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

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01288469
First received: February 1, 2011
Last updated: August 21, 2015
Last verified: January 2015

February 1, 2011
August 21, 2015
January 2011
September 2011   (final data collection date for primary outcome measure)
Percent Change From Baseline in Calculated LDL-C at Week 8 - On-treatment Analysis [ Time Frame: From Baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
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.
Percent change in calculated low-density lipoprotein cholesterol (LDL-C) [ Time Frame: from baseline to Week 8 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01288469 on ClinicalTrials.gov Archive Site
  • Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 8 - On-treatment Analysis [ Time Frame: From baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
  • Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 8 - On-treatment Analysis [ Time Frame: From baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
  • 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 [ Time Frame: Week 8 (LOCF) ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: From baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    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).
  • Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 8 - On-treatment Analysis [ Time Frame: From Baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
  • Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 8 - On-treatment Analysis [ Time Frame: From Baseline to Week 8 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA as for primary endpoint.
  • Absolute change in calculated low-density lipoprotein cholesterol (LDL-C) [ Time Frame: from baseline to Week 8 ] [ Designated as safety issue: No ]
  • Proportion of patients achieving an low-density lipoprotein cholesterol (LDL-C) level lower than 100mg/dL (2.59 mmol/L) [ Time Frame: at week 8 ] [ Designated as safety issue: No ]
  • Proportion of patients achieving an low-density lipoprotein cholesterol (LDL-C) level lower than 70mg/dL (1.81 mmol/L) [ Time Frame: at week 8 ] [ Designated as safety issue: No ]
  • Percent change in Total Cholesterol (TC) [ Time Frame: from baseline to Week 8 ] [ Designated as safety issue: No ]
  • Percent change in Triglycerides (TG) [ Time Frame: from baseline to Week 8 ] [ Designated as safety issue: No ]
  • Percent change in High-density lipoprotein cholesterol (HDL-C) [ Time Frame: from baseline to Week 8 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) When Co-administered With High Dose of Atorvastatin in Patients With Primary Hypercholesterolemia
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

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.

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.
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypercholesterolemia
  • Drug: Alirocumab
    One subcutaneous (SC) injection in the abdomen only.
    Other Names:
    • SAR236553
    • REGN727
  • Drug: Placebo (for alirocumab)
    One SC injection in the abdomen only.
  • Drug: Atorvastatin
    Over-encapsulated tablet orally once daily in the evening with dinner.
  • Drug: Placebo (for atorvastatin)
    One over-encapsulated tablet of placebo for atorvastatin orally once daily in the evening with dinner.
  • Placebo Comparator: Placebo + Atorvastatin 80 mg
    Placebo (for alirocumab) subcutaneous (SC) administration every 2 weeks (Q2W) in combination with atorvastatin 80 mg orally once daily for 8 weeks.
    Interventions:
    • Drug: Placebo (for alirocumab)
    • Drug: Atorvastatin
  • Experimental: Alirocumab + Atorvastatin 10 mg
    Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 10 mg orally once daily for 8 weeks.
    Interventions:
    • Drug: Alirocumab
    • Drug: Atorvastatin
    • Drug: Placebo (for atorvastatin)
  • Experimental: Alirocumab + Atorvastatin 80 mg
    Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 80 mg orally once daily for 8 weeks.
    Interventions:
    • Drug: Alirocumab
    • Drug: Atorvastatin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
92
September 2011
September 2011   (final data collection date for primary outcome measure)

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.

Both
18 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01288469
DFI11566, U1111-1117-9994
Yes
Not Provided
Not Provided
Sanofi
Sanofi
Regeneron Pharmaceuticals
Study Director: Clinical Sciences & Operations Sanofi
Sanofi
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP