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Study of the Efficacy and Safety of Alirocumab (REGN727/SAR236553) in Combination With Other Lipid-modifying Treatment (LMT) (ODYSSEY OPTIONS I)

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01730040
First received: November 9, 2012
Last updated: July 29, 2015
Last verified: July 2015

November 9, 2012
July 29, 2015
October 2012
April 2014   (final data collection date for primary outcome measure)
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
Calculated LDL-C values were obtained from Friedewald formula. Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Percent change in calculated LDL-C to wk 24 [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
Percent change in calculated LDL-C (low-density lipoprotein cholesterol) from baseline to week 24.
Complete list of historical versions of study NCT01730040 on ClinicalTrials.gov Archive Site
  • Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule [whatever atorvastatin, rosuvastatin or ezetimibe], whichever came first) (on-treatment analysis).
  • Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment (ITT analysis).
  • Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Calculated LDL-C values were obtained from Friedewald formula. Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule [whatever atorvastatin, rosuvastatin or ezetimibe], whichever came first) (on-treatment analysis).
  • Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (ie. up to 21 days after last injection or 3 days after the last capsule [whatever atorvastatin, rosuvastatin or ezetimibe], whichever came first).
  • Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection or 3 days after the last capsule [whatever atorvastatin, rosuvastatin or ezetimibe], whichever came first).
  • Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in Apo B at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in Total-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).
  • Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule [whatever atorvastatin, rosuvastatin or ezetimibe], whichever came first (on-treatment analysis).
  • Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to week 24 regardless of status on- or off-treatment were included in the imputation model (ITT analysis).
  • Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    Adjusted percentages at Week 24 were obtained from a multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 i.e. up to 21 days after last injection or 3 days after the last capsule [whatever atorvastatin, rosuvastatin or ezetimibe], whichever came first (on-treatment analysis).
  • Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted means and standard errors at Week 24 from from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted means and standard errors at Week 24 from from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in Lipoprotein(a) at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted means and standard errors at Week 12 from from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted means and standard errors at Week 12 from from a multiple imputation approach model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
  • Percent change in calculated LDL-C to wk 12 [ Time Frame: Baseline to week 12 ] [ Designated as safety issue: No ]
    Percent change in calculated LDL-C from baseline to week 12
  • Percent change in ApoB [ Time Frame: Baseline up to week 24 ] [ Designated as safety issue: No ]
    Percent change in ApoB (Apolipoprotein B) at time points up to week 24.
  • Proportion of patients reaching LDL-C goal [ Time Frame: At week 24 ] [ Designated as safety issue: No ]
    Proportion of patients reaching LDL-C goal at week 24.
  • Percent change in Lp(a) [ Time Frame: Baseline up to week 24 ] [ Designated as safety issue: No ]
    Percent change in LP(a) [(Lipoprotein(a)] at time points up to week 24
  • Percent change in non-HDL-C [ Time Frame: Baseline up to week 24 ] [ Designated as safety issue: No ]
    Percent change in non HDL-C (non-high-density lipoprotein cholesterol) at time points up to week 24
  • Percent change in HDL-C [ Time Frame: Baseline up to week 24 ] [ Designated as safety issue: No ]
    Percent change in HDL-C at time points up to week 24
  • Percent change in total-C [ Time Frame: Baseline up to week 24 ] [ Designated as safety issue: No ]
    Percent change in total-C at time points up to week 24
  • Percent change in TG [ Time Frame: Baseline up to week 24 ] [ Designated as safety issue: No ]
    Percent change in TG (Triglycerides) at time points up to week 24
  • Percent change in ApoA-1 [ Time Frame: Baseline up to week 24 ] [ Designated as safety issue: No ]
    Percent change in ApoA-1 at time points up to week 24
Not Provided
Not Provided
 
Study of the Efficacy and Safety of Alirocumab (REGN727/SAR236553) in Combination With Other Lipid-modifying Treatment (LMT) (ODYSSEY OPTIONS I)
A Randomized, Double-Blind Study of the Efficacy and Safety of Alirocumab Added on to Atorvastatin Versus Ezetimibe Added on to Atorvastatin Versus Atorvastatin Dose Increase Versus Switch to Rosuvastatin in Patients Who Are Not Controlled on Atorvastatin
This is a randomized, double-blind, active-comparator, parallel-group study in patients at high cardiovascular risk with nonfamilial hypercholesterolemia or heterozygous familial hypercholesterolemia (heFH).
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypercholesterolemia
  • Drug: Alirocumab
    Alirocumab administered as a SC injection of 1 mL into the abdomen, thigh, or outer area of the upper arm.
    Other Name: REGN727/SAR236553
  • Drug: Atorvastatin
    Atorvastatin over-encapsulated tablets orally.
  • Drug: Ezetimibe
    Ezetimibe over-encapsulated tablet orally.
    Other Name: Ezetrol
  • Drug: Rosuvastatin
    Rosuvastatin over-encapsulated tablets orally.
    Other Name: Crestor
  • Drug: Placebo
    Placebo for alirocumab and ezetimibe.
  • Active Comparator: Atorvastatin 40 mg
    Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received atorvastatin 40 mg over-encapsulated tablets orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablets orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Drug: Placebo
  • Active Comparator: Ezetimibe 10 mg + Atorvastatin 20 mg
    Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Drug: Ezetimibe
    • Drug: Placebo
  • Experimental: Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg
    Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received Alirocumab 75 mg SC injection Q2W, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
    Interventions:
    • Drug: Alirocumab
    • Drug: Atorvastatin
    • Drug: Placebo
  • Active Comparator: Atorvastatin 80 mg
    Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received Atorvastatin 80 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Drug: Placebo
  • Active Comparator: Rosuvastatin 40 mg
    Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received rosuvastatin 40 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.
    Interventions:
    • Drug: Rosuvastatin
    • Drug: Placebo
  • Active Comparator: Ezetimibe 10 mg + Atorvastatin 40 mg
    Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
    Interventions:
    • Drug: Atorvastatin
    • Drug: Ezetimibe
    • Drug: Placebo
  • Experimental: Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg
    Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received alirocumab 75 mg SC injection Q2W, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
    Interventions:
    • Drug: Alirocumab
    • Drug: Atorvastatin
    • Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
355
May 2014
April 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Patients with screening (visit 1) LDL-C greater than or equal to 70 mg/dL with documented CVD, not adequately controlled with a daily dose of atorvastatin. OR
  2. Patients with screening (visit 1) LDL-C greater than or equal to 100 mg/dL at high risk for CVD who are not adequately controlled with a daily dose of atorvastatin.

Exclusion Criteria:

  1. LDL-C greater than 250 mg/dL
  2. LDL-C less than 70 mg/dL at the screening visit in patients with history of documented CVD
  3. LDL-C less than 100 mg/dL at the screening visit in patients without history of documented CHD or non-CHD CVD, but with other risk factors
  4. TG greater than 400 mg/dL
  5. Homozygous FH (clinically or previous genotyping)
  6. Currently taking a statin that is not atorvastatin
  7. Currently taking Ezetimibe (EZE)
  8. Not on a stable dose of allowable lipid modifying treatments (LMT)

(The inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial).

Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   France,   Germany,   Italy,   Mexico,   Spain,   United Kingdom
Brazil
 
NCT01730040
R727-CL-1110
Yes
Not Provided
Not Provided
Regeneron Pharmaceuticals
Regeneron Pharmaceuticals
Sanofi
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
Regeneron Pharmaceuticals
July 2015

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