Clinical trial NCT02584504: Efficacy and Safety of Alirocumab in Patients With Hypercholesterolemia Not Adequately Controlled With Non-statin Lipid Modifying Therapy or the Lowest Strength of Statin
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab in Patients With Hypercholesterolemia Not Adequately Controlled With Non-statin Lipid Modifying Therapy or the Lowest Strength of Statin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Keywords: Non-statin LMT
Low dose statin
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2015-10-22
Enrollment: 163
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab administration as add-on therapy to non-statin lipid modifying therapy (LMT) including diet therapy alone or the lowest strength of statin in comparison with placebo after 12 weeks of treatment in participants with hypercholesterolemia.

Secondary Objective:

* To evaluate the effect of two treatment regimens of alirocumab on other lipid parameters: apolipoprotein B (Apo-B), non-high-density lipoprotein cholesterol (non HDL-C), total cholesterol (TC), lipoprotein (a) (Lp\[a\]), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and apolipoprotein A-1 (Apo A-1).
* To evaluate the safety and tolerability of alirocumab administration.
* To evaluate the development of anti-alirocumab antibodies.
* To evaluate the pharmacokinetic and pharmacodynamic profiles of alirocumab administration.
* To evaluate the long-term safety in participants receiving open-label alirocumab administration.

Detailed description: The duration of study per participant was approximately 71 weeks consisting of a run-in period (4 weeks), a screening period (3 weeks), a double-blind treatment period (12 weeks), and an open-label treatment period (52 weeks).

Eligibility criteria: Inclusion criteria :

Participants with hypercholesterolemia (heFH or non-FH) receiving non statin LMTs or the lowest strength of statin.

Exclusion criteria:

* LDL-C \<100 mg/dL (\<2.59 mmol/L) at the screening visit (Week -3) in participants with heFH or in participants with non-FH who have a history of documented coronary heart disease.
* LDL-C \<120 mg/dL (\<3.10 mmol/L) at the screening visit (Week -3) in participants with non-FH participants who had a history of documented diseases or other risk factors classified as primary prevention category III as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
* Not on a stable dose of LMT (including diet therapy alone) in the run-in period or the screening period.
* Fasting serum TGs \>400 mg/dL (\>4.52 mmol/L) at the screening period.
* Systolic blood pressure (BP) \>160 mmHg or diastolic BP \>100 mmHg at the run-in visit (Week -7) or the screening visit (Week -3) or the randomization visit (Week 0).

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 12- Intent to Treat (ITT) Analysis
timeFrame: From Baseline to Week 12
Secondary outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 12- On-Treatment Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12- On-Treatment Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apo-B at Week 12- On-Treatment Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Non-HDL-C at Week 12- On-treatment Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12- ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percentage of Participants Reaching Calculated LDL-C Goal at Week 12- ITT Analysis
timeFrame: Up to Week 12
measure: Percentage of Participants Reaching Calculated LDL-C Goal at Week 12- On-Treatment Analysis
timeFrame: Up to Week 12
measure: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12- ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Fasting Triglycerides (TGs) at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
measure: Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 12: ITT Analysis
timeFrame: From Baseline to Week 12
Other outcomes:
measure: Percent Change From Baseline in Calculated LDL-C at Week 20, 24, 36, 48 and 64 -OLTP Analysis
timeFrame: Baseline, Weeks 20, 24, 36, 48 and 64
Locations:
city: Ageo-Shi
country: Japan
facility: Investigational Site Number 392028
city: Chuo-Ku
country: Japan
facility: Investigational Site Number 392007
city: Chuo-Ku
country: Japan
facility: Investigational Site Number 392029
city: Fukui-Shi
country: Japan
facility: Investigational Site Number 392014
city: Hachioji-Shi
country: Japan
facility: Investigational Site Number 392023
city: Itoshima-Shi
country: Japan
facility: Investigational Site Number 392013
city: Kanazawa-Shi
country: Japan
facility: Investigational Site Number 392010
city: Kasuga-Shi
country: Japan
facility: Investigational Site Number 392024
city: Kawanishi-Shi
country: Japan
facility: Investigational Site Number 392004
city: Kitakyushu-Shi
country: Japan
facility: Investigational Site Number 392015
city: Komatsu-Shi
country: Japan
facility: Investigational Site Number 392005
city: Matsudo-Shi
country: Japan
facility: Investigational Site Number 392032
city: Matsumoto-Shi
country: Japan
facility: Investigational Site Number 392017
city: Mito-Shi
country: Japan
facility: Investigational Site Number 392003
city: Morioka-Shi
country: Japan
facility: Investigational Site Number 392018
city: Moriya-Shi
country: Japan
facility: Investigational Site Number 392009
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392006
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392011
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392019
city: Nagoya-Shi
country: Japan
facility: Investigational Site Number 392025
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392027
city: Sakura-Shi
country: Japan
facility: Investigational Site Number 392030
city: Shinagawa-Ku
country: Japan
facility: Investigational Site Number 392016
city: Shinjuku-Ku
country: Japan
facility: Investigational Site Number 392001
city: Shinjuku-Ku
country: Japan
facility: Investigational Site Number 392008
city: Shizuoka-Shi
country: Japan
facility: Investigational Site Number 392012
city: Suita-Shi
country: Japan
facility: Investigational Site Number 392002
city: Suita-Shi
country: Japan
facility: Investigational Site Number 392031
city: Toyonaka-Shi
country: Japan
facility: Investigational Site Number 392020
city: Yao-Shi
country: Japan
facility: Investigational Site Number 392022
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Teramoto T, Kondo A, Kiyosue A, Harada-Shiba M, Ishigaki Y, Tobita K, Kawabata Y, Ozaki A, Baccara-Dinet MT, Sata M. Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale. Lipids Health Dis. 2017 Jun 17;16(1):121. doi: 10.1186/s12944-017-0513-7.
citation: Teramoto T, Kiyosue A, Ishigaki Y, Harada-Shiba M, Kawabata Y, Ozaki A, Baccara-Dinet MT, Sata M. Efficacy and safety of alirocumab 150mg every 4 weeks in hypercholesterolemic patients on non-statin lipid-lowering therapy or lowest strength dose of statin: ODYSSEY NIPPON. J Cardiol. 2019 Mar;73(3):218-227. doi: 10.1016/j.jjcc.2018.10.004. Epub 2018 Nov 30.