Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) When Co-administered With High Dose of Atorvastatin in Patients With Primary Hypercholesterolemia

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01288469
• Other study ID #: DFI11566
• Secondary ID: U1111-1117-9994
• Status: Completed
• Phase: Phase 2
• First received: February 1, 2011
• Last updated: August 21, 2015
• Start date: January 2011
• Est. completion date: September 2011

Study information

• Verified date: January 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Alirocumab
One subcutaneous (SC) injection in the abdomen only.
• Placebo (for alirocumab)
One SC injection in the abdomen only.
• Atorvastatin
Over-encapsulated tablet orally once daily in the evening with dinner.
• Placebo (for atorvastatin)
One over-encapsulated tablet of placebo for atorvastatin orally once daily in the evening with dinner.

Locations

Country	Name	City	State
United States	Investigational Site Number 840605	Chicago	Illinois
United States	Investigational Site Number 840619	Chicago	Illinois
United States	Investigational Site Number 840615	Cincinnati	Ohio
United States	Investigational Site Number 840617	Cincinnati	Ohio
United States	Investigational Site Number 840603	Doral	Florida
United States	Investigational Site Number 840604	Edison	New Jersey
United States	Investigational Site Number 840602	Eugene	Oregon
United States	Investigational Site Number 840611	Jacksonville	Florida
United States	Investigational Site Number 840618	Jupiter	Florida
United States	Investigational Site Number 840610	Los Angeles	California
United States	Investigational Site Number 840616	Mesa	Arizona
United States	Investigational Site Number 840612	Miami	Florida
United States	Investigational Site Number 840614	Miami	Florida
United States	Investigational Site Number 840608	Newport Beach	California
United States	Investigational Site Number 840609	Olympia	Washington
United States	Investigational Site Number 840613	Oregon	Wisconsin
United States	Investigational Site Number 840621	Richmond	Virginia
United States	Investigational Site Number 840606	Rochester	New York
United States	Investigational Site Number 840607	St. Petersburg	Florida
United States	Investigational Site Number 840601	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 e — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Calculated LDL-C at Week 8 - On-treatment Analysis	Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational product (IP) injection up to 21 days after last IP injection (on-treatment analysis). Missing Week 8 data were imputed by last observation carried forward [LOCF] method.	From Baseline to Week 8 (LOCF)	No
Secondary	Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 8 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From baseline to Week 8 (LOCF)	No
Secondary	Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 8 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From baseline to Week 8 (LOCF)	No
Secondary	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		Week 8 (LOCF)	No
Secondary	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	Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range).	From baseline to Week 8 (LOCF)	No
Secondary	Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 8 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.	From Baseline to Week 8 (LOCF)	No
Secondary	Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 8 - On-treatment Analysis	Adjusted LS means and standard errors were estimated using the same ANCOVA as for primary endpoint.	From Baseline to Week 8 (LOCF)	No