85 beats per minute(bpm).
- Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12 Lead ECG as considered by the Investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy at the Screening Visit or Day -1, test may be repeated once for each visit, at the discretion of the Investigator if out of range.
- 8.1. Prolonged QTcF > 450 ms. 8.2. Shortened QTcF < 340 ms. 8.3. Family history of long QT syndrome. 8.4. PR (PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation).
- 8.5. PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree atrioventricular (AV) block, or AV dissociation.
- 8.6. Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS > 110 ms. Subjects with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of e.g., ventricular hypertrophy or pre-excitation.
- Known or suspected history of drug abuse as judged by the Investigator.
- Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 3 months before the Screening Visit.
- History of alcohol abuse or excessive intake of alcohol as judged by the Investigator.
- Positive screen for drugs of abuse, alcohol, or cotinine (nicotine) at the Screening Visit or positive screen for drugs of abuse or alcohol, on admission to the Clinical Unit.
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD8233.
- Excessive intake of caffeine-containing drinks or food (e.g., coffee, tea, chocolate,) as judged by the Investigator.
- Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks before the first administration of IMP.
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times t he 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 the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months before the Screening Visit.
- 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. Note: subjects consented and screened, but not randomized in this study or a previous Phase 1 study, are not excluded.
- Involvement of any Astra Zeneca or study site employee or their close relatives.
- Judgment by the Investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the Screening Period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
- Subjects who are vegans or have medical dietary restrictions.
- Subjects who cannot communicate reliably with the Investigator.
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
- Previous bone marrow transplant.
- Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD8233 Following Single Ascending Dose Administration to Healthy Male Subjects With Elevated LDL-C Levels.
AZD8233 has not been evaluated in clinical studies previously. This is a first-in-human (FiH) study. This study will assess the safety, tolerability and pharmacokinetics (PK) of AZD8233, following subcutaneous (SC) administration of single ascending dose (SAD) of AZD8233. This study will also investigate the pharmacodynamics (PD) of AZD8233 by investigating the effect of AZD8233 on levels of cholesterol and related biomarkers.
Read the detailed description
This randomized, single-blind, placebo-controlled study will be conducted at a single study center in United States of America. Up to 56 healthy male subjects with elevated LDL-C levels, aged 18 to 60 years will be randomized into this study. This study will consist of 5 cohorts with 8 subjects in each. Depending on emerging data, 2 additional cohorts may be added to test additional dose levels at the discretion of the sponsor, if the pre-defined exposure limits and stopping criteria have not been reached at previous administered doses. The study will comprise of 3 periods:
- A screening period of maximum 28 days.
- A treatment period:
- A follow-up period of 16 weeks
In each cohort, 6 subjects will be randomized to receive a single SC dose of AZD8233 and 2 subjects randomized to receive placebo. Single dose of AZD8233 SC injection (40 mg/mL) will be administered in each cohort as follows:
Cohort 1: Dose 1 (starting dose) Cohort 2: Dose 2 (provisional dose) Cohort 3: Dose 3 (provisional dose) Cohort 4: Dose 4 (provisional dose) Cohort 5: Dose 5 (provisional dose) Dosing for each ascending dose cohort will proceed with 2 subjects in a sentinel cohort, such that 1 subject will be randomized to receive placebo and 1 subject will be randomized to receive AZD8233.
In the treatment period, the sentinel and non-sentinel subjects will be resident at the clinical unit from the day before IMP administration (Day -1) until at least 72 hours and 48 hours after IMP administration, respectively.
Sentinel will have 10 follow-up visits (1, 2, 3, 4, 6, 8, 10, 12, 14 and 16 weeks post-dose). Non-sentinel subjects will have 11 follow-up visits (on Day 4 and 1, 2, 3, 4, 6, 8, 10, 12, 14 and 16 weeks post-dose).
The follow-up period (16 weeks) has been selected based on the predicted terminal half-life of AZD8233 in man (predicted to be 2 to 3 weeks), to cover at least 5 half-lives.
Following review of data from the study, the Safety Review Committee (SRC) may decide to:
- Adjust the window for sentinel dosing.
- Adjust the length of data collection prior to dose-escalation diction.
- Prolong the length of the stay at the Clinical Unit.
- Adjust the timing and number of assessments and/or blood/urine samples for subsequent cohorts.
- Adjust the length of the Follow-up Period. Each subject will be involved in the study for up to 20 weeks.
- Conditions
- Hypercholesterolemia
- Being tested
- AZD8233
- Keywords
- Cholesterol, Biomarkers
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD8233Drug
Randomized subjects will receive single SC dose of AZD8233 (dose 1, dose 2, dose 3, dose 4 and dose 5) injection.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | On Day 1, randomized subjects will receive single SC dose of AZD8233 dose 1 injection (6 subjects) or matching placebo (2 subjects). Receives: Drug: AZD8233 |
| Cohort 2 | Experimental | On Day 1, randomized subjects will receive single SC dose of AZD8233 dose 2 injection (6 subjects) or matching placebo (2 subjects). Receives: Drug: AZD8233 |
| Cohort 3 | Experimental | On Day 1, randomized subjects will receive single SC dose of AZD8233 dose 3 injection (6 subjects) or matching placebo (2 subjects). Receives: Drug: AZD8233 |
| Cohort 4 | Experimental | On Day 1, randomized subjects will receive single SC dose of AZD8233 dose 4 injection (6 subjects) or matching placebo (2 subjects). Receives: Drug: AZD8233 |
| Cohort 5 | Experimental | On Day 1, randomized subjects will receive single SC dose of AZD8233 dose 5 injection (6 subjects) or matching placebo (2 subjects). Receives: Drug: AZD8233 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with adverse events (AEs) due to AZD8233 SC SAD treatment
To assess AEs as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. Serious AEs will be recorded from the time of informed consent.
Measured: From randomization to 4 months follow-up
Vital sign: Blood pressure [BP]
To assess supine position systolic and diastolic BP as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. Both SBP and DBP will be collected after the subject has rested in the supine position for at least 10 minutes.
Measured: From screening to 4 month follow-up.
Vital sign: Pulse rate
To assess supine position pulse rate as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. Pulse rate will be collected after the subject has rested in the supine position for at least 10 minutes.
Measured: From screening to 4 month follow-up.
Vital sign: Oral body temperature
To assess oral body temperature as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. Body temperature will be collected after the subject has rested in the supine position for at least 10 minutes.
Measured: From screening to 4 month follow-up.
Number of patients with abnormal findings in Resting 12-lead Electrocardiogram (ECG)
To assess any clinically significant abnormalities in the cardiovascular system functioning using a 12-lead ECG as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. ECG evaluations will be recorded after approximately 10 min resting in supine position.
Measured: From screening to 4 month follow-up.
Physical examination
To assess physical examination as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. Full (general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck [including ears, eyes, nose, and throat], lymph nodes, thyroid, musculoskeletal and neurological systems) and brief (Abbreviated; general appearance, skin, cardiovascular system, respiratory and abdomen) physical examinations will be performed.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Haematology - Blood cells count
To assess red blood cells ( RBC) and white blood cells (WBC) count as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Haematology - Hemoglobin (Hb)
To assess Hb as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Haematology - Haematocrit (HCT)
To assess HCT (volume percentage of RBC in blod) as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Haematology - Mean corpuscular volume (MCV)
To assess MCV as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Haematology - Mean corpuscular hemoglobin (MCH)
To assess MCH as a variable of safety and tolerability following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Haematology - Mean corpuscular hemoglobin concentration (MCHC)
To assess MCHC as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Haematology - Differential count
To assess differential WBC count absolute count of neutrophils, lymphocytes, monocytes, eosinophils and basophils as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Haematology - Platelets
To assess platelets count as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Haematology - Reticulocytes absolute count
To assess reticulocytes absolute count as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Serum clinical chemistry - Electrolytes
To assess serum level of sodium, potassium, calcium and phosphate as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Serum clinical chemistry - Urea
To assess serum level of urea as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Serum clinical chemistry - Creatinine
To assess serum level of creatinine as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Serum clinical chemistry - Glucose (fasting)
To assess serum fasting glucose level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Serum clinical chemistry - Liver enzymes
To assess serum of Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Gamma glutamyl transpeptidase (GGT) as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Serum clinical chemistry - Total Bilirubin
To assess serum bilirubin (total) level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Serum clinical chemistry - Cell enzymes
To assess serum glutamate dehydrogenase and lactate dehydrogenase level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Coagulation
To assess activated partial thrombin time (aPTT) and prothrombin time (PT) as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Lipid Panel
To assess serum level of high density lipoprotein, low density lipoprotein, triglycerides and total cholesterol as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Clinical Urinalysis - Glucose
To assess urine glucose level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Clinical Urinalysis - Protein
To assess urine protein level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Clinical Urinalysis - Blood
To assess presence of blood in urine as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Clinical Urinalysis - Creatinine
To assess urine creatinine level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Clinical Urinalysis - Microscopy evaluation
If protein or blood present in urine, levels of RBC, WBC, Casts (Cellular, Granular, Hyaline) will be assessed as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Renal Safety Biomarkers - Serum Creatinine
To assess renal biomarker by evaluation of serum creatinine level, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Renal Safety Biomarkers - Urine protein
To assess renal biomarker by evaluation of urine protein level, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Renal Safety Biomarkers - Estimated glomerular filtration rate (eGFR)
To assess renal biomarker by evaluation of eGFR, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Renal Safety Biomarkers -Urine Kidney Injury Molecule-1 (KIM-1)
To assess renal biomarker by evaluation of urine KIM-1 level, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Renal Safety Biomarkers - Urine Neutrophil gelatinase-associated lipocalin (NGAL)
To assess renal biomarker by evaluation of NGAL level in urine, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Renal Safety Biomarkers - Urine Alpha-glutathione S-transferase (Alpha-GST)
To assess renal biomarker by evaluation of Alpha-GST level in urine, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Immune Activation Response: High Sensitivity - C-reactive protein (hs-CRP)
To assess hs-CRP level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: Days 1 to 3 (pre-dose, 2, 4, 24 and 48 hours post-dose).
Complement Activation panel
To assess chemotactic factors (C3a, C5a and Bp) levels as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: Day -1 and Days 1 to 3 (2, 4 and 24 hours post-dose).
Injection Site Reaction Examinations
To assess injection site reactions in terms of size (mm), color (pale/light red/dark red) and itching (yes or no) as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: At Days 1 to 4, week 1 to 14 and week 16.
Number of patients with abnormal findings in Telemetry
To assess heart rhythm and QRS pattern (heart conduction) as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. ECG evaluations will be recorded after approximately 10 min resting in supine position.
Measured: At Day -1 and Days 1 to 3 (Pre-dose to 24 hours post-dose)
Laboratory assessments: Serum clinical chemistry - Creatine kinase
To assess serum level of creatine kinase as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Serum clinical chemistry - Bicarbonate
To assess serum level of Bicarbonate as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Serum clinical chemistry - Direct bilirubin
To assess serum level of direct bilirubin as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Laboratory assessments: Serum clinical chemistry -Uric acid
To assess serum level of Uric acid as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Measured: From screening to 4 month follow-up.
Secondary outcomes (17)
Plasma PK analysis: Time delay between drug administration and the first observed concentration in plasma (tlag)
To characterize tlag of AZD8233 following SC administration of SAD.
Measured: At treatment Days 1 to 3 (Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Time to reach peak or maximum observed concentration following drug administration (tmax)
To characterize tmax of AZD8233 following SC administration of SAD.
Measured: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Maximum observed plasma concentration (Cmax)
To characterize Cmax of AZD8233 following SC administration of SAD.
Measured: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUC[0-last])
To characterize AUC(0-last) of AZD8233 following SC administration of SAD.
Measured: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Area under the concentration-time curve from time zero to 48 hours post-dose (AUC[0-48])
To characterize AUC(0-48) of AZD8233 following SC administration of SAD.
Measured: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Area under the concentration-time curve from time zero extrapolated to infinity (AUC)
To characterize AUC of AZD8233 following SC administration of SAD. AUC is estimated by AUC(0-last) + Clast/λz where Clast is the last observed quantifiable concentration.
Measured: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
To characterize CL/F of AZD8233 following SC administration of SAD.
Measured: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Apparent volume of distribution for parent drug at terminal phase (extravascular administration) (Vz/F)
To characterize Vz/F of AZD8233 following SC administration of SAD; estimated by dividing the apparent clearance (CL/F) by λz.
Measured: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Half-life associated with the terminal slope (λz) of a semi-logarithmic concentration-time curve (t½z)
To characterize t½z of AZD8233 following SC administration of SAD.
Measured: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Mean Residence Time (MRT)
To characterize MRT of AZD8233 following SC administration of SAD.
Measured: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Urine PK analysis: Amount of analyte excreted unchanged in urine from time t1 to t2 (Ae[t1-t2])
To characterize Ae(t1-t2) of AZD8233 following SC administration of SAD.
Measured: Treatment Days 1 to 3 (Pre-dose, 0-6, 6-12, 12-24, 24-36 and 36-48 hours post-dose)
Urine PK analysis: Cumulative amount of analyte excreted at the last sampling interval (Ae[0-last])
To characterize Ae(0-last) of AZD8233 following SC administration of SAD.
Measured: Treatment Days 1 to 3 (Pre-dose, 0-6, 6-12, 12-24, 24-36 and 36-48 hours post-dose)
Urine PK analysis: Fraction of analyte excreted unchanged in urine from t1 to t2 (fe[t1-t2])
To characterize fe(t1-t2) of AZD8233 following SC administration of SAD.
Measured: Treatment Days 1 to 3 (Pre-dose, 0-6, 6-12, 12-24, 24-36 and 36-48 hours post-dose)
Urine PK analysis: Cumulative fraction of dose excreted unchanged into the urine from time zero to the last measured time-point for an analyte (fe[0-last])
To characterize fe(0-last) of AZD8233 following SC administration of SAD; estimated by dividing Ae(0-last) by dose.
Measured: Treatment Days 1 to 3 (Pre-dose, 0-6, 6-12, 12-24, 24-36 and 36-48 hours post-dose)
Urine PK analysis: Percentage of dose excreted unchanged into the urine from time zero to the last measured time-point for an analyte (%fe[0-last])
To characterize %fe(0-last) of AZD8233 following SC administration of SAD; estimated by dividing Ae(0-last) by dose.
Measured: Treatment Days 1 to 3 (Pre-dose, 0-6, 6-12, 12-24, 24-36 and 36-48 hours post-dose)
Urine PK analysis: Renal clearance of drug from plasma (CLR)
To characterize CLR of AZD8233 following SC administration of SAD; estimated by dividing Ae(0-48) by AUC(0-48).
Measured: Treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose)
PD analysis: The effect of AZD8233 on cholesterol and related biomarkers
To assess the effect of AZD8233 on a PD variable (cholesterol and related biomarkers) following SC administration of single ascending doses. The results will be listed and summarized by treatment (dose level of AZD8233 or pooled placebo) including changes from baseline.
Measured: At screening, Day -1, Days 1 to 3 (pre-dose and 24 hours post-dose), Day 4 (72 hours post-dose), week 1 to 14 (at 1, 2, 3, 4, 6, 8, 10 and 12 weeks post-dose) and final follow-up visit/ET visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2018
- Study start3 Aug 2018
- Primary completion19 Dec 2020
- Study completion19 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- David Han, M.D, Principal investigator, PAREXEL Early Phase Clinical Unit-Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03593785
- Sponsor's protocol ID
- D7990C00001
- Status last verified
- Jan 2021
- First submitted
- 10 Jul 2018
- Last updated
- 25 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD8233 Following Single Ascending Dose Administration to Healthy Male Subjects With Elevated LDL-C Levels.
- ClinicalTrials.gov ID
- NCT03593785
- Acronym / sponsor ID
- D7990C00001
- Conditions
- Hypercholesterolemia
- Keywords
- Cholesterol, Biomarkers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 3 Aug 2018 (actual)
- Primary completion
- 19 Dec 2020 (actual)
- Study completion
- 19 Dec 2020 (actual)
- First posted
- 20 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
AZD8233 has not been evaluated in clinical studies previously. This is a first-in-human (FiH) study. This study will assess the safety, tolerability and pharmacokinetics (PK) of AZD8233, following subcutaneous (SC) administration of single ascending dose (SAD) of AZD8233. This study will also investigate the pharmacodynamics (PD) of AZD8233 by investigating the effect of AZD8233 on levels of cholesterol and related biomarkers.
Detailed description
This randomized, single-blind, placebo-controlled study will be conducted at a single study center in United States of America. Up to 56 healthy male subjects with elevated LDL-C levels, aged 18 to 60 years will be randomized into this study. This study will consist of 5 cohorts with 8 subjects in each. Depending on emerging data, 2 additional cohorts may be added to test additional dose levels at the discretion of the sponsor, if the pre-defined exposure limits and stopping criteria have not been reached at previous administered doses. The study will comprise of 3 periods:
- A screening period of maximum 28 days.
- A treatment period:
- A follow-up period of 16 weeks
In each cohort, 6 subjects will be randomized to receive a single SC dose of AZD8233 and 2 subjects randomized to receive placebo. Single dose of AZD8233 SC injection (40 mg/mL) will be administered in each cohort as follows:
Cohort 1: Dose 1 (starting dose) Cohort 2: Dose 2 (provisional dose) Cohort 3: Dose 3 (provisional dose) Cohort 4: Dose 4 (provisional dose) Cohort 5: Dose 5 (provisional dose) Dosing for each ascending dose cohort will proceed with 2 subjects in a sentinel cohort, such that 1 subject will be randomized to receive placebo and 1 subject will be randomized to receive AZD8233.
In the treatment period, the sentinel and non-sentinel subjects will be resident at the clinical unit from the day before IMP administration (Day -1) until at least 72 hours and 48 hours after IMP administration, respectively.
Sentinel will have 10 follow-up visits (1, 2, 3, 4, 6, 8, 10, 12, 14 and 16 weeks post-dose). Non-sentinel subjects will have 11 follow-up visits (on Day 4 and 1, 2, 3, 4, 6, 8, 10, 12, 14 and 16 weeks post-dose).
The follow-up period (16 weeks) has been selected based on the predicted terminal half-life of AZD8233 in man (predicted to be 2 to 3 weeks), to cover at least 5 half-lives.
Following review of data from the study, the Safety Review Committee (SRC) may decide to:
- Adjust the window for sentinel dosing.
- Adjust the length of data collection prior to dose-escalation diction.
- Prolong the length of the stay at the Clinical Unit.
- Adjust the timing and number of assessments and/or blood/urine samples for subsequent cohorts.
- Adjust the length of the Follow-up Period. Each subject will be involved in the study for up to 20 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: AZD8233On Day 1, randomized subjects will receive single SC dose of AZD8233 dose 1 injection (6 subjects) or matching placebo (2 subjects). |
| Cohort 2 | Experimental | Drug: AZD8233On Day 1, randomized subjects will receive single SC dose of AZD8233 dose 2 injection (6 subjects) or matching placebo (2 subjects). |
| Cohort 3 | Experimental | Drug: AZD8233On Day 1, randomized subjects will receive single SC dose of AZD8233 dose 3 injection (6 subjects) or matching placebo (2 subjects). |
| Cohort 4 | Experimental | Drug: AZD8233On Day 1, randomized subjects will receive single SC dose of AZD8233 dose 4 injection (6 subjects) or matching placebo (2 subjects). |
| Cohort 5 | Experimental | Drug: AZD8233On Day 1, randomized subjects will receive single SC dose of AZD8233 dose 5 injection (6 subjects) or matching placebo (2 subjects). |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Provision of signed and dated, written informed consent before any study specific procedures.
- Healthy male subjects aged 18 to 60 years (inclusive at Screening Visit) with suitable veins for cannulation or repeated venipuncture.
- Have a body mass index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 60 kg and no more than 100 kg inclusive at the Screening Visit and Day -1.
- Have a LDL-C ≥ 100 mg/dL < 190 mg/dL at the Screening Visit and Day -1, test may be repeated once for each visit at the discretion of the Investigator if out of the range.
- Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.
Key exclusion criteria (31 listed)
- History of any clinically important 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 GI, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
- Any clinically important illness, medical/surgical procedure or trauma within 4weeks of the first administration of IMP.
- Any laboratory values with the following deviations at the Screening Visit and/or Day -1, test may be repeated once for each visit at the discretion of the Investigator if out of range:
- 4.1.Alanine aminotransferase (ALT)> upper limit of normal (ULN). 4.2.Aspartate aminotransferase (AST)> ULN. 4.3.Creatinine > ULN. 4.4.White blood cell (WBC)< LLN. 4.5.Hemoglobin< LLN. 4.6.Platelet count ≤150000/μL. 4.7.Activated partial thrombin time greater than ULN and PT greater than ULN. 4.8.Have an eGFR < 60mL/min. 4.9.Have an urinary albumin-to-creatinine ratio(ACR)> 3mg/μmol (30mg/g).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD8233Randomized subjects will receive single SC dose of AZD8233 (dose 1, dose 2, dose 3, dose 4 and dose 5) injection. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
Primary outcome
Number of subjects with adverse events (AEs) due to AZD8233 SC SAD treatment
Time frame: From randomization to 4 months follow-up
To assess AEs as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. Serious AEs will be recorded from the time of informed consent.
Vital sign: Blood pressure [BP]
Time frame: From screening to 4 month follow-up.
To assess supine position systolic and diastolic BP as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. Both SBP and DBP will be collected after the subject has rested in the supine position for at least 10 minutes.
Vital sign: Pulse rate
Time frame: From screening to 4 month follow-up.
To assess supine position pulse rate as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. Pulse rate will be collected after the subject has rested in the supine position for at least 10 minutes.
Vital sign: Oral body temperature
Time frame: From screening to 4 month follow-up.
To assess oral body temperature as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. Body temperature will be collected after the subject has rested in the supine position for at least 10 minutes.
Number of patients with abnormal findings in Resting 12-lead Electrocardiogram (ECG)
Time frame: From screening to 4 month follow-up.
To assess any clinically significant abnormalities in the cardiovascular system functioning using a 12-lead ECG as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. ECG evaluations will be recorded after approximately 10 min resting in supine position.
Physical examination
Time frame: From screening to 4 month follow-up.
To assess physical examination as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. Full (general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck [including ears, eyes, nose, and throat], lymph nodes, thyroid, musculoskeletal and neurological systems) and brief (Abbreviated; general appearance, skin, cardiovascular system, respiratory and abdomen) physical examinations will be performed.
Laboratory assessments: Haematology - Blood cells count
Time frame: From screening to 4 month follow-up.
To assess red blood cells ( RBC) and white blood cells (WBC) count as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Haematology - Hemoglobin (Hb)
Time frame: From screening to 4 month follow-up.
To assess Hb as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Haematology - Haematocrit (HCT)
Time frame: From screening to 4 month follow-up.
To assess HCT (volume percentage of RBC in blod) as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Haematology - Mean corpuscular volume (MCV)
Time frame: From screening to 4 month follow-up.
To assess MCV as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Haematology - Mean corpuscular hemoglobin (MCH)
Time frame: From screening to 4 month follow-up.
To assess MCH as a variable of safety and tolerability following SC administration of single ascending doses.
Laboratory assessments: Haematology - Mean corpuscular hemoglobin concentration (MCHC)
Time frame: From screening to 4 month follow-up.
To assess MCHC as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Haematology - Differential count
Time frame: From screening to 4 month follow-up.
To assess differential WBC count absolute count of neutrophils, lymphocytes, monocytes, eosinophils and basophils as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Haematology - Platelets
Time frame: From screening to 4 month follow-up.
To assess platelets count as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Haematology - Reticulocytes absolute count
Time frame: From screening to 4 month follow-up.
To assess reticulocytes absolute count as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Serum clinical chemistry - Electrolytes
Time frame: From screening to 4 month follow-up.
To assess serum level of sodium, potassium, calcium and phosphate as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Serum clinical chemistry - Urea
Time frame: From screening to 4 month follow-up.
To assess serum level of urea as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Serum clinical chemistry - Creatinine
Time frame: From screening to 4 month follow-up.
To assess serum level of creatinine as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Serum clinical chemistry - Glucose (fasting)
Time frame: From screening to 4 month follow-up.
To assess serum fasting glucose level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Serum clinical chemistry - Liver enzymes
Time frame: From screening to 4 month follow-up.
To assess serum of Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Gamma glutamyl transpeptidase (GGT) as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Serum clinical chemistry - Total Bilirubin
Time frame: From screening to 4 month follow-up.
To assess serum bilirubin (total) level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Serum clinical chemistry - Cell enzymes
Time frame: From screening to 4 month follow-up.
To assess serum glutamate dehydrogenase and lactate dehydrogenase level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Coagulation
Time frame: From screening to 4 month follow-up.
To assess activated partial thrombin time (aPTT) and prothrombin time (PT) as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Lipid Panel
Time frame: From screening to 4 month follow-up.
To assess serum level of high density lipoprotein, low density lipoprotein, triglycerides and total cholesterol as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Clinical Urinalysis - Glucose
Time frame: From screening to 4 month follow-up.
To assess urine glucose level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Clinical Urinalysis - Protein
Time frame: From screening to 4 month follow-up.
To assess urine protein level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Clinical Urinalysis - Blood
Time frame: From screening to 4 month follow-up.
To assess presence of blood in urine as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Clinical Urinalysis - Creatinine
Time frame: From screening to 4 month follow-up.
To assess urine creatinine level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Clinical Urinalysis - Microscopy evaluation
Time frame: From screening to 4 month follow-up.
If protein or blood present in urine, levels of RBC, WBC, Casts (Cellular, Granular, Hyaline) will be assessed as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Renal Safety Biomarkers - Serum Creatinine
Time frame: From screening to 4 month follow-up.
To assess renal biomarker by evaluation of serum creatinine level, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Renal Safety Biomarkers - Urine protein
Time frame: From screening to 4 month follow-up.
To assess renal biomarker by evaluation of urine protein level, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Renal Safety Biomarkers - Estimated glomerular filtration rate (eGFR)
Time frame: From screening to 4 month follow-up.
To assess renal biomarker by evaluation of eGFR, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Renal Safety Biomarkers -Urine Kidney Injury Molecule-1 (KIM-1)
Time frame: From screening to 4 month follow-up.
To assess renal biomarker by evaluation of urine KIM-1 level, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Renal Safety Biomarkers - Urine Neutrophil gelatinase-associated lipocalin (NGAL)
Time frame: From screening to 4 month follow-up.
To assess renal biomarker by evaluation of NGAL level in urine, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Renal Safety Biomarkers - Urine Alpha-glutathione S-transferase (Alpha-GST)
Time frame: From screening to 4 month follow-up.
To assess renal biomarker by evaluation of Alpha-GST level in urine, as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Immune Activation Response: High Sensitivity - C-reactive protein (hs-CRP)
Time frame: Days 1 to 3 (pre-dose, 2, 4, 24 and 48 hours post-dose).
To assess hs-CRP level as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Complement Activation panel
Time frame: Day -1 and Days 1 to 3 (2, 4 and 24 hours post-dose).
To assess chemotactic factors (C3a, C5a and Bp) levels as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Injection Site Reaction Examinations
Time frame: At Days 1 to 4, week 1 to 14 and week 16.
To assess injection site reactions in terms of size (mm), color (pale/light red/dark red) and itching (yes or no) as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Number of patients with abnormal findings in Telemetry
Time frame: At Day -1 and Days 1 to 3 (Pre-dose to 24 hours post-dose)
To assess heart rhythm and QRS pattern (heart conduction) as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses. ECG evaluations will be recorded after approximately 10 min resting in supine position.
Laboratory assessments: Serum clinical chemistry - Creatine kinase
Time frame: From screening to 4 month follow-up.
To assess serum level of creatine kinase as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Serum clinical chemistry - Bicarbonate
Time frame: From screening to 4 month follow-up.
To assess serum level of Bicarbonate as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Serum clinical chemistry - Direct bilirubin
Time frame: From screening to 4 month follow-up.
To assess serum level of direct bilirubin as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
Laboratory assessments: Serum clinical chemistry -Uric acid
Time frame: From screening to 4 month follow-up.
To assess serum level of Uric acid as a variable of safety and tolerability of AZD8233 following SC administration of single ascending doses.
17 secondary outcomes
Plasma PK analysis: Time delay between drug administration and the first observed concentration in plasma (tlag)
Time frame: At treatment Days 1 to 3 (Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Time to reach peak or maximum observed concentration following drug administration (tmax)
Time frame: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Maximum observed plasma concentration (Cmax)
Time frame: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUC[0-last])
Time frame: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Area under the concentration-time curve from time zero to 48 hours post-dose (AUC[0-48])
Time frame: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Area under the concentration-time curve from time zero extrapolated to infinity (AUC)
Time frame: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
Time frame: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Apparent volume of distribution for parent drug at terminal phase (extravascular administration) (Vz/F)
Time frame: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Half-life associated with the terminal slope (λz) of a semi-logarithmic concentration-time curve (t½z)
Time frame: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Plasma PK analysis: Mean Residence Time (MRT)
Time frame: At treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose); Day 4 (72 hours post-dose); week 1 to 14 (at 1, 2, 4, 6, 8 and 12 weeks post-dose) and Final Follow-up Visit/ET Visit
Urine PK analysis: Amount of analyte excreted unchanged in urine from time t1 to t2 (Ae[t1-t2])
Time frame: Treatment Days 1 to 3 (Pre-dose, 0-6, 6-12, 12-24, 24-36 and 36-48 hours post-dose)
Urine PK analysis: Cumulative amount of analyte excreted at the last sampling interval (Ae[0-last])
Time frame: Treatment Days 1 to 3 (Pre-dose, 0-6, 6-12, 12-24, 24-36 and 36-48 hours post-dose)
Urine PK analysis: Fraction of analyte excreted unchanged in urine from t1 to t2 (fe[t1-t2])
Time frame: Treatment Days 1 to 3 (Pre-dose, 0-6, 6-12, 12-24, 24-36 and 36-48 hours post-dose)
Urine PK analysis: Cumulative fraction of dose excreted unchanged into the urine from time zero to the last measured time-point for an analyte (fe[0-last])
Time frame: Treatment Days 1 to 3 (Pre-dose, 0-6, 6-12, 12-24, 24-36 and 36-48 hours post-dose)
Urine PK analysis: Percentage of dose excreted unchanged into the urine from time zero to the last measured time-point for an analyte (%fe[0-last])
Time frame: Treatment Days 1 to 3 (Pre-dose, 0-6, 6-12, 12-24, 24-36 and 36-48 hours post-dose)
Urine PK analysis: Renal clearance of drug from plasma (CLR)
Time frame: Treatment Days 1 to 3 (Pre-dose and then at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose)
PD analysis: The effect of AZD8233 on cholesterol and related biomarkers
Time frame: At screening, Day -1, Days 1 to 3 (pre-dose and 24 hours post-dose), Day 4 (72 hours post-dose), week 1 to 14 (at 1, 2, 3, 4, 6, 8, 10 and 12 weeks post-dose) and final follow-up visit/ET visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2021.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Han, M.D principal investigator
PAREXEL Early Phase Clinical Unit-Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD8233 in people with Hypercholesterolemia, run by AstraZeneca at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects with adverse events (AEs) due to AZD8233 SC SAD treatment (time frame: From randomization to 4 months follow-up). The study lists 43 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2021.