Clinical trial NCT01288469: Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) When Co-administered With High Dose of Atorvastatin in Patients With Primary Hypercholesterolemia
Official title: A Randomized, Double-blind, Parallel-group, Placebo-controlled, Fixed Dose/Dose Regimen, Multicenter Study Evaluating the Efficacy and Safety of SAR236553 When Co-administered With 80 mg of Atorvastatin Over 8 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥ 100 mg/dL (≥2.59 mmol/L) on Atorvastatin 10 mg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: 10020603
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2011-02-02
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels compared with placebo when co-administered with 80 mg of atorvastatin after 8 weeks of treatment in participants with LDL-C ≥ 100mg/dL (≥ 2.59 mmol/L) on atorvastatin 10 mg.

Secondary Objectives:

* To evaluate the effects of alirocumab on other lipid levels in comparison with placebo, when co-administered with 80 mg of atorvastatin after 8 weeks of treatment.
* To evaluate the efficacy of alirocumab when co-administered with a high dose of atorvastatin (80 mg) versus atorvastatin 10 mg.
* To evaluate the safety and tolerability of alirocumab when co-administered with 2 different doses of atorvastatin.
* To evaluate the development of anti-alirocumab antibodies.
* To evaluate the pharmacokinetics of alirocumab.

Detailed description: The duration of study participation depended on the status of the patient at screening:

* For participants receiving atorvastatin 10 mg at stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 17 weeks including a screening period of 1 week, a double-blind treatment period of 8 weeks and a follow-up period of 8 weeks.
* For participants receiving a lipid lowering treatment other than atorvastatin/ or not at stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 23 weeks with a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg of 6 weeks, a double-blind treatment period of 8 weeks and a follow-up period of 8 weeks.

Eligibility criteria: Inclusion criteria:

- Participants receiving a lipid-lowering treatment other than atorvastatin/ or not at stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening, or drug naive participants with primary hypercholesterolemia if they are likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the end of the 6-week run-in treatment period on atorvastatin therapy

OR

- Participants with primary hypercholesterolemia treated with stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening and likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the screening visit.

Exclusion criteria:

1. LDL-C \< 100 mg/dL (\< 2.59 mmol/L) at Week -1 (V1):

   * After the run-in period on atorvastatin 10 mg for participants receiving a lipid lowering treatment other than atorvastatin/ or not at stable dose of atorvastatin 10 mg for at least 6 weeks prior to the screening period, or drug naive participants.

   OR
   * At the first visit for participants who are being treated with atorvastatin 10 mg at stable dose for at least 6 weeks prior to screening visit.
2. Participants not previously instructed on a cholesterol-lowering diet.
3. Participants with type 1 diabetes.
4. Participants with type 2 diabetes treated with insulin.
5. Participants with type 2 diabetes and with an HbA1c ≥ 8.5% at screening visit (considered poorly controlled).
6. Laboratory findings measured before randomization:

   * Triglycerides (TG) \> 350 mg/dL (\> 3.95 mmol/L) at screening visit.
   * Positive serum or urine pregnancy test in females of childbearing potential.
7. Pregnant or breast-feeding women.
8. Women of childbearing potential with no effective contraceptive method.

The above information is 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 8 - On-treatment Analysis
timeFrame: From Baseline to Week 8 (LOCF)
Secondary outcomes:
measure: Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 8 - On-treatment Analysis
timeFrame: From baseline to Week 8 (LOCF)
measure: Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 8 - On-treatment Analysis
timeFrame: From baseline to Week 8 (LOCF)
measure: Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and < 70 mg/dL (1.81 mmol/L) at Week 8 - On-treatment Analysis
timeFrame: Week 8 (LOCF)
measure: Percent Change From Baseline in Total Cholesterol, Fasting Triglycerides, Non-high-Density Lipoprotein Cholesterol (Non-HDL-C), Apolipoprotein B (Apo-B) and Lipoprotein(a) at Week 8 - On-treatment Analysis
timeFrame: From baseline to Week 8 (LOCF)
measure: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 8 - On-treatment Analysis
timeFrame: From Baseline to Week 8 (LOCF)
measure: Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 8 - On-treatment Analysis
timeFrame: From Baseline to Week 8 (LOCF)
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Investigational Site Number 840616
state: Arizona
city: Tucson
country: United States
facility: Investigational Site Number 840601
state: Arizona
city: Los Angeles
country: United States
facility: Investigational Site Number 840610
state: California
city: Newport Beach
country: United States
facility: Investigational Site Number 840608
state: California
city: Doral
country: United States
facility: Investigational Site Number 840603
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840611
state: Florida
city: Jupiter
country: United States
facility: Investigational Site Number 840618
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 840612
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 840614
state: Florida
city: St. Petersburg
country: United States
facility: Investigational Site Number 840607
state: Florida
city: Chicago
country: United States
facility: Investigational Site Number 840605
state: Illinois
city: Chicago
country: United States
facility: Investigational Site Number 840619
state: Illinois
city: Edison
country: United States
facility: Investigational Site Number 840604
state: New Jersey
city: Rochester
country: United States
facility: Investigational Site Number 840606
state: New York
city: Cincinnati
country: United States
facility: Investigational Site Number 840615
state: Ohio
city: Cincinnati
country: United States
facility: Investigational Site Number 840617
state: Ohio
city: Eugene
country: United States
facility: Investigational Site Number 840602
state: Oregon
city: Richmond
country: United States
facility: Investigational Site Number 840621
state: Virginia
city: Olympia
country: United States
facility: Investigational Site Number 840609
state: Washington
city: Oregon
country: United States
facility: Investigational Site Number 840613
state: Wisconsin
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Roth EM, McKenney JM, Hanotin C, Asset G, Stein EA. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med. 2012 Nov 15;367(20):1891-900. doi: 10.1056/NEJMoa1201832. Epub 2012 Oct 31.
citation: Gaudet D, Kereiakes DJ, McKenney JM, Roth EM, Hanotin C, Gipe D, Du Y, Ferrand AC, Ginsberg HN, Stein EA. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials). Am J Cardiol. 2014 Sep 1;114(5):711-5. doi: 10.1016/j.amjcard.2014.05.060. Epub 2014 Jun 18.
citation: Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.
citation: Toth PP, Hamon SC, Jones SR, Martin SS, Joshi PH, Kulkarni KR, Banerjee P, Hanotin C, Roth EM, McKenney JM. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo. Lipids Health Dis. 2016 Feb 13;15:28. doi: 10.1186/s12944-016-0197-4.