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Trial record 1 of 1 for:    EFC14305
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Efficacy and Safety of Alirocumab in Patients With Hypercholesterolemia Not Adequately Controlled With Non-statin Lipid Modifying Therapy or the Lowest Strength of Statin (ODYSSEY-NIPPON)

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ClinicalTrials.gov Identifier: NCT02584504
Recruitment Status : Completed
First Posted : October 22, 2015
Results First Posted : May 7, 2018
Last Update Posted : January 23, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab administration as add-on therapy to non-statin lipid modifying therapy (LMT) including diet therapy alone or the lowest strength of statin in comparison with placebo after 12 weeks of treatment in participants with hypercholesterolemia.

Secondary Objective:

  • To evaluate the effect of two treatment regimens of alirocumab on other lipid parameters: apolipoprotein B (Apo-B), non-high-density lipoprotein cholesterol (non HDL-C), total cholesterol (TC), lipoprotein (a) (Lp[a]), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and apolipoprotein A-1 (Apo A-1).
  • To evaluate the safety and tolerability of alirocumab administration.
  • To evaluate the development of anti-alirocumab antibodies.
  • To evaluate the pharmacokinetic and pharmacodynamic profiles of alirocumab administration.
  • To evaluate the long-term safety in participants receiving open-label alirocumab administration.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Drug: Alirocumab Drug: Placebo Drug: Atorvastatin Drug: Non-statin Lipid-Modifying Therapy Other: Diet Alone Phase 3

Detailed Description:
The duration of study per participant was approximately 71 weeks consisting of a run-in period (4 weeks), a screening period (3 weeks), a double-blind treatment period (12 weeks), and an open-label treatment period (52 weeks).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 163 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab in Patients With Hypercholesterolemia Not Adequately Controlled With Non-statin Lipid Modifying Therapy or the Lowest Strength of Statin
Actual Study Start Date : November 30, 2015
Actual Primary Completion Date : April 5, 2017
Actual Study Completion Date : January 9, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Alirocumab

Arm Intervention/treatment
Experimental: Alirocumab 150 mg Q4W
Double-blind treatment period(DBTP):participants received Alirocumab 150 mg subcutaneous injection every 4 week(Q4W) alternating with placebo(for alirocumab)Q4W added to lowest-strength statin therapy(atorvastatin 5 mg daily),stable non-statin LMT/diet therapy alone for 12weeks. Participants completed DBTP,entered open-label treatment period(OLTP),received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg every 2 weeks(Q2W) at Week 24(OLTP:Week 12),when targeted LDL-C level at Week 20 not achieved as Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012:1) ≥100 mg/dL(2.59 mmol/L) in heterozygous familial hypercholesterolemia (heFH) participants/non-familial hypercholesterolemia (non-FH)participants with history of documented coronary heart disease;2) ≥120 mg/dL(3.10 mmol/L)in non-FH participants with history of documented diseases/other risk factors as categorized in primary prevention category III)
Drug: Alirocumab
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.
Other Names:
  • SAR236553
  • REGN727

Drug: Placebo
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.

Drug: Atorvastatin
Atorvastatin 5 mg tablet orally.

Drug: Non-statin Lipid-Modifying Therapy
Ezetimibe, Bezafibrate or Fenofibrate at stable dose as background therapy.

Other: Diet Alone
Stable cholesterol-lowering diet as background therapy.

Experimental: Alirocumab 150 mg Q2W
In DBTP, participants received Alirocumab 150 mg subcutaneous (SC) injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks. Participants who completed DBTP were entered in OLTP and received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when targeted LDL-C levels at Week 20 were not achieved i.e. LDL-C ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) according to Japan Atherosclerosis Society(JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Drug: Alirocumab
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.
Other Names:
  • SAR236553
  • REGN727

Drug: Atorvastatin
Atorvastatin 5 mg tablet orally.

Drug: Non-statin Lipid-Modifying Therapy
Ezetimibe, Bezafibrate or Fenofibrate at stable dose as background therapy.

Other: Diet Alone
Stable cholesterol-lowering diet as background therapy.

Placebo Comparator: Placebo Q2W
In DBTP, participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks. Participants who completed DBTP were entered in OLTP and received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when targeted LDL-C levels at Week 20 were not achieved i.e. LDL-C ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
Drug: Placebo
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.

Drug: Atorvastatin
Atorvastatin 5 mg tablet orally.

Drug: Non-statin Lipid-Modifying Therapy
Ezetimibe, Bezafibrate or Fenofibrate at stable dose as background therapy.

Other: Diet Alone
Stable cholesterol-lowering diet as background therapy.




Primary Outcome Measures :
  1. Percent Change From Baseline in Calculated LDL-C at Week 12- Intent to Treat (ITT) Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted Least-squares (LS) means and standard errors at Week 12 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 12 regardless of status on- or off-treatment were used in the model (ITT analysis).


Secondary Outcome Measures :
  1. Percent Change From Baseline in Calculated LDL-C at Week 12- On-Treatment Analysis [ Time Frame: From Baseline to Week 12 ]
    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 12 (i.e. up to 21 days after last double-blind injection).

  2. Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment and assigning a weight of 0.5 for Week 10 and 12 time points.

  3. Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12- On-Treatment Analysis [ Time Frame: From Baseline to Week 12 ]
    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 12 (i.e. up to 21 days after last double-blind injection) and assigning a weight of 0.5 for Week 10 and 12 time points.

  4. Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.

  5. Percent Change From Baseline in Apo-B at Week 12- On-Treatment Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data at from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection).

  6. Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.

  7. Percent Change From Baseline in Non-HDL-C at Week 12- On-treatment Analysis [ Time Frame: From Baseline to Week 12 ]
    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 12 (i.e. up to 21 days after last double-blind injection).

  8. Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12- ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.

  9. Percentage of Participants Reaching Calculated LDL-C Goal at Week 12- ITT Analysis [ Time Frame: Up to Week 12 ]
    Calculated LDL-C goal was defined as calculated LDL-C <100 mg/dL (2.59 mmol/L) for heterozygous familiar hypercholesterolemia (heFH) participants or non-familial hypercholesterolemia (non-FH) participants who had a history of documented CHD, or <120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. Adjusted percentages at Week 12 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment were included in the imputation model.

  10. Percentage of Participants Reaching Calculated LDL-C Goal at Week 12- On-Treatment Analysis [ Time Frame: Up to Week 12 ]
    Calculated LDL-C goal was defined as calculated LDL-C <100 mg/dL (2.59 mmol/L) for heFH participants or non-FH participants who had a history of documented CHD, or <120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. Adjusted percentages at Week 12 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 12 (i.e. up to 21 days after last double-blind injection).

  11. Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted means and standard errors at Week 12 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment were included in the imputation model.

  12. Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12- ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.

  13. Percent Change From Baseline in Fasting Triglycerides (TGs) at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.

  14. Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 12: ITT Analysis [ Time Frame: From Baseline to Week 12 ]
    Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment.


Other Outcome Measures:
  1. Percent Change From Baseline in Calculated LDL-C at Week 20, 24, 36, 48 and 64 -OLTP Analysis [ Time Frame: Baseline, Weeks 20, 24, 36, 48 and 64 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

Participants with hypercholesterolemia (heFH or non-FH) receiving non statin LMTs or the lowest strength of statin.

Exclusion criteria:

  • LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (Week -3) in participants with heFH or in participants with non-FH who have a history of documented coronary heart disease.
  • LDL-C <120 mg/dL (<3.10 mmol/L) at the screening visit (Week -3) in participants with non-FH participants who had a history of documented diseases or other risk factors classified as primary prevention category III as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
  • Not on a stable dose of LMT (including diet therapy alone) in the run-in period or the screening period.
  • Fasting serum TGs >400 mg/dL (>4.52 mmol/L) at the screening period.
  • Systolic blood pressure (BP) >160 mmHg or diastolic BP >100 mmHg at the run-in visit (Week -7) or the screening visit (Week -3) or the randomization visit (Week 0).

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02584504


Locations
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Japan
Investigational Site Number 392028
Ageo-Shi, Japan
Investigational Site Number 392007
Chuo-Ku, Japan
Investigational Site Number 392029
Chuo-Ku, Japan
Investigational Site Number 392014
Fukui-Shi, Japan
Investigational Site Number 392023
Hachioji-Shi, Japan
Investigational Site Number 392013
Itoshima-Shi, Japan
Investigational Site Number 392010
Kanazawa-Shi, Japan
Investigational Site Number 392024
Kasuga-Shi, Japan
Investigational Site Number 392004
Kawanishi-Shi, Japan
Investigational Site Number 392015
Kitakyushu-Shi, Japan
Investigational Site Number 392005
Komatsu-Shi, Japan
Investigational Site Number 392032
Matsudo-Shi, Japan
Investigational Site Number 392017
Matsumoto-Shi, Japan
Investigational Site Number 392003
Mito-Shi, Japan
Investigational Site Number 392018
Morioka-Shi, Japan
Investigational Site Number 392009
Moriya-Shi, Japan
Investigational Site Number 392006
Nagoya-Shi, Japan
Investigational Site Number 392011
Nagoya-Shi, Japan
Investigational Site Number 392019
Nagoya-Shi, Japan
Investigational Site Number 392025
Nagoya-Shi, Japan
Investigational Site Number 392027
Osaka-Shi, Japan
Investigational Site Number 392030
Sakura-Shi, Japan
Investigational Site Number 392016
Shinagawa-Ku, Japan
Investigational Site Number 392001
Shinjuku-Ku, Japan
Investigational Site Number 392008
Shinjuku-Ku, Japan
Investigational Site Number 392012
Shizuoka-Shi, Japan
Investigational Site Number 392002
Suita-Shi, Japan
Investigational Site Number 392031
Suita-Shi, Japan
Investigational Site Number 392020
Toyonaka-Shi, Japan
Investigational Site Number 392022
Yao-Shi, Japan
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] April 26, 2017
Statistical Analysis Plan  [PDF] June 17, 2016


Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02584504     History of Changes
Other Study ID Numbers: EFC14305
U1111-1170-7697 ( Other Identifier: UTN )
First Posted: October 22, 2015    Key Record Dates
Results First Posted: May 7, 2018
Last Update Posted: January 23, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Sanofi:
Non-statin LMT
Low dose statin

Additional relevant MeSH terms:
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Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs