DyslipidemiaPhase 1NCT04155645

To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD8233 After Multiple Dose Administration in Subjects With Dyslipidemia

A Phase 1 study testing AZD8233 subcutaneous injection in people with Dyslipidemia, run by AstraZeneca at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a Phase I study to assess the safety, tolerability and pharmacokinetics (PK), and pharmacodynamics (PD) of AZD8233, following subcutaneous (SC) administration of multiple ascending doses (MAD) of AZD8233 in subjects with confirmed dyslipidemia with or without type 2 diabetes. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Dyslipidemia
What is being tested?: AZD8233 subcutaneous injection
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 34 participants
Where: 7 sitesUnited States
Study dates: 21 Nov 2019to 7 Jun 2021
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Provision of signed and dated, written informed consent before any study specific procedures.
Must be willing and able to comply with all required study procedures.
Male or female subjects aged 18 to 65 years at signing of informed consent.
Females must not be pregnant and must have a negative urine pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating; or must be of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria:
Postmenopausal defined as 12 months with no menses without an alternative medical cause.
Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.

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Have suitable veins for cannulation or repeated venipuncture.
Have a body mass index between 25 and 40 kg/m2.
Have a Low-density lipoprotein (LDL) cholesterol > 70 but <190 mg/dL (4.9 mmol/L).
Calculated glomerular filtration rate > 60 mL/min by estimated glomerular filtration rate using chronic kidney disease epidemiology equations.
Subjects should be receiving moderate- or high-intensity statin therapy as defined by the American College of Cardiology/American Heart Association guideline on blood cholesterol management
Subjects should be on stable medication for a certain time period prior to randomization.
Provision of signed, written, and dated informed consent for mandatory and optional genetic research. All subjects in the study, except for healthy volunteers, need to consent to the mandatory genetic component of the study and sign the consent form for the main study.
If a healthy volunteer population is included by the SRC, then screen for eligibility criteria and study restrictions for healthy volunteer population.

Who cannot join

History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
Any uncontrolled or serious disease, or any medical (known major active infection or major hematological, renal, metabolic, gastrointestinal or endocrine dysfunction) or surgical condition that, in the opinion of the Investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk.
Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding (frequent bleeding gums or nose bleeds).
History of major bleed or high-risk of bleeding diathesis.
Subjects ≥ 20 years of age with a high 10-year risk of heart disease or stroke as calculated using the atherosclerotic cardiovascular disease (ASCVD) Risk Estimator.
Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in-situ, or Stage 1 prostate carcinoma) within the last 10 years.

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Recipient of any major organ transplant, eg, lung, liver, heart, bone marrow, renal.
LDL or plasma apheresis within 12 months prior to randomization.
Uncontrolled hypertension defined as supine SBP >160 mmHg or DBP >90 mmHg.
Heart rate after 10 minutes supine rest <50 or >100 bpm.
Any laboratory values with the following deviations at the Screening Visit or Day -1, test may be repeated at the discretion of the Investigator if abnormal: Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus; ALT > 1.5 times (Upper limit of normal [ULN]); AST >1.5 times ULN; Creatinine > 1.5 mg/dL; WBC < lower limit of normal (LLN); Hemoglobin < 12 g/dL in men or < 11 g/dL in women; Platelet count ≤ LLN; activated partial thromboplastin time > ULN and prothrombin time > ULN; urinary albumin-to-creatinine ratio > 11 mg/μmol.
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 (QTcF > 450 ms) changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy, test may be repeated at the discretion of the Investigator if abnormal.
Males who are unwilling to use an acceptable method of birth control during the entire study period. Acceptable methods of preventing pregnancy are true abstinence or use together, with their female partner/spouse, birth control pills, injections, implants, patches, or intrauterine devices in combination with a barrier method. A barrier method is not necessary if the female partner is sterilized.
Known or suspected history of drug abuse by the Investigator. 15, Smokers with > 10 cigarettes/day and unable to comply with the nicotine restriction during the study.
16. History of alcohol abuse or excessive intake of alcohol as judged by the Investigator.
17. Positive screen for drugs of abuse at the Screening Visit or admission to the study site.
18. Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate,) as judged by the Investigator.
19. Use of drugs with cytochrome 450 enzyme inducing properties such as St John's Wort within 3 weeks before the first administration of investigational medicinal product (IMP).
20. Insulin or glucagon-like peptide 1 receptor agonist therapy during last 3 months prior to randomization.
21. Anti-platelet therapy, other than low dose aspirin ≤ 100 mg/day, within 1 month prior to randomization.
22. Mipomersen, or lomitapide within 12 months prior to randomization. 23. Proprotein convertase subtilisin/kexin type 9 inhibition treatment within 6 months prior to randomization.
24. Use of any herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or 5 half-lives, whichever is longer.
25. Previous administration of AZD8233/AZD6615. 26. Received another new chemical entity within 30 days of last follow-up to first administration of the IMP of this study or 5 half-lives from last dose to first administration of IMP, whichever is the longest.
27. 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.
28. 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.
29. Involvement of any Astra Zeneca or study site employee or their close relatives.
30. Subjects who cannot communicate reliably with the Investigator. 31. Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
32. Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP. History or evidence of any other clinically significant disorder (eg, cognitive impairment), condition or disease other than those outlined above that, in the opinion of the Investigator or AstraZeneca physician, if consulted, may compromise the ability of the subject to give written informed consent, would pose a risk to subject safety, or interfere with the study evaluation, procedures or completion.
33. Subject likely to not be available to complete all protocol required study visits or procedures, to the best of the subject's and Investigator's knowledge.
34. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Research Site
Brooklyn, Maryland, 21225
Research Site
Chula Vista, California, 91911
Research Site
Glendale, California, 91206
Research Site
Jacksonville, Florida, 32216
Research Site
La Mesa, California, 91942
Research Site
Orlando, Florida, 32806
Research Site
Port Orange, Florida, 32127

Other trials in United States

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 Multiple Ascending Subcutaneous Dose Administration in Subjects With Dyslipidemia With or Without Type 2 Diabetes

Read the detailed description

This study is a Phase 1, randomized, single-blind, placebo-controlled, multiple dose group design in up to 33 male or female subjects with dyslipidemia with or without Type 2 diabetes and performed at multiple study centers. The planned number of cohorts is 3 but up to 5 cohorts may be included if the Safety Review Committee (SRC) considers it necessary. The 3 multiple dose levels of SC AZD8233 planned are:

Cohort 1: Dose 1 (starting dose).
Cohort 2: Dose 2 (provisional dose).
Cohort 3: Dose 3 (provisional dose). Within each of these cohorts, 8 subjects will be randomized to receive AZD8233 and 3 subjects randomized to receive placebo. Cohorts 2 and 3 may be run in parallel if Cohort 3 is a lower dose. If Cohort 3 is a higher dose, the cohorts will be run sequentially. At any time, the dose levels may be adapted by the SRC based on emerging data. The expected duration of each patient in this study is up to 28 weeks with a maximum of 17 visits. Screening will be completed between Days -28 and -1. Each subject will receive single doses of AZD8233 or placebo on Days 1, 8, 29, and 57. The treatment period will consist of 58 days (up to Visit 9), followed by a follow-up period (up to Visit 17).

Following review of data, the SRC may decide to adjust the following for subsequent cohorts:

The timing and amount of the loading dose.
The length of the stay at the study site, the timing and number of assessments and/or samples.
As decided by the SRC, blood and urine samples collected in the study may be used to address any of the other pre-specified study objectives.
Each subject will be followed up for 16 weeks post last dose.

Conditions: Dyslipidemia
Being tested: AZD8233 subcutaneous injection, Placebo
Keywords: Multiple Ascending Dose, AZD8233, Safety, Tolerability, PK, PD
Medical subject headings: Dyslipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD8233 subcutaneous injectionDrug
Randomized subjects will receive SC dose of AZD8233 (dose 1, dose 2, and dose 3) injection.
PlaceboDrug
Randomized subjects will receive SC dose of placebo injection.

Study groups in NCT04155645
Study group	Role	What they receive
Cohort 1	Experimental	On Days 1, 8, 29, and 57, randomized subjects will receive SC dose of AZD8233 dose 1 injection (8 subjects) or matching placebo (3 subjects). Receives: Drug: AZD8233 subcutaneous injection; Drug: Placebo
Cohort 2	Experimental	On Days 1, 8, 29, and 57, randomized subjects will receive SC dose of AZD8233 dose 2 injection (8 subjects) or matching placebo (3 subjects). Receives: Drug: AZD8233 subcutaneous injection; Drug: Placebo
Cohort 3	Experimental	On Days 1, 8, 29, and 57, randomized subjects will receive SC dose of AZD8233 dose 3 injection (8 subjects) or matching placebo (3 subjects). Receives: Drug: AZD8233 subcutaneous injection; Drug: Placebo

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 multiple ascending dose treatment.
To assess AEs as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses. Serious AEs will be recorded from the time of informed consent.
Measured: From randomization to final Follow-up Visit (Week 16 post last dose).
Vital sign: Systolic blood pressure (SBP)
To assess SBP as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses. BP will be collected after the subject has rested in the supine position for at least 5 minutes.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Vital sign: Pulse rate
To assess supine position pulse as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses. Pulse rate will be collected after the subject has rested in the supine position for at least 5 minutes.
Measured: From screening visit to final Follow-up Visit (Week 16 post last dose).
Vital sign: Oral body temperature
To assess the oral body temperature as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: Day -1 to final Follow-up Visit (Week 16 post last dose).
Number of patients with abnormal findings in resting 12-lead Electrocardiogram (ECG) and digital ECG (dECG).
To assess the 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 multiple ascending doses. ECG evaluations will be recorded after approximately 10 min resting in supine position. dECGs will be done only on Days 1 and 57 (pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24, 36 and 48 hours post-dose), and Days 8 and 29 (pre-dose).
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Number of subject with abnormal findings in cardiac telemetry
To assess cardiac telemetry as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: At Day -1, Days 1 to 3 (pre-dose to 24 hours post-dose), and Day 57 (pre-dose to 24 hours post-dose).
Physical examination
To assess physical examination as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses. Complete (general appearance, respiratory, cardiovascular, abdomen, skin, head and neck [including ears, eyes, nose and throat], lymph nodes, thyroid, musculoskeletal [including spine and extremities] and neurological systems).
Measured: From screening to final Follow-up Visit (Week 16 post last 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 multiple ascending doses.
Measured: From randomization to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Hematology - Blood cells count
To assess red blood cells (RBC) and white blood cells (WBC) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Hematology - Hemoglobin (Hb)
To assess Hb as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Hematology - Hematocrit (HCT)
To assess HCT as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Hematology - Mean corpuscular volume (MCV)
To assess MCV as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Hematology - Mean corpuscular hemoglobin (MCH)
To assess MCH as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Hematology - Mean corpuscular hemoglobin concentration (MCHC)
To assess MCHC as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Hematology - Differential WBC 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 multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Hematology - Platelet count and platelet function assessment.
To assess platelet count and platelet function in platelet rich plasma (PRP) using Light Transmission Aggregometry (LTA) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Hematology - Reticulocytes absolute count
To assess Reticulocytes absolute count as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Serum clinical chemistry - Electrolytes
To assess serum level of sodium, potassium, calcium as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Serum clinical chemistry - Blood urea nitrogen (BUN)
To assess serum level of BUN as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
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 multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
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 multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Serum clinical chemistry - Creatine kinase
To assess the level of serum creatine kinase as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Serum clinical chemistry - Direct bilirubin
To assess the level of serum bilirubin (direct) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Serum clinical chemistry - Hemoglobin A1c (HbA1c)
To assess the level of HbA1c as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Serum clinical chemistry - Liver enzymes
To assess the level 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 multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Serum clinical chemistry - Total bilirubin
To assess the level of serum bilirubin (total) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Serum clinical chemistry - Cell enzymes
To assess the level of serum glutamate dehydrogenase (GLDH) and lactate dehydrogenase (LDH) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Serum clinical chemistry - Bicarbonate
To assess the level of bicarbonate as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Serum clinical chemistry - Uric acid
To assess the level of uric acid as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Laboratory assessments: Coagulation
To assess activated partial thrombin time (aPTT), prothrombin time (PT), and International normalized ratio (INR) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Renal safety biomarkers - Urine clusterin
To assess renal biomarker by evaluation of urine clusterin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
Renal safety biomarkers - Urine cystatin-C
To assess renal biomarker by evaluation of urine cystatin-C level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
Renal safety biomarkers - Urine N-acetyl-beta-D-glucosaminidase (NAG)
To assess renal biomarker by evaluation of urine NAG level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
Renal safety biomarkers - Urine albumin
To assess renal biomarker by evaluation of urine albumin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
Renal safety biomarkers - Urine creatinine
To assess renal biomarker by evaluation of urine creatinine level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
Renal safety biomarkers - Urine Kidney injury molecule1 (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 multiple ascending doses.
Measured: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
Renal safety biomarkers - Urine Neutrophil gelatinase-associated lipocalin (NGAL)
To assess renal biomarker by evaluation of urine NAG level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
Renal safety biomarkers - Urine Osteopontin
To assess renal biomarker by evaluation of urine osteopontin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
Renal safety biomarkers - Urine total protein
To assess renal biomarker by evaluation of urine protein (total) level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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 multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).
Complement Activation panel
To assess chemotactic factor (C3a, Bb, and C5a) levels as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (pre-dose, 1, 2, and 4 hours post-dose).
Laboratory assessments: Clinical urinalysis
To assess urine sample for proteins, blood, creatinine, microscopy evaluation as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Measured: From screening to final Follow-up Visit (Week 16 post last dose).

Secondary outcomes (17)

Plasma PK analysis: Time delay between drug administration and the first observed concentration in plasma (tlag).
To characterize the tlag of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Time to reach peak or maximum observed concentration or response following drug administration (tmax).
To characterize the tmax of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Observed maximum plasma concentration (Cmax).
To characterize the Cmax of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Area under the plasma concentration-curve from time zero to time last value above the limit of quantification (AUC[0-last]).
To characterize the AUC(0-last) of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Area under the concentration-time curve from time zero to 24 hours post-dose (AUC[0-24]).
To characterize the AUC(0-24) of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Area under the concentration-time curve from time zero to 48 hours post-dose (AUC[0-48]).
To characterize the AUC(0-48) of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Area under the concentration-time curve from time zero extrapolated to infinity (AUC).
To characterize the AUC of AZD8233 following SC administration of multiple ascending doses. AUC is estimated by AUC(0-last) + Clast/λz where Clast is the last observed quantifiable concentration.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Area under the plasma concentration-time curve from time during the dosing interval (AUCt).
To characterize the AUCt of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Observed trough plasma drug concentration (Ctrough).
To characterize the Ctrough of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Apparent total body clearance of drug from plasma after extravascular administration (CL/F).
To characterize the CL/F of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Apparent volume of distribution for parent drug at terminal phase (extravascular administration) (Vz/F).
To characterize the Vz/F of AZD8233 following SC administration of multiple ascending doses; estimated by dividing the apparent clearance (CL/F) by λz.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Half-life associated with the terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2).
To characterize the t1/2 of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Mean Residence Time (MRT).
To characterize the MRT of AZD8233 following SC administration of multiple ascending doses.
Measured: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Urine PK analysis: Amount excreted in urine (Ae).
To characterize the Ae of AZD8233 following SC administration of multiple ascending doses.
Measured: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
Urine PK analysis: Fraction excreted unchanged in urine (Fe).
To characterize the Fe of AZD8233 following SC administration of multiple ascending doses.
Measured: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
Urine PK analysis: Renal clearance (CLR).
To characterize the CLR of AZD8233 following SC administration of multiple ascending doses.
Measured: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
PD analysis: Levels of dyslipidemia related biomarkers.
To assess the effect of AZD8233 on levels of dyslipidemia related biomarkers.
Measured: At screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8 (pre-dose), Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Nov 20197 Jun 2021

First posted7 Nov 2019
Study start21 Nov 2019
Primary completion7 Jun 2021
Study completion7 Jun 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for DyslipidemiaStudies 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: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04155645
Sponsor's protocol ID: D7990C00002
Status last verified: Jun 2021
First submitted: 5 Nov 2019
Last updated: 30 Jun 2021
Results posted: No
Data monitoring committee: Yes
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.

Publications

Clewe O, Rekic D, Quartino AL, Carlsson B, Higashimori M, Wernevik L, Hofherr A, Ryden-Bergsten T, Nilsson C, Knochel J. Population pharmacokinetics of a novel PCSK9 antisense oligonucleotide. Br J Clin Pharmacol. 2024 Jun;90(6):1503-1513. doi: 10.1111/bcp.16046. Epub 2024 Mar 19.
PubMed 38504437

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Not yet recruiting
Plasma Lipids-Dependent Vitamin E Metabolism During Dynamic Hyperlipidemia
Lipid Metabolism Disorders
Active, not recruitingObservational study
A Longitudinal Cohort Study to Evaluate Cardiovascular Risk Factors and Disease in Haiti
Hypertension, Diabetes
Active, not recruiting
Developing a Learning COmmunity to Increase eNgagemeNt and Enrollment in Cardiovascular Clinical Trials (CONNECT)
Cardiovascular Diseases, Hypertension
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease

All Dyslipidemia trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Jun 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 Multiple Ascending Subcutaneous Dose Administration in Subjects With Dyslipidemia With or Without Type 2 Diabetes
ClinicalTrials.gov ID: NCT04155645
Acronym / sponsor ID: D7990C00002
Conditions: Dyslipidemia
Keywords: Multiple Ascending Dose, AZD8233, Safety, Tolerability, PK, PD
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Parexel
Study start: 21 Nov 2019 (actual)
Primary completion: 7 Jun 2021 (actual)
Study completion: 7 Jun 2021 (actual)
First posted: 7 Nov 2019 (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.

Detailed description

Cohort 1: Dose 1 (starting dose).
Cohort 2: Dose 2 (provisional dose).
Cohort 3: Dose 3 (provisional dose). Within each of these cohorts, 8 subjects will be randomized to receive AZD8233 and 3 subjects randomized to receive placebo. Cohorts 2 and 3 may be run in parallel if Cohort 3 is a lower dose. If Cohort 3 is a higher dose, the cohorts will be run sequentially. At any time, the dose levels may be adapted by the SRC based on emerging data. The expected duration of each patient in this study is up to 28 weeks with a maximum of 17 visits. Screening will be completed between Days -28 and -1. Each subject will receive single doses of AZD8233 or placebo on Days 1, 8, 29, and 57. The treatment period will consist of 58 days (up to Visit 9), followed by a follow-up period (up to Visit 17).

Following review of data, the SRC may decide to adjust the following for subsequent cohorts:

The timing and amount of the loading dose.
The length of the stay at the study site, the timing and number of assessments and/or samples.
As decided by the SRC, blood and urine samples collected in the study may be used to address any of the other pre-specified study objectives.
Each subject will be followed up for 16 weeks post last dose.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 3

Arm	Type	Receives
Cohort 1	Experimental	Drug: AZD8233 subcutaneous injection, Drug: PlaceboOn Days 1, 8, 29, and 57, randomized subjects will receive SC dose of AZD8233 dose 1 injection (8 subjects) or matching placebo (3 subjects).
Cohort 2	Experimental	Drug: AZD8233 subcutaneous injection, Drug: PlaceboOn Days 1, 8, 29, and 57, randomized subjects will receive SC dose of AZD8233 dose 2 injection (8 subjects) or matching placebo (3 subjects).
Cohort 3	Experimental	Drug: AZD8233 subcutaneous injection, Drug: PlaceboOn Days 1, 8, 29, and 57, randomized subjects will receive SC dose of AZD8233 dose 3 injection (8 subjects) or matching placebo (3 subjects).

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Provision of signed and dated, written informed consent before any study specific procedures.
Must be willing and able to comply with all required study procedures.
Male or female subjects aged 18 to 65 years at signing of informed consent.
Females must not be pregnant and must have a negative urine pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating; or must be of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria:
Have suitable veins for cannulation or repeated venipuncture.

Key exclusion criteria (30 listed)

History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
Any uncontrolled or serious disease, or any medical (known major active infection or major hematological, renal, metabolic, gastrointestinal or endocrine dysfunction) or surgical condition that, in the opinion of the Investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk.
Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding (frequent bleeding gums or nose bleeds).
History of major bleed or high-risk of bleeding diathesis.
Subjects ≥ 20 years of age with a high 10-year risk of heart disease or stroke as calculated using the atherosclerotic cardiovascular disease (ASCVD) Risk Estimator.

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
AZD8233 subcutaneous injectionRandomized subjects will receive SC dose of AZD8233 (dose 1, dose 2, and dose 3) injection.	Drug	Cohort 1, Cohort 2, Cohort 3
PlaceboRandomized subjects will receive SC dose of placebo injection.	Drug	Cohort 1, Cohort 2, Cohort 3

Primary outcome

Number of subjects with adverse events (AEs) due to AZD8233 SC multiple ascending dose treatment.
Time frame: From randomization to final Follow-up Visit (Week 16 post last dose).
To assess AEs as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses. Serious AEs will be recorded from the time of informed consent.
Vital sign: Systolic blood pressure (SBP)
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess SBP as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses. BP will be collected after the subject has rested in the supine position for at least 5 minutes.
Vital sign: Pulse rate
Time frame: From screening visit to final Follow-up Visit (Week 16 post last dose).
To assess supine position pulse as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses. Pulse rate will be collected after the subject has rested in the supine position for at least 5 minutes.
Vital sign: Oral body temperature
Time frame: Day -1 to final Follow-up Visit (Week 16 post last dose).
To assess the oral body temperature as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Number of patients with abnormal findings in resting 12-lead Electrocardiogram (ECG) and digital ECG (dECG).
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess the 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 multiple ascending doses. ECG evaluations will be recorded after approximately 10 min resting in supine position. dECGs will be done only on Days 1 and 57 (pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24, 36 and 48 hours post-dose), and Days 8 and 29 (pre-dose).
Number of subject with abnormal findings in cardiac telemetry
Time frame: At Day -1, Days 1 to 3 (pre-dose to 24 hours post-dose), and Day 57 (pre-dose to 24 hours post-dose).
To assess cardiac telemetry as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Physical examination
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess physical examination as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses. Complete (general appearance, respiratory, cardiovascular, abdomen, skin, head and neck [including ears, eyes, nose and throat], lymph nodes, thyroid, musculoskeletal [including spine and extremities] and neurological systems).
Injection site reaction examinations
Time frame: From randomization to final Follow-up Visit (Week 16 post last dose).
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 multiple ascending doses.
Laboratory assessments: Hematology - Blood cells count
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess red blood cells (RBC) and white blood cells (WBC) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Hematology - Hemoglobin (Hb)
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess Hb as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Hematology - Hematocrit (HCT)
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess HCT as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Hematology - Mean corpuscular volume (MCV)
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess MCV as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Hematology - Mean corpuscular hemoglobin (MCH)
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess MCH as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Hematology - Mean corpuscular hemoglobin concentration (MCHC)
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess MCHC as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Hematology - Differential WBC count
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
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 multiple ascending doses.
Laboratory assessments: Hematology - Platelet count and platelet function assessment.
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess platelet count and platelet function in platelet rich plasma (PRP) using Light Transmission Aggregometry (LTA) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Hematology - Reticulocytes absolute count
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess Reticulocytes absolute count as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Electrolytes
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess serum level of sodium, potassium, calcium as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Blood urea nitrogen (BUN)
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess serum level of BUN as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Creatinine
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess serum level of creatinine as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Glucose (fasting)
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess serum fasting glucose level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Creatine kinase
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess the level of serum creatine kinase as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Direct bilirubin
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess the level of serum bilirubin (direct) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Hemoglobin A1c (HbA1c)
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess the level of HbA1c as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Liver enzymes
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess the level 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 multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Total bilirubin
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess the level of serum bilirubin (total) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Cell enzymes
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess the level of serum glutamate dehydrogenase (GLDH) and lactate dehydrogenase (LDH) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Bicarbonate
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess the level of bicarbonate as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Serum clinical chemistry - Uric acid
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess the level of uric acid as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Coagulation
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess activated partial thrombin time (aPTT), prothrombin time (PT), and International normalized ratio (INR) as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Renal safety biomarkers - Urine clusterin
Time frame: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
To assess renal biomarker by evaluation of urine clusterin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Renal safety biomarkers - Urine cystatin-C
Time frame: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
To assess renal biomarker by evaluation of urine cystatin-C level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Renal safety biomarkers - Urine N-acetyl-beta-D-glucosaminidase (NAG)
Time frame: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
To assess renal biomarker by evaluation of urine NAG level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Renal safety biomarkers - Urine albumin
Time frame: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
To assess renal biomarker by evaluation of urine albumin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Renal safety biomarkers - Urine creatinine
Time frame: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
To assess renal biomarker by evaluation of urine creatinine level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Renal safety biomarkers - Urine Kidney injury molecule1 (KIM-1)
Time frame: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
To assess renal biomarker by evaluation of urine KIM-1 level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Renal safety biomarkers - Urine Neutrophil gelatinase-associated lipocalin (NGAL)
Time frame: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
To assess renal biomarker by evaluation of urine NAG level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Renal safety biomarkers - Urine Osteopontin
Time frame: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
To assess renal biomarker by evaluation of urine osteopontin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Renal safety biomarkers - Urine total protein
Time frame: Screening, Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
To assess renal biomarker by evaluation of urine protein (total) level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Immune Activation Response - High-sensitivity C-reactive protein (hs-CRP)
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess hs-CRP level as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Complement Activation panel
Time frame: Days 1 and 57 (pre-dose, 1, 2, and 4 hours post-dose).
To assess chemotactic factor (C3a, Bb, and C5a) levels as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Laboratory assessments: Clinical urinalysis
Time frame: From screening to final Follow-up Visit (Week 16 post last dose).
To assess urine sample for proteins, blood, creatinine, microscopy evaluation as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.

17 secondary outcomes

Plasma PK analysis: Time delay between drug administration and the first observed concentration in plasma (tlag).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Time to reach peak or maximum observed concentration or response following drug administration (tmax).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Observed maximum plasma concentration (Cmax).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Area under the plasma concentration-curve from time zero to time last value above the limit of quantification (AUC[0-last]).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Area under the concentration-time curve from time zero to 24 hours post-dose (AUC[0-24]).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Area under the concentration-time curve from time zero to 48 hours post-dose (AUC[0-48]).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Area under the concentration-time curve from time zero extrapolated to infinity (AUC).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Area under the plasma concentration-time curve from time during the dosing interval (AUCt).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Observed trough plasma drug concentration (Ctrough).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Apparent total body clearance of drug from plasma after extravascular administration (CL/F).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Apparent volume of distribution for parent drug at terminal phase (extravascular administration) (Vz/F).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Half-life associated with the terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Plasma PK analysis: Mean Residence Time (MRT).
Time frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
Urine PK analysis: Amount excreted in urine (Ae).
Time frame: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
Urine PK analysis: Fraction excreted unchanged in urine (Fe).
Time frame: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
Urine PK analysis: Renal clearance (CLR).
Time frame: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
PD analysis: Levels of dyslipidemia related biomarkers.
Time frame: At screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8 (pre-dose), Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.

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 30 Jun 2021.
Derived from this study: PubMed 38504437Clewe O, Rekic D, Quartino AL, Carlsson B, Higashimori M, Wernevik L, Hofherr A, Ryden-Bergsten T, Nilsson C, Knochel J. Population pharmacokinetics of a novel PCSK9 antisense oligonucleotide. Br J Clin Pharmacol. 2024 Jun;90(6):1503-1513. doi: 10.1111/bcp.16046. Epub 2024 Mar 19.
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, MD principal investigator

PAREXEL Early Phase Clinical Unit-Los Angeles

7 sites 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 subcutaneous injection in people with Dyslipidemia, run by AstraZeneca at 7 sites 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 14 inclusion and 30 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 30 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites 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 multiple ascending dose treatment. (time frame: From randomization to final Follow-up Visit (Week 16 post last dose).). The study lists 42 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04155645, which also lists 1 linked publication.

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 30 Jun 2021.