Dyslipidemia
Conditions
Keywords
Dyslipidemia,, Low-Density Lipoprotein Cholesterol
Brief summary
The primary purpose of this study is to measure the effect of different daily doses of AZD0780 on Low-Density Lipoprotein (LDL-C) levels compared with placebo in participants with dyslipidemia. The effect of AZD0780 versus placebo on other lipid parameters and inflammatory markers is also investigated. The concentration of AZD0780 in blood at specific timepoints is measured, and the safety and tolerability of AZD0780 will be evaluated. There is a follow-up after end of treatment, but expanded access is not available. The primary hypothesis is that at least one of the investigated doses of AZD0780 is superior to placebo in lowering LDL-C level, in percent change from baseline up to week 12.
Interventions
DRUGAZD0780
AZD0780 administered orally, once daily for 12 weeks
DRUGPlacebo
Placebo administered orally, once daily for 12 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants will be randomized with equal distribution across 5 parallel treatment arms to either placebo or one of four AZD0780 doses.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Males, and females of non-childbearing potential 18 to 75 years of age, inclusive, at the time of signing the informed consent. * Participants with a fasting low-density lipoprotein cholesterol (LDL-C) higher than or equal to 70 mg/dL (1.8 mmol/L) and lower than 190 mg/dL (4.9 mmol/L) at screening. * Participants with fasting triglycerides lower than 400 mg/dL (lower than 4.52 mmol/L) at screening. * Should be receiving moderate or high-intensity statin therapy for more than or equal to 2 months prior to screening. * There should be no planned medication or dose change during study participation. * Body mass index at or above 19.0 kg/m\^2.
Exclusion criteria
* History or presence of gastrointestinal, hepatic or renal disease or any other conditions known to interfere with absorption, distribution, metabolism, or excretion of drugs. * Any uncontrolled or serious disease, or any medical (e.g., known major active infection or major hematological, renal, metabolic, gastrointestinal, respiratory, 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. * Poorly controlled type 2 diabetes mellitus, defined as hemoglobin A1c (HbA1c) greater than 10 percent at screening. * Acute ischemic cardiovascular event in the last 12 months. * Heart failure with New York Heart Association (NYHA) Class III-IV. * 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. * Recipient of any major organ transplant, e.g., lung, liver, heart, bone marrow, renal. * LDL or plasma apheresis within 12 months prior to randomization. * Uncontrolled hypertension. * Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level From Baseline to Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 LDL-C - Baseline LDL-C) / Baseline LDL-C \* 100. Negative values indicate reduction in LDL-C. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline of Total Cholesterol at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded. |
| Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded. |
| Percent Change From Baseline of Triglycerides at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded. |
| Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded. |
| Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded. |
| Percent Change From Baseline of Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 LDL-C - Baseline LDL-C) / Baseline LDL-C \* 100. Negative values indicate reduction in LDL-C. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained. |
| Percent Change From Baseline of Apolipoprotein B at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded. |
| Percent Change From Baseline of Lipoprotein-a at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Descriptive statistics only. |
| Percent Change From Baseline of Remnant Cholesterol at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Descriptive statistics only. |
| Percent Change From Baseline of High Sensitivity C-reactive Protein (hsCRP) at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Descriptive statistics only. |
| AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | From week 1 up to week 12 | Geometric mean plasma concentration; LLOQ = 0.01 umol/L; BLQ values are handled as Not Quantified (NQ) |
| Percent Change From Baseline of Apolipoprotein A1 at Week 12 | From first day of treatment up to week 12 | Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded. |
Countries
Canada, Czechia, Denmark, Hungary, Japan, Slovakia, Spain, United States
Participant flow
Recruitment details
The study was conducted from January 2024 to September 2024 in 55 research sites in 8 countries (United States, Canada, Czech Republic, Denmark, Hungary, Japan, Slovakia, and Spain).
Pre-assignment details
Of 428 enrolled participants, two randomized participants - one screen failure and one withdrawal by subject - did not start treatment.
Participants by arm
| Arm | Count |
|---|---|
| AZD0780 1 mg Participants received 1 mg of AZD0780 administered orally once daily for up to 12 weeks | 86 |
| AZD0780 3 mg Participants received 3 mg of AZD0780 administered orally once daily for up to 12 weeks | 85 |
| AZD0780 10 mg Participants received 10 mg of AZD0780 administered orally once daily for up to 12 weeks | 84 |
| AZD0780 30 mg Participants received 30 mg of AZD0780 administered orally once daily for up to 12 weeks | 85 |
| Placebo Participants received placebo administered orally once daily for up to 12 weeks | 86 |
| Total | 426 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 2 |
| Overall Study | Non-compliance with Study Drug | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 2 | 1 | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 2 | 0 | 0 | 1 |
| Overall Study | Screen Failure | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | AZD0780 1 mg | AZD0780 3 mg | AZD0780 10 mg | AZD0780 30 mg | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 39 Participants | 26 Participants | 45 Participants | 35 Participants | 39 Participants | 184 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants | 59 Participants | 39 Participants | 50 Participants | 47 Participants | 242 Participants |
| Age, Continuous | 62.7 Years STANDARD_DEVIATION 7.9 | 60.9 Years STANDARD_DEVIATION 7.2 | 63.9 Years STANDARD_DEVIATION 7.2 | 62.3 Years STANDARD_DEVIATION 7.9 | 62.3 Years STANDARD_DEVIATION 7.8 | 62.4 Years STANDARD_DEVIATION 7.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 10 Participants | 6 Participants | 12 Participants | 8 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 81 Participants | 75 Participants | 78 Participants | 73 Participants | 78 Participants | 385 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Low-Density Lipoprotein Cholesterol (LDL-C) | 2.6822 mmol/L STANDARD_DEVIATION 0.6918 | 2.7258 mmol/L STANDARD_DEVIATION 0.896 | 2.4784 mmol/L STANDARD_DEVIATION 0.7122 | 2.5500 mmol/L STANDARD_DEVIATION 0.6939 | 2.5769 mmol/L STANDARD_DEVIATION 0.662 | 2.6031 mmol/L STANDARD_DEVIATION 0.7378 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 32 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 4 Participants | 4 Participants | 6 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 73 Participants | 75 Participants | 73 Participants | 74 Participants | 73 Participants | 368 Participants |
| Sex: Female, Male Female | 41 Participants | 41 Participants | 37 Participants | 41 Participants | 44 Participants | 204 Participants |
| Sex: Female, Male Male | 45 Participants | 44 Participants | 47 Participants | 44 Participants | 42 Participants | 222 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 86 | 0 / 85 | 0 / 84 | 0 / 85 | 0 / 86 |
| other Total, other adverse events | 4 / 86 | 2 / 85 | 2 / 84 | 3 / 85 | 5 / 86 |
| serious Total, serious adverse events | 2 / 86 | 2 / 85 | 2 / 84 | 1 / 85 | 0 / 86 |
Outcome results
Primary
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level From Baseline to Week 12
Percent change was calculated as (Week 12 LDL-C - Baseline LDL-C) / Baseline LDL-C \* 100. Negative values indicate reduction in LDL-C. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level From Baseline to Week 12 | -31.19 Percent Change (%) |
| AZD0780 3 mg | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level From Baseline to Week 12 | -33.83 Percent Change (%) |
| AZD0780 10 mg | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level From Baseline to Week 12 | -41.09 Percent Change (%) |
| AZD0780 30 mg | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level From Baseline to Week 12 | -46.62 Percent Change (%) |
| Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level From Baseline to Week 12 | 4.08 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline LDL-C, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 LDL-C values handled by the MMRM under MAR. Hierarchical testing (in the order of decreasing dose of study treatment) controls two-sided alpha = 0.05.p-value: <0.00195% CI: [-43.61, -26.93]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline LDL-C, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 LDL-C values handled by the MMRM under MAR. Hierarchical testing (in the order of decreasing dose of study treatment) controls two-sided alpha = 0.05.p-value: <0.00195% CI: [-46.31, -29.51]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline LDL-C, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 LDL-C values handled by the MMRM under MAR. Hierarchical testing (in the order of decreasing dose of study treatment) controls two-sided alpha = 0.05.p-value: <0.00195% CI: [-53.47, -36.86]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline LDL-C, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 LDL-C values handled by the MMRM under MAR. Hierarchical testing (in the order of decreasing dose of study treatment) controls two-sided alpha = 0.05.p-value: <0.00195% CI: [-59.03, -42.37]Mixed Models Analysis
Secondary
AZD0780 Plasma Concentrations Summarized by Sampling Timepoint
Geometric mean plasma concentration; LLOQ = 0.01 umol/L; BLQ values are handled as Not Quantified (NQ)
Time frame: From week 1 up to week 12
Population: PK Analysis Set: all participants who received at least one dose of study treatment and who had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0780 1 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 8 | 0.0932 umol/L | Geometric Coefficient of Variation 68.627 |
| AZD0780 1 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 2 | 0.0926 umol/L | Geometric Coefficient of Variation 71.7485 |
| AZD0780 1 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 12 | 0.0957 umol/L | Geometric Coefficient of Variation 61.8573 |
| AZD0780 1 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 4 | 0.0901 umol/L | Geometric Coefficient of Variation 81.297 |
| AZD0780 1 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 1 | 0.0790 umol/L | Geometric Coefficient of Variation 76.7603 |
| AZD0780 3 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 4 | 0.2380 umol/L | Geometric Coefficient of Variation 98.8448 |
| AZD0780 3 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 8 | 0.2359 umol/L | Geometric Coefficient of Variation 102.5351 |
| AZD0780 3 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 12 | 0.2317 umol/L | Geometric Coefficient of Variation 111.2636 |
| AZD0780 3 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 2 | 0.2639 umol/L | Geometric Coefficient of Variation 75.6804 |
| AZD0780 3 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 1 | 0.2523 umol/L | Geometric Coefficient of Variation 54.0463 |
| AZD0780 10 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 4 | 0.8393 umol/L | Geometric Coefficient of Variation 74.6636 |
| AZD0780 10 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 1 | 0.8120 umol/L | Geometric Coefficient of Variation 72.6051 |
| AZD0780 10 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 2 | 0.8156 umol/L | Geometric Coefficient of Variation 95.1545 |
| AZD0780 10 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 8 | 0.8350 umol/L | Geometric Coefficient of Variation 92.964 |
| AZD0780 10 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 12 | 0.7221 umol/L | Geometric Coefficient of Variation 119.9436 |
| AZD0780 30 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 8 | 2.4911 umol/L | Geometric Coefficient of Variation 102.642 |
| AZD0780 30 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 2 | 2.6676 umol/L | Geometric Coefficient of Variation 55.8538 |
| AZD0780 30 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 1 | 2.6420 umol/L | Geometric Coefficient of Variation 58.0213 |
| AZD0780 30 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 4 | 2.7059 umol/L | Geometric Coefficient of Variation 47.5671 |
| AZD0780 30 mg | AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Week 12 | 2.4373 umol/L | Geometric Coefficient of Variation 134.1014 |
Secondary
Percent Change From Baseline of Apolipoprotein A1 at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Apolipoprotein A1 at Week 12 | 2.52 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Apolipoprotein A1 at Week 12 | 2.89 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Apolipoprotein A1 at Week 12 | 3.79 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Apolipoprotein A1 at Week 12 | 5.55 Percent Change (%) |
| Placebo | Percent Change From Baseline of Apolipoprotein A1 at Week 12 | 3.82 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.50195% CI: [-5.08, 2.48]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.63495% CI: [-4.74, 2.89]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.9995% CI: [-3.74, 3.7]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.36695% CI: [-2.03, 5.5]Mixed Models Analysis
Secondary
Percent Change From Baseline of Apolipoprotein A1 at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Apolipoprotein A1 at Week 12 | 1.67 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Apolipoprotein A1 at Week 12 | 3.25 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Apolipoprotein A1 at Week 12 | 3.61 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Apolipoprotein A1 at Week 12 | 5.72 Percent Change (%) |
| Placebo | Percent Change From Baseline of Apolipoprotein A1 at Week 12 | 4.46 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.14695% CI: [-6.56, 0.98]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.5395% CI: [-4.98, 2.56]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.65495% CI: [-4.56, 2.87]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.50995% CI: [-2.48, 5]Mixed Models Analysis
Secondary
Percent Change From Baseline of Apolipoprotein B at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Apolipoprotein B at Week 12 | -24.08 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Apolipoprotein B at Week 12 | -25.39 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Apolipoprotein B at Week 12 | -34.33 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Apolipoprotein B at Week 12 | -36.95 Percent Change (%) |
| Placebo | Percent Change From Baseline of Apolipoprotein B at Week 12 | 2.92 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-33.08, -20.93]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-34.42, -22.2]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-43.27, -31.23]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-45.92, -33.83]Mixed Models Analysis
Secondary
Percent Change From Baseline of Apolipoprotein B at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Apolipoprotein B at Week 12 | -23.35 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Apolipoprotein B at Week 12 | -24.53 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Apolipoprotein B at Week 12 | -33.85 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Apolipoprotein B at Week 12 | -36.86 Percent Change (%) |
| Placebo | Percent Change From Baseline of Apolipoprotein B at Week 12 | 2.44 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-32.08, -19.51]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-33.33, -20.62]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-42.5, -30.08]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-45.61, -32.99]Mixed Models Analysis
Secondary
Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 0.12 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 4.03 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 1.97 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 4.66 Percent Change (%) |
| Placebo | Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 3.65 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.11195% CI: [-7.87, 0.81]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.86495% CI: [-3.98, 4.74]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.44595% CI: [-5.99, 2.63]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.64895% CI: [-3.32, 5.34]Mixed Models Analysis
Secondary
Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 0.80 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 3.66 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 2.17 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 4.65 Percent Change (%) |
| Placebo | Percent Change From Baseline of High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 3.11 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.29295% CI: [-6.62, 1.99]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.80295% CI: [-3.76, 4.86]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.66495% CI: [-5.21, 3.32]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.48195% CI: [-2.74, 5.82]Mixed Models Analysis
Secondary
Percent Change From Baseline of High Sensitivity C-reactive Protein (hsCRP) at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Descriptive statistics only.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment. For this outcome, only participants with both baseline and week 12 values were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of High Sensitivity C-reactive Protein (hsCRP) at Week 12 | 0.00 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of High Sensitivity C-reactive Protein (hsCRP) at Week 12 | 0.00 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of High Sensitivity C-reactive Protein (hsCRP) at Week 12 | 0.00 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of High Sensitivity C-reactive Protein (hsCRP) at Week 12 | -22.22 Percent Change (%) |
| Placebo | Percent Change From Baseline of High Sensitivity C-reactive Protein (hsCRP) at Week 12 | 0.00 Percent Change (%) |
Secondary
Percent Change From Baseline of Lipoprotein-a at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Descriptive statistics only.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment. For this outcome, only participants with both baseline and week 12 values were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Lipoprotein-a at Week 12 | -7.48 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Lipoprotein-a at Week 12 | -11.16 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Lipoprotein-a at Week 12 | -19.57 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Lipoprotein-a at Week 12 | -19.43 Percent Change (%) |
| Placebo | Percent Change From Baseline of Lipoprotein-a at Week 12 | 0.00 Percent Change (%) |
Secondary
Percent Change From Baseline of Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Percent change was calculated as (Week 12 LDL-C - Baseline LDL-C) / Baseline LDL-C \* 100. Negative values indicate reduction in LDL-C. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -30.47 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -33.35 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -40.47 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -46.41 Percent Change (%) |
| Placebo | Percent Change From Baseline of Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | 3.39 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline LDL-C, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-42.34, -25.37]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline LDL-C, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-45.3, -28.17]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline LDL-C, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-52.31, -35.41]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline LDL-C, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-58.35, -41.25]Mixed Models Analysis
Secondary
Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | -26.85 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | -29.86 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | -35.13 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | -41.65 Percent Change (%) |
| Placebo | Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | 3.53 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-38.63, -22.12]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-41.71, -25.08]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-46.9, -30.43]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-53.43, -36.94]Mixed Models Analysis
Secondary
Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | -26.13 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | -29.42 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | -34.77 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | -41.35 Percent Change (%) |
| Placebo | Percent Change From Baseline of Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | 2.86 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-37.16, -20.81]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-40.54, -24.02]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-45.82, -29.44]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-52.47, -35.94]Mixed Models Analysis
Secondary
Percent Change From Baseline of Remnant Cholesterol at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Descriptive statistics only.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment. For this outcome, only participants with both baseline and week 12 values were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Remnant Cholesterol at Week 12 | -9.09 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Remnant Cholesterol at Week 12 | -8.33 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Remnant Cholesterol at Week 12 | -22.95 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Remnant Cholesterol at Week 12 | -18.31 Percent Change (%) |
| Placebo | Percent Change From Baseline of Remnant Cholesterol at Week 12 | -5.00 Percent Change (%) |
Secondary
Percent Change From Baseline of Total Cholesterol at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Total Cholesterol at Week 12 | -18.93 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Total Cholesterol at Week 12 | -20.09 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Total Cholesterol at Week 12 | -24.84 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Total Cholesterol at Week 12 | -27.06 Percent Change (%) |
| Placebo | Percent Change From Baseline of Total Cholesterol at Week 12 | 2.29 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-26.27, -16.18]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-27.48, -17.3]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-32.16, -22.11]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: <0.00195% CI: [-34.4, -24.31]Mixed Models Analysis
Secondary
Percent Change From Baseline of Total Cholesterol at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Total Cholesterol at Week 12 | -18.23 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Total Cholesterol at Week 12 | -19.80 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Total Cholesterol at Week 12 | -24.54 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Total Cholesterol at Week 12 | -26.90 Percent Change (%) |
| Placebo | Percent Change From Baseline of Total Cholesterol at Week 12 | 1.73 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-25.09, -14.84]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-26.73, -16.35]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-31.37, -21.18]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: <0.00195% CI: [-33.8, -23.48]Mixed Models Analysis
Secondary
Percent Change From Baseline of Triglycerides at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Triglycerides at Week 12 | 2.81 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Triglycerides at Week 12 | 2.17 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Triglycerides at Week 12 | 1.72 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Triglycerides at Week 12 | -0.83 Percent Change (%) |
| Placebo | Percent Change From Baseline of Triglycerides at Week 12 | 9.04 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.27895% CI: [-17.5, 5.03]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.23495% CI: [-18.19, 4.45]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.19695% CI: [-18.41, 3.78]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.08695% CI: [-21.14, 1.41]Mixed Models Analysis
Secondary
Percent Change From Baseline of Triglycerides at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Triglycerides at Week 12 | 3.06 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Triglycerides at Week 12 | 2.90 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Triglycerides at Week 12 | 1.93 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Triglycerides at Week 12 | -0.44 Percent Change (%) |
| Placebo | Percent Change From Baseline of Triglycerides at Week 12 | 9.56 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.26695% CI: [-17.97, 4.96]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.25695% CI: [-18.17, 4.84]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.18695% CI: [-18.95, 3.69]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.08695% CI: [-21.44, 1.43]Mixed Models Analysis
Secondary
Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Treatment policy estimand: data collected after ICEs defined in the CSP retained.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | 0.81 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | 2.67 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | 1.77 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | 0.42 Percent Change (%) |
| Placebo | Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | 6.74 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.27595% CI: [-16.57, 4.71]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.45195% CI: [-14.63, 6.51]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.35195% CI: [-15.41, 5.47]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing data imputed using multiple imputation approach detailed in SAP Appendix 7.1.p-value: 0.24395% CI: [-16.92, 4.29]Mixed Models Analysis
Secondary
Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12
Percent change was calculated as (Week 12 value - Baseline value) / Baseline value \* 100. Negative values indicate reduction in lipid parameter. Baseline is the last non-missing value prior to first administration of study treatment. Hypothetical estimand: data collected after intercurrent events (ICEs) defined in the CSP excluded.
Time frame: From first day of treatment up to week 12
Population: Full Analysis Set: all randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AZD0780 1 mg | Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | 1.13 Percent Change (%) |
| AZD0780 3 mg | Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | 4.02 Percent Change (%) |
| AZD0780 10 mg | Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | 2.21 Percent Change (%) |
| AZD0780 30 mg | Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | 0.46 Percent Change (%) |
| Placebo | Percent Change From Baseline of Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Week 12 | 7.19 Percent Change (%) |
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.27695% CI: [-16.96, 4.84]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.56895% CI: [-14.08, 7.73]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.36395% CI: [-15.71, 5.75]Mixed Models Analysis
Comparison: MMRM with fixed effects for baseline of the respective parameter, treatment, visit, treatment-by-visit; random intercept for participants. Missing Week 12 values handled by the MMRM under MAR.p-value: 0.22395% CI: [-17.57, 4.11]Mixed Models Analysis