Efficacy and Safety of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-lowering Therapy.
- Conditions
- Hypercholesterolemia
- Interventions
- Drug: Matching Placebo for InclisiranDrug: Matching Placebo for Ezetimibe
- Registration Number
- NCT05763875
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
CKJX839D12304 was a research study to determine if the study treatment, called inclisiran, in comparison to placebo and ezetimibe effectively reduces Low-Density Lipoprotein Cholesterol (LDL-C) as measured by percentage change from baseline to Day 150. This study was conducted in eligible participants with primary hypercholesterolemia not receiving any lipid-lowering therapy (LLT), with a 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk of less than 7.5%.
- Detailed Description
This study was a randomized, double-blind, placebo- and active comparator-controlled, multicenter study in 350 adult participants with primary hypercholesterolemia not receiving any LLT with a 10-year ASCVD risk score of less than 7.5%. This study evaluated the efficacy and safety of inclisiran sodium 300 mg, administered as a monotherapy in comparison to ezetimibe and placebo.
The study consisted of:
* a screening period of up to 14 days;
* a double-blind treatment period of 150+/- 5 days during which participants were randomly assigned to either the inclisiran arm, the ezetimibe arm or the placebo arm in a 2:1:1 ratio; and
* a safety follow-up / End of Study visit conducted 30+5 days after the Day 150 visit.
The overall study duration was approximately 190 days.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 350
Not provided
- history of ASCVD
- diabetes mellitus or fasting plasma glucose of >= 7.0 mmol/L or HbA1c >= 6.5%
- secondary hypercholesterolemia, e.g. hypothyroidism (TSH above upper limit of normal)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Inclisiran Matching Placebo for Ezetimibe Inclisiran s.c and Placebo p.o Placebo Matching Placebo for Ezetimibe Placebo s.c. and Placebo p.o. Placebo Matching Placebo for Inclisiran Placebo s.c. and Placebo p.o. Ezetimibe Matching Placebo for Inclisiran Placebo s.c. and Ezetimibe p.o. Inclisiran Inclisiran Inclisiran s.c and Placebo p.o Ezetimibe Ezetimibe Placebo s.c. and Ezetimibe p.o.
- Primary Outcome Measures
Name Time Method Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150 Baseline, Day 150 Percentage change in LDL-C from Baseline (day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.
There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows:
* Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
* Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.
- Secondary Outcome Measures
Name Time Method Absolute Change in LDL-C From Baseline to Day 150 Baseline, Day 150 Absolute change in LDL-C from Baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.
There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows:
* Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
* Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 150 Baseline, Day 150 Percentage change in PCSK9 from Baseline (Day 1) to Day 150 , Inclisiran arm versus Ezetimibe and placebo.
There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows:
* Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
* Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.Percentage Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Day 150 Baseline, Day 150 Percentage change in non-HDL-C from Baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.
There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows:
* Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
* Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.Percentage Change in Total Cholesterol (TC)/HDL-C Ratio From Baseline to Day 150 Baseline, Day 150 Percentage change in total cholesterol/HDL-C ratio from Baseline (Day1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.
There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows:
* Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
* Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable stratePercentage Change in Apolipoprotein B (Apo B) From Baseline to Day 150 Baseline, Day 150 Percentage change in Apo B from Baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.
There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows:
* Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
* Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.Percentage Change in Apo B/Apo A-1 Ratio From Baseline to Day 150 Baseline, Day 150 Percentage change in Apo B/Apo A-1 ratio from baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.
There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows:
* Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
* Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.Change in Lipoprotein (a) [Lp(a)] From Baseline to Day 150 Baseline, Day 150 Day 150 / Baseline ratio in Lp(a) in Inclisiran arm versus Ezetimibe and placebo.
There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows:
* Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
* Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.Incidence of Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) From first dose of study treatment on Day 1 up to Day 180 Incidence of TEAEs (regardless of seriousness) and SAEs by treatment group, including changes in laboratory results qualifying and reported as AEs.
Trial Locations
- Locations (23)
Parkway Medical Center
🇺🇸Birmingham, Alabama, United States
SEC Clinical Research
🇺🇸Dothan, Alabama, United States
Hillcrest Medical Research
🇺🇸DeLand, Florida, United States
ClinCloud
🇺🇸Maitland, Florida, United States
Inpatient Research Clinical LLC
🇺🇸Miami Lakes, Florida, United States
Alma Clinical Research Inc
🇺🇸Miami, Florida, United States
Harmony Clinical Research
🇺🇸North Miami Beach, Florida, United States
Fam Medical Specialists Of Fl Plc
🇺🇸Plant City, Florida, United States
Cozy Research LLC
🇺🇸Zephyrhills, Florida, United States
Koch Family Medicine
🇺🇸Morton, Illinois, United States
Scroll for more (13 remaining)Parkway Medical Center🇺🇸Birmingham, Alabama, United States