Dyslipidaemia
Conditions
Keywords
Dose Range Finding, AZD8233, Efficacy, PK, PD, Immunogenicity, Safety, Tolerability
Brief summary
AZD8233 is a PCSK9-targeted ASO for the reduction of circulating levels of LDL-C. This study aims to evaluate the dose-dependent reduction in LDL-C after SC administration of multiple doses of AZD8233 as well as the associated adverse effects profile. The data generated will be used to guide choice of doses, dosing regimens, and sample sizes, as well as safety and PD monitoring in the further clinical development program.
Detailed description
This is a randomized parallel, double-blind, placebo-controlled, dose-ranging Phase 2b study in approximately 108 participants with dyslipidemia. The primary objective of the study is to investigate the effect of AZD8233 on LDL-C across different dose levels. The study will be conducted at up to 25 sites in up to 4 countries. The screening period starts up to 42 days before the randomization visit and ends on Day -1. Eligible participants will attend 7 visits during the treatment period and 7 additional visits during the safety follow up period. Eligible participants are randomized across four different treatment arms in a 1:1:1:1 ratio for a 12-week treatment period. The planned treatment arms are AZD8233 low dose, AZD8233 medium dose, AZD8233 high dose, and Placebo. Participants will be dosed SC on Days 1, 8, 29, and 57.
Interventions
DRUGAZD8233
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
DRUGPlacebo
Placebo solution
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or female. * Participant must be 18 to 75 years of age. * Body mass index between 19 and 40 kg/m2. * Participants who have a fasting LDL-C ≥ 70 mg/dL but \< 190 mg/dL. * Have fasting triglycerides \< 400 mg/dL. * Should be receiving moderate- or high-intensity statin therapy. * Should be on stable medication for ≥ 3 months prior to screening with no planned medication or dose change during study participation. The exception to this restriction is for fenofibrate; if the participant is receiving fenofibrate, the therapy must be stable for at least 6 weeks prior to randomization at a dose that is appropriate for the duration of the study in the judgement of the Investigator. Other fibrate therapy (and derivatives) are prohibited. Key
Exclusion criteria
* Estimated glomerular filtration rate \< 40 mL/min/1.73m2 CKD-EPI. * Any uncontrolled or serious disease, or any medical 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. * Poorly controlled type 2 diabetes mellitus, defined as HbA1c \> 10% at Visit 1. * Acute ischaemic cardiovascular event in the last 12 months prior to randomization. * Heart failure with New York Heart Association (NYHA) Class III-IV. * High-risk of bleeding as judged by the Investigator. * 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. * LDL or plasma apheresis within 12 months prior to randomization. * Uncontrolled hypertension defined as average supine SBP \> 160 mmHg or DBP \> 90 mmHg at Visit 1 or Visit 3. * Heart rate after 10 minutes supine rest \< 50 bpm or \> 100 bpm. * Any laboratory values with the following deviations at Screening: * Positive result on screening for hepatitis B, hepatitis C or HIV. * ALT \> 1.5 × ULN. * AST \> 1.5 × ULN. * TBL \> ULN. * ALP \> 1.5 × ULN. * WBC \< LLN. * Haemoglobin \< 12 g/dL in men or \< 11 g/dL in women. * Platelet count ≤ LLN. * aPTT \> ULN and PT \> ULN. * UACR \> 11.3 mg/mmol (100 mg/g). * UPCR \> 300 mg/g. * Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG as judged by the Investigator. * Mipomersen, or lomitapide within 12 months prior to randomization. * Previous administration of AZD8233/AZD6615. * Previous administration of PCSK9 inhibition treatment. * Participation in another clinical study with a study intervention administered in the last 3 months prior to randomization or 5 half-lives from last dose to first administration of study intervention, whichever is the longest.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12. | Baseline to week 12 | Change from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12. | Baseline to week 12 | Relative change from baseline in PCSK9 concentration in plasma at week 12. |
| Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Baseline to week 12 | Percentage change from baseline in concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol at week 12 |
| Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Measurement at week 0, week 1, week 4, week 8, week 12, week 16, week 20, week 24 | ADA titre results for subjects with positive ADA during the treatment period and follow-up period. |
| Percentage Change From Baseline in Levels of LDL-C in Plasma | Baseline to week 12 | Percentage change from baseline in levels of LDL-C in plasma from baseline to week 12. |
| Plasma Concentration of AZD8233 | Measurement at week 1, week 4, week 6, week 8, week 10, week 12, week 16, week 20, week 24 after first dose administration. | Plasma concentration of AZD8233 after first dose administration |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant | Baseline to Week 24 | Number of subjects with an ECG determined to be abnormal and clinically significant at baseline and end of treatment. |
Countries
Denmark, Slovakia, United States
Participant flow
Recruitment details
This study was conducted at 19 clinical research center in Denmark, Slovakia and the USA. First subject enrolled (First subject first visit/first consent signed date): 28 October 2020. Last subject last visit: 20 July 2021.
Participants by arm
| Arm | Count |
|---|---|
| AZD8233 High Dose AZD8233 high dose for subcutaneous injection. | 29 |
| AZD8233 Medium Dose AZD8233 medium dose for subcutaneous injection. | 30 |
| AZD8233 Low Dose AZD8233 low dose for subcutaneous injection. | 30 |
| Placebo Placebo solution for subcutaneous injection. | 30 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Reason not given | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | AZD8233 High Dose | AZD8233 Medium Dose | AZD8233 Low Dose | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60.4 Years STANDARD_DEVIATION 8.4 | 60.6 Years STANDARD_DEVIATION 7.4 | 61.8 Years STANDARD_DEVIATION 7.1 | 63.9 Years STANDARD_DEVIATION 7.3 | 61.7 Years STANDARD_DEVIATION 7.6 |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized ASIAN | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized WHITE | 28 Participants | 28 Participants | 27 Participants | 27 Participants | 110 Participants |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 16 Participants | 18 Participants | 57 Participants |
| Sex: Female, Male Male | 18 Participants | 18 Participants | 14 Participants | 12 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 20 / 29 | 17 / 30 | 14 / 30 | 12 / 30 |
| serious Total, serious adverse events | 1 / 29 | 2 / 30 | 1 / 30 | 0 / 30 |
Outcome results
Primary
Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12.
Change from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed.
Time frame: Baseline to week 12
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12. | 0.978 Ratio |
| AZD8233 High Dose | Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12. | 0.206 Ratio |
| AZD8233 Medium Dose | Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12. | 0.270 Ratio |
| AZD8233 Low Dose | Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12. | 0.606 Ratio |
Secondary
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period
ADA titre results for subjects with positive ADA during the treatment period and follow-up period.
Time frame: Measurement at week 0, week 1, week 4, week 8, week 12, week 16, week 20, week 24
Population: Number Analyzed per Row reflects the study participants with positive ADA results at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 12 | 50 ADA titre |
| Placebo | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 8 | 100 ADA titre |
| Placebo | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 20 | 100 ADA titre |
| Placebo | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 1 | 100 ADA titre |
| Placebo | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 16 | 100 ADA titre |
| Placebo | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Baseline | 100 ADA titre |
| Placebo | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 4 | 100 ADA titre |
| Placebo | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 24 | 100 ADA titre |
| AZD8233 High Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 12 | 200 ADA titre |
| AZD8233 High Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 4 | 75 ADA titre |
| AZD8233 High Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 8 | 75 ADA titre |
| AZD8233 High Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 16 | 300 ADA titre |
| AZD8233 High Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 20 | 500 ADA titre |
| AZD8233 High Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 24 | 200 ADA titre |
| AZD8233 Medium Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 12 | 200 ADA titre |
| AZD8233 Medium Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 24 | 300 ADA titre |
| AZD8233 Medium Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 20 | 200 ADA titre |
| AZD8233 Medium Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 16 | 200 ADA titre |
| AZD8233 Medium Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 1 | 200 ADA titre |
| AZD8233 Medium Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Baseline | 200 ADA titre |
| AZD8233 Medium Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 8 | 200 ADA titre |
| AZD8233 Medium Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 4 | 200 ADA titre |
| AZD8233 Low Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 8 | 400 ADA titre |
| AZD8233 Low Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 1 | 100 ADA titre |
| AZD8233 Low Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 12 | 200 ADA titre |
| AZD8233 Low Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 24 | 400 ADA titre |
| AZD8233 Low Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 16 | 400 ADA titre |
| AZD8233 Low Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Baseline | 100 ADA titre |
| AZD8233 Low Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 20 | 400 ADA titre |
| AZD8233 Low Dose | Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period | Week 4 | 150 ADA titre |
Secondary
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol
Percentage change from baseline in concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol at week 12
Time frame: Baseline to week 12
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Lp(a) | 31.22 Percent |
| Placebo | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Remnants cholesterol | 6.38 Percent |
| Placebo | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | HDL-C | 1.34 Percent |
| Placebo | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Non-HDL-C | -0.65 Percent |
| Placebo | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Triglycerides | 2.69 Percent |
| Placebo | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | VLDL-C | 3.22 Percent |
| Placebo | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | ApoB | -1.65 Percent |
| Placebo | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Total cholesterol | -1.11 Percent |
| AZD8233 High Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | VLDL-C | -11.13 Percent |
| AZD8233 High Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Lp(a) | -37.74 Percent |
| AZD8233 High Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Non-HDL-C | -67.92 Percent |
| AZD8233 High Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Total cholesterol | -47.58 Percent |
| AZD8233 High Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | ApoB | -67.07 Percent |
| AZD8233 High Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Remnants cholesterol | -26.84 Percent |
| AZD8233 High Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | HDL-C | 5.57 Percent |
| AZD8233 High Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Triglycerides | -12.70 Percent |
| AZD8233 Medium Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Total cholesterol | -43.90 Percent |
| AZD8233 Medium Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | HDL-C | 6.50 Percent |
| AZD8233 Medium Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Triglycerides | -12.95 Percent |
| AZD8233 Medium Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | VLDL-C | -12.09 Percent |
| AZD8233 Medium Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Non-HDL-C | -61.25 Percent |
| AZD8233 Medium Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | ApoB | -60.13 Percent |
| AZD8233 Medium Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Lp(a) | -36.64 Percent |
| AZD8233 Medium Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Remnants cholesterol | -16.54 Percent |
| AZD8233 Low Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Remnants cholesterol | -13.50 Percent |
| AZD8233 Low Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Triglycerides | -7.70 Percent |
| AZD8233 Low Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Total cholesterol | -21.13 Percent |
| AZD8233 Low Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | HDL-C | 3.37 Percent |
| AZD8233 Low Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Non-HDL-C | -29.57 Percent |
| AZD8233 Low Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | ApoB | -29.50 Percent |
| AZD8233 Low Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | Lp(a) | -6.02 Percent |
| AZD8233 Low Dose | Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol | VLDL-C | -7.54 Percent |
Secondary
Percentage Change From Baseline in Levels of LDL-C in Plasma
Percentage change from baseline in levels of LDL-C in plasma from baseline to week 12.
Time frame: Baseline to week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percentage Change From Baseline in Levels of LDL-C in Plasma | -1.53 Percent |
| AZD8233 High Dose | Percentage Change From Baseline in Levels of LDL-C in Plasma | -76.50 Percent |
| AZD8233 Medium Dose | Percentage Change From Baseline in Levels of LDL-C in Plasma | -69.26 Percent |
| AZD8233 Low Dose | Percentage Change From Baseline in Levels of LDL-C in Plasma | -32.22 Percent |
Secondary
Plasma Concentration of AZD8233
Plasma concentration of AZD8233 after first dose administration
Time frame: Measurement at week 1, week 4, week 6, week 8, week 10, week 12, week 16, week 20, week 24 after first dose administration.
Population: No analysis made for placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of AZD8233 | Week 16 | 0.507 ug/L | Standard Deviation 0.7 |
| Placebo | Plasma Concentration of AZD8233 | Week 6 | 1.917 ug/L | Standard Deviation 1.09 |
| Placebo | Plasma Concentration of AZD8233 | Week 20 | 0.376 ug/L | Standard Deviation 0.68 |
| Placebo | Plasma Concentration of AZD8233 | Week 24 | 0.350 ug/L | Standard Deviation 0.62 |
| Placebo | Plasma Concentration of AZD8233 | Week 8 | 1.000 ug/L | Standard Deviation 0.68 |
| Placebo | Plasma Concentration of AZD8233 | Week 1 | 1.201 ug/L | Standard Deviation 0.49 |
| Placebo | Plasma Concentration of AZD8233 | Week 10 | 1.562 ug/L | Standard Deviation 0.84 |
| Placebo | Plasma Concentration of AZD8233 | Week 4 | 1.366 ug/L | Standard Deviation 0.71 |
| Placebo | Plasma Concentration of AZD8233 | Week 12 | 0.976 ug/L | Standard Deviation 0.75 |
| AZD8233 High Dose | Plasma Concentration of AZD8233 | Week 10 | 0.751 ug/L | Standard Deviation 0.29 |
| AZD8233 High Dose | Plasma Concentration of AZD8233 | Week 16 | 0.297 ug/L | Standard Deviation 0.53 |
| AZD8233 High Dose | Plasma Concentration of AZD8233 | Week 8 | 0.628 ug/L | Standard Deviation 0.57 |
| AZD8233 High Dose | Plasma Concentration of AZD8233 | Week 12 | 0.476 ug/L | Standard Deviation 0.23 |
| AZD8233 High Dose | Plasma Concentration of AZD8233 | Week 20 | 0.153 ug/L | Standard Deviation 0.26 |
| AZD8233 High Dose | Plasma Concentration of AZD8233 | Week 6 | 0.870 ug/L | Standard Deviation 0.34 |
| AZD8233 High Dose | Plasma Concentration of AZD8233 | Week 4 | 0.699 ug/L | Standard Deviation 0.33 |
| AZD8233 High Dose | Plasma Concentration of AZD8233 | Week 24 | 0.111 ug/L | Standard Deviation 0.15 |
| AZD8233 High Dose | Plasma Concentration of AZD8233 | Week 1 | 0.681 ug/L | Standard Deviation 0.24 |
| AZD8233 Medium Dose | Plasma Concentration of AZD8233 | Week 24 | 0.111 ug/L | Standard Deviation 0.31 |
| AZD8233 Medium Dose | Plasma Concentration of AZD8233 | Week 1 | 0.346 ug/L | Standard Deviation 0.59 |
| AZD8233 Medium Dose | Plasma Concentration of AZD8233 | Week 6 | 0.288 ug/L | Standard Deviation 0.21 |
| AZD8233 Medium Dose | Plasma Concentration of AZD8233 | Week 8 | 0.152 ug/L | Standard Deviation 0.1 |
| AZD8233 Medium Dose | Plasma Concentration of AZD8233 | Week 10 | 0.241 ug/L | Standard Deviation 0.15 |
| AZD8233 Medium Dose | Plasma Concentration of AZD8233 | Week 12 | 0.134 ug/L | Standard Deviation 0.07 |
| AZD8233 Medium Dose | Plasma Concentration of AZD8233 | Week 16 | 0.087 ug/L | Standard Deviation 0.09 |
| AZD8233 Medium Dose | Plasma Concentration of AZD8233 | Week 20 | 0.053 ug/L | Standard Deviation 0.004 |
| AZD8233 Medium Dose | Plasma Concentration of AZD8233 | Week 4 | 0.238 ug/L | Standard Deviation 0.21 |
Secondary
Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12.
Relative change from baseline in PCSK9 concentration in plasma at week 12.
Time frame: Baseline to week 12
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12. | 0.950 Ratio |
| AZD8233 High Dose | Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12. | 0.060 Ratio |
| AZD8233 Medium Dose | Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12. | 0.110 Ratio |
| AZD8233 Low Dose | Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12. | 0.420 Ratio |
Other Pre-specified
Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant
Number of subjects with an ECG determined to be abnormal and clinically significant at baseline and end of treatment.
Time frame: Baseline to Week 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant | Baseline | 0 Number of subjects |
| Placebo | Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant | End of treatment | 0 Number of subjects |
| AZD8233 High Dose | Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant | End of treatment | 0 Number of subjects |
| AZD8233 High Dose | Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant | Baseline | 0 Number of subjects |
| AZD8233 Medium Dose | Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant | Baseline | 0 Number of subjects |
| AZD8233 Medium Dose | Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant | End of treatment | 0 Number of subjects |
| AZD8233 Low Dose | Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant | Baseline | 0 Number of subjects |
| AZD8233 Low Dose | Number of Subjects With an ECG Determined to be Abnormal and Clinically Significant | End of treatment | 0 Number of subjects |