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OpenTrials
Completed

NCT Number: NCT02585778

Efficacy and Safety of Alirocumab Versus Placebo on Top of Maximally Tolerated Lipid Lowering Therapy in Patients With Hypercholesterolemia Who Have Type 1 or Type 2 Diabetes and Are Treated With Insulin (ODYSSEY DM - Insulin)

Primary Objectives:

* To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in participants with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy. * To evaluate the safety and tolerability of alirocumab in participants with diabetes treated with insulin.

Secondary Objective:

To demonstrate that alirocumab was superior in comparison to placebo in its effects on other lipid parameters (i.e., measured LDL-C, non-high-density lipoprotein cholesterol [non-HDL-C], apolipoprotein B [Apo B], total cholesterol [TC], lipoprotein a [Lp(a)], high density lipoprotein cholesterol [HDL-C], triglyceride [TG] levels, triglyceride rich lipoproteins [TGRL], apolipoprotein A-1 [Apo A-1], apolipoprotein C-III [Apo C-III], and LDL particle number and size).

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Key information

Conditions

Hypercholesterolaemia Dyslipidemias Hypercholesterolemia Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Investigational Site Number 040002, Innsbruck, Austria

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About this study

The maximum study duration was approximately 9 months per participant, including a 6 month treatment period, a screening period of up to 3 weeks, and an 8 week safety observation period.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants diagnosed with Type 1 or Type 2 diabetes at least one year prior to the screening visit (Week -3).
  • Signed written informed consent
  • Participants with type 1 or type 2 diabetes treated with insulin whose LDL-C levels were not adequately controlled with maximally tolerated lipid-modifying therapy
  • LDL-C of 70 mg/dL or greater
  • 18 years of age or more
  • Glycosylated hemoglobin (HbA1c) less than 10%
  • History of cardiovascular disease (including coronary heart disease [CHD] and/or CHD risk equivalents) and/or at least one additional cardiovascular risk factor

Exclusion criteria

  • Not on a stable dose of statin or other lipid modifying therapy for at least 4 weeks prior to screening or from screening to randomization, unless statin intolerant
  • Triglycerides >400 mg/dL
  • Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m² according to the Modification of Diet in Renal Disease (MDRD) equation
  • Currently received or planned to receive renal replacement therapy (for example, hemodialysis)
  • Change in weight of more than 5 kilograms within the prior 2 months
  • Not on a stable dose/regimen of insulin or other antidiabetic drugs for the past 3 months or planned to intensify insulin regimen during the study
  • Not treated with insulin for at least 6 months
  • Planned to start new lipid modifying therapy or change dose of current lipid modifying therapy during the study
  • Body mass index (BMI) >45 kg/m² or planned to undergo bariatric surgery, weight loss program, or initiate weight loss drugs during the study
  • History of recent decompensation of diabetes within the prior 2 months (for example, diabetic ketoacidosis)

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

Treatment and study plan

Alirocumab

Drug

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

Other names: Praluent, SAR236553, REGN727

Placebo

Drug

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

Lipid-Modifying Therapy (LMT)

Drug

Statins at stable, maximally tolerated dose with or without other LMT as clinically indicated.

Antihyperglycemic Drug

Drug

Insulin (injectable or inhaled) alone or with other antihyperglycemic drugs as clinically indicated.

Primary outcomes

  1. Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis

    Time frame: From Baseline to Week 24

    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).

  2. Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)

    Time frame: From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks)

    Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).

Secondary outcomes

  1. Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis

    Time frame: From Baseline to Week 24

    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).

  2. Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis

    Time frame: From Baseline to Week 24

    Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

  3. Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis

    Time frame: From Baseline to Week 24

    Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

  4. Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis

    Time frame: From Baseline to Week 24

    Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

  5. 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

    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.

  6. Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis

    Time frame: From Baseline to Week 24

    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.

  7. Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis

    Time frame: From Baseline to Week 24

    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.

  8. 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

    Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

  9. Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis

    Time frame: Up to Week 24

    Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach (for T1DM participants) and multiple imputation approach model (for T2DM participants) including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). The maximum likelihood estimate did not exist as response rate was zero in a treatment group of T1DM participants.

  10. Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis

    Time frame: Up to Week 24

    Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

  11. Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis

    Time frame: Up to Week 24

    Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

  12. Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis

    Time frame: From Baseline to Week 24

    Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach for handling of missing data followed by robust regression model. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.

  13. Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis

    Time frame: From Baseline to Week 24

    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.

  14. Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis

    Time frame: From Baseline to Week 24

    Adjusted means and standard errors at Week 24 from multiple imputation approach for handling of missing data followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

  15. Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis

    Time frame: From Baseline to Week 24

    LDL-C particle number was calculated from lipid subfractions by nuclear magnetic resonance (NMR) spectroscopy. 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.

  16. Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis

    Time frame: From Baseline to Week 24

    LDL-C particle size was calculated from lipid subfractions by NMR spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

  17. Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis

    Time frame: Baseline, Weeks 12 and 24

    Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.

  18. Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis

    Time frame: Baseline, Weeks 12 and 24

    Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.

  19. Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis

    Time frame: Baseline, Weeks 12 and 24

    Absolute change = FPG value at specified weeks minus FPG value at baseline.

  20. Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis

    Time frame: Baseline, Weeks 12 and 24

    Absolute change = FPG value at specified weeks minus FPG value at baseline.

  21. Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis

    Time frame: Baseline, Weeks 12 and 24

    Absolute change = total daily insulin dose at specified weeks minus baseline value.

  22. Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis

    Time frame: Baseline, Weeks 12 and 24

    Absolute change = total daily insulin dose at specified weeks minus baseline value.

  23. Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis

    Time frame: Baseline, Weeks 12 and 24

    Absolute change = daily insulin dose/kg at specified weeks minus baseline value.

  24. Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis

    Time frame: Baseline, Weeks 12 and 24

    Absolute change = daily insulin dose/kg at specified weeks minus baseline value.

  25. Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis

    Time frame: Baseline, Weeks 12 and 24

    Glucose lowering treatment was calculated for non-insulin treatments as one for each unique treatment received and for insulin treatment as one in total for all participants who have taken one or more treatments. Absolute change = number of glucose-lowering treatments at specified weeks minus baseline value.

  26. Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis

    Time frame: Baseline, Weeks 12 and 24

    Glucose lowering treatment was calculated for non-insulin treatments as one for each unique treatment received and for insulin treatment as one in total for all participants who have taken one or more treatments. Absolute change = number of glucose-lowering treatments at specified weeks minus baseline value.

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Collaborators

  • Regeneron Pharmaceuticals

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab in Insulin Treated Patients With Type 1 or Type 2 Diabetes and With Hypercholesterolemia at High Cardiovascular Risk Not Adequately Controlled on Maximally Tolerated LDL-C Lowering Therapy

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Oct 23, 2015
Registry last updated
May 17, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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