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Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy in Japan

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01812707
First received: March 14, 2013
Last updated: September 27, 2016
Last verified: August 2015

March 14, 2013
September 27, 2016
March 2013
January 2014   (final data collection date for primary outcome measure)
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (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 12 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 12 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01812707 on ClinicalTrials.gov Archive Site
  • Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (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 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (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 12 - On-Treatment Analysis [ Time Frame: Week 12 (LOCF) ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C), Non-HDL-C, and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
  • Percent Change From Baseline in Fasting Triglycerides and Lipoprotein (a) at Week 12 - On-Treatment Analysis [ Time Frame: Baseline to Week 12 (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 (inter-quartile range).
  • Absolute Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) Ratio at Week 12 - On-Treatment Analysis [ Time Frame: From Baseline to Week 12 (LOCF) ] [ Designated as safety issue: No ]
    Adjusted LS mean 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 12 ] [ Designated as safety issue: No ]
  • Percent and absolute changes in other lipid parameters [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy in Japan
A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study Evaluating the Efficacy and Safety of Three Doses of SAR236553 (REGN727) Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥100 mg/dL (≥2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9).

Primary Objective of the study:

To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥100 mg/dL (≥2.59 mmol/L) on ongoing stable atorvastatin therapy.

Secondary Objectives:

  • To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo
  • To evaluate the safety and tolerability of alirocumab
  • 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 participant at screening: 21 to 27 weeks including a screening/run-in period of 1 to 7 weeks, a double-blind treatment period of 12 weeks, followed by an 8-week follow-up period.
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Hypercholesterolemia
  • Drug: Alirocumab
    Two SC injections in the abdomen only
    Other Names:
    • SAR236553
    • RGEN727
  • Drug: Placebo (for alirocumab)

    Two subcutaneous (SC) injections in the abdomen only

    Route of administration: subcutaneous injection (1 mL) in the abdomen

  • Drug: Atorvastatin

    Orally once daily at a stable dose of 5 to 20 mg as background therapy

    Route of administration: oral administration in the evening

  • Placebo Comparator: Placebo
    Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.
    Interventions:
    • Drug: Placebo (for alirocumab)
    • Drug: Atorvastatin
  • Experimental: Alirocumab 50 mg Q2W
    Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
    Interventions:
    • Drug: Alirocumab
    • Drug: Atorvastatin
  • Experimental: Alirocumab 75 mg Q2W
    Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
    Interventions:
    • Drug: Alirocumab
    • Drug: Atorvastatin
  • Placebo Comparator: Alirocumab 150 mg Q2W
    Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
    Interventions:
    • Drug: Alirocumab
    • Drug: Atorvastatin
Teramoto T, Kobayashi M, Uno K, Takagi Y, Matsuoka O, Sugimoto M, Inoue S, Minami F, Baccara-Dinet MT. Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies). Am J Cardiol. 2016 Jul 1;118(1):56-63. doi: 10.1016/j.amjcard.2016.04.011.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
100
January 2014
January 2014   (final data collection date for primary outcome measure)

Inclusion criteria :

- Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 5-20 mg for at least 6 weeks prior to screening and likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) at the screening visit.

OR

- Participants with primary hypercholesterolemia who were receiving a lipid-lowering treatment other than atorvastatin, or who were not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening if they were likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) after a 6-week run-in treatment period on atorvastatin therapy.

Exclusion criteria:

  1. LDL-C <100 mg/dL (<2.59 mmol/L)

    • at screening visit for participants who were being treated with stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening OR
    • at the end of the 6-week run-in period on atorvastatin for participants receiving a lipid lowering treatment other than atorvastatin, or not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening
  2. Participants with type 1 diabetes
  3. Participants with type 2 diabetes treated with insulin, or without, and considered poorly controlled at screening.

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

Both
20 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT01812707
DFI12361, U1111-1134-4749
Yes
Not Provided
Not Provided
Sanofi
Sanofi
Regeneron Pharmaceuticals
Study Director: Clinical Sciences & Operations Sanofi
Sanofi
August 2015

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