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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02642159




Registration number
NCT02642159
Ethics application status
Date submitted
24/12/2015
Date registered
30/12/2015
Date last updated
1/05/2018

Titles & IDs
Public title
Efficacy and Safety of Alirocumab Versus Usual Care on Top of Maximally Tolerated Statin Therapy in Patients With Type 2 Diabetes and Mixed Dyslipidemia (ODYSSEY DM-Dyslipidemia)
Scientific title
A Randomized, Open-Label, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab Versus Usual Care in Patients With Type 2 Diabetes and Mixed Dyslipidemia at High Cardiovascular Risk With Non-HDL-C Not Adequately Controlled With Maximally Tolerated Statin Therapy
Secondary ID [1] 0 0
2015-001934-19
Secondary ID [2] 0 0
LPS14354
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dyslipidemia 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Alirocumab
Treatment: Drugs - Statins
Treatment: Drugs - Ezetimibe
Treatment: Drugs - Fenofibrate
Treatment: Drugs - Nicotinic acid
Treatment: Drugs - Omega-3 fatty acids
Treatment: Drugs - Antihyperglycemic Drug

Experimental: Alirocumab 75 mg Q2W/Up to 150 mg Q2W - Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other lipid modifying therapy (LMT) for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-high-density lipoprotein cholesterol (non-HDL-C) levels >=100 mg/dL (2.59 mmol/L) at Week 8.

Active Comparator: Usual Care - Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.


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

Treatment: Drugs: Statins
Statins at stable dose without other LMT as clinically indicated.

Treatment: Drugs: Ezetimibe
Pharmaceutical form: tablet Route of administration: oral

Treatment: Drugs: Fenofibrate
Pharmaceutical form: tablet Route of administration: oral

Treatment: Drugs: Nicotinic acid
Pharmaceutical form: tablet Route of administration: oral

Treatment: Drugs: Omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral

Treatment: Drugs: Antihyperglycemic Drug
Insulin (injectable or inhaled) or other antihyperglycemic drugs as clinically indicated.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in Non-HDL-C at Week 24: Overall Intent-to-treat (ITT) Analysis - 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 8 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Timepoint [1] 0 0
From Baseline to Week 24
Primary outcome [2] 0 0
Percent Change From Baseline in Non-HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum - Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Timepoint [2] 0 0
From Baseline to Week 24
Secondary outcome [1] 0 0
Percent Change From Baseline in Measured Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24: Overall ITT Analysis - 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 8 to Week 24 regardless of status on- or off-treatment.
Timepoint [1] 0 0
From Baseline to Week 24
Secondary outcome [2] 0 0
Percent Change From Baseline in Measured LDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum - 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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Timepoint [2] 0 0
From Baseline to Week 24
Secondary outcome [3] 0 0
Percent Change From Baseline in Non-HDL-C at Week 12: Overall ITT Analysis - Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment.
Timepoint [3] 0 0
From Baseline to Week 24
Secondary outcome [4] 0 0
Percent Change From Baseline in Non-HDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum - Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Timepoint [4] 0 0
From Baseline to Week 24
Secondary outcome [5] 0 0
Percent Change From Baseline in Measured LDL-C at Week 12: Overall ITT Analysis - 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 8 to Week 24 regardless of status on- or off-treatment.
Timepoint [5] 0 0
From Baseline to Week 24
Secondary outcome [6] 0 0
Percent Change From Baseline in Measured LDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum - 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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Timepoint [6] 0 0
From Baseline to Week 24
Secondary outcome [7] 0 0
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24: Overall ITT Analysis - Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment.
Timepoint [7] 0 0
From Baseline to Week 24
Secondary outcome [8] 0 0
Percent Change From Baseline in Apo B at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum - Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Timepoint [8] 0 0
From Baseline to Week 24
Secondary outcome [9] 0 0
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 : Overall ITT Analysis - Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment.
Timepoint [9] 0 0
From Baseline to Week 24
Secondary outcome [10] 0 0
Percent Change From Baseline in Total-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum - Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Timepoint [10] 0 0
From Baseline to Week 24
Secondary outcome [11] 0 0
Percent Change From Baseline in Lipoprotein(a) at Week 24 : Overall ITT Analysis - Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Timepoint [11] 0 0
From Baseline to Week 24
Secondary outcome [12] 0 0
Percent Change From Baseline in Lipoprotein(a) at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum - Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Timepoint [12] 0 0
From Baseline to Week 24
Secondary outcome [13] 0 0
Percent Change From Baseline in Fasting Triglycerides at Week 24: Overall ITT Analysis - Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment.
Timepoint [13] 0 0
From Baseline to Week 24
Secondary outcome [14] 0 0
Percent Change From Baseline in Fasting Triglycerides at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum - Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Timepoint [14] 0 0
From Baseline to Week 24
Secondary outcome [15] 0 0
Percent Change From Baseline in HDL-C at Week 24 : Overall ITT Analysis - Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment.
Timepoint [15] 0 0
From Baseline to Week 24
Secondary outcome [16] 0 0
Percent Change From Baseline in HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum - Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Timepoint [16] 0 0
From Baseline to Week 24
Secondary outcome [17] 0 0
Percent Change From Baseline in LDL-C Particle Number at Week 24: Overall ITT Analysis - 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 8 to Week 24 regardless of status on- or off-treatment.
Timepoint [17] 0 0
From Baseline to Week 24
Secondary outcome [18] 0 0
Percent Change From Baseline in LDL-C Particle Number at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum - LDL-C particle number was calculated from lipid subfractions by NMR spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Timepoint [18] 0 0
From Baseline to Week 24
Secondary outcome [19] 0 0
Absolute Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 and 24 : Overall ITT Analysis - Absolute change = HbA1c value at specified week minus HbA1c value at baseline.
Timepoint [19] 0 0
Baseline, Week 12 and 24
Secondary outcome [20] 0 0
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 and 24 : Overall ITT Analysis - Absolute change = FPG value at specified week minus FPG value at baseline.
Timepoint [20] 0 0
Baseline, Week 12 and 24
Secondary outcome [21] 0 0
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Week 12 and 24 : Overall ITT Analysis - 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 week minus baseline value.
Timepoint [21] 0 0
Baseline, Week 12 and 24

Eligibility
Key inclusion criteria
Inclusion criteria:

- Participants with type 2 diabetes and mixed dyslipidemia whose non-HDL-C was not
adequately controlled with a stable, maximum dose/regimen of statin that was tolerated
by the participant.

- 18 years of age or more.

- Documented history of atherosclerotic cardiovascular disease (ASCVD) or at least one
additional cardiovascular risk factor.

- Non-HDL-C of 100 mg/dL or greater.

- Triglycerides greater than or equal to 150 mg/dL and less than 500 mg/dL.

- Stable anti-hyperglycemic agents for at least 3 months prior to the screening visit
and between screening and randomization (including stable insulin dose defined as no
variation more than 30% in daily insulin dose within the preceding 3 months, as judged
by the Investigator).

- No change in weight of more than 5 kg within the prior 3 months.

- On stable dose of medications that are known to influence weight and/or lipids within
the last 3 months.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Use of any lipid modifying therapies other than statins within the last 4 weeks (eg,
ezetimibe, fenofibrate, nicotinic acid, omega-3 fatty acids, etc.) or use of over the
counter products/nutraceuticals known to impact lipids (eg, red yeast rice) within the
last 4 weeks.

- Currently drinking more than 2 standard alcoholic drinks per day.

- Body Mass Index (BMI) >45 kg/m² or currently enrolled in a weight loss program and
still in active phase of weight loss.

- Glycosylated hemoglobin (HbA1c) 9% or greater.

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 036102 - Herston
Recruitment hospital [2] 0 0
Investigational Site Number 036104 - Merewether
Recruitment hospital [3] 0 0
Investigational Site Number 036101 - St Leonards
Recruitment postcode(s) [1] 0 0
4006 - Herston
Recruitment postcode(s) [2] 0 0
2291 - Merewether
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
Nevada
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
North Dakota
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Utah
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
Brazil
State/province [23] 0 0
Campinas
Country [24] 0 0
Brazil
State/province [24] 0 0
Fortaleza
Country [25] 0 0
Brazil
State/province [25] 0 0
Sao Paulo
Country [26] 0 0
Brazil
State/province [26] 0 0
São paulo
Country [27] 0 0
Brazil
State/province [27] 0 0
São Paulo
Country [28] 0 0
Brazil
State/province [28] 0 0
SãO Paulo
Country [29] 0 0
Finland
State/province [29] 0 0
Oulu
Country [30] 0 0
Finland
State/province [30] 0 0
Tampere
Country [31] 0 0
Germany
State/province [31] 0 0
Berlin
Country [32] 0 0
Germany
State/province [32] 0 0
Dippoldiswalde
Country [33] 0 0
Germany
State/province [33] 0 0
Dresden
Country [34] 0 0
Germany
State/province [34] 0 0
Essen
Country [35] 0 0
Germany
State/province [35] 0 0
Goch
Country [36] 0 0
Germany
State/province [36] 0 0
Karlsruhe
Country [37] 0 0
Germany
State/province [37] 0 0
Künzing
Country [38] 0 0
Germany
State/province [38] 0 0
Oldenburg in Holstein
Country [39] 0 0
Israel
State/province [39] 0 0
Beer Sheva
Country [40] 0 0
Israel
State/province [40] 0 0
Petach Tikva
Country [41] 0 0
Israel
State/province [41] 0 0
Petach tikva
Country [42] 0 0
Israel
State/province [42] 0 0
Rehovot
Country [43] 0 0
Israel
State/province [43] 0 0
Tel-Aviv
Country [44] 0 0
Italy
State/province [44] 0 0
Bergamo
Country [45] 0 0
Italy
State/province [45] 0 0
Catanzaro
Country [46] 0 0
Italy
State/province [46] 0 0
Napoli
Country [47] 0 0
Italy
State/province [47] 0 0
Padova
Country [48] 0 0
Italy
State/province [48] 0 0
Partinico
Country [49] 0 0
Italy
State/province [49] 0 0
Pisa
Country [50] 0 0
Italy
State/province [50] 0 0
Roma
Country [51] 0 0
Italy
State/province [51] 0 0
Torino
Country [52] 0 0
Kuwait
State/province [52] 0 0
Kuwait
Country [53] 0 0
Lebanon
State/province [53] 0 0
Beirut
Country [54] 0 0
Lebanon
State/province [54] 0 0
Hazmieh
Country [55] 0 0
Norway
State/province [55] 0 0
Oslo
Country [56] 0 0
Sweden
State/province [56] 0 0
Göteborg
Country [57] 0 0
Sweden
State/province [57] 0 0
Stockholm
Country [58] 0 0
Switzerland
State/province [58] 0 0
Genève
Country [59] 0 0
Switzerland
State/province [59] 0 0
Olten
Country [60] 0 0
Switzerland
State/province [60] 0 0
Reinach
Country [61] 0 0
Turkey
State/province [61] 0 0
Adana
Country [62] 0 0
Turkey
State/province [62] 0 0
Ankara
Country [63] 0 0
Turkey
State/province [63] 0 0
Corum
Country [64] 0 0
Turkey
State/province [64] 0 0
Hatay
Country [65] 0 0
Turkey
State/province [65] 0 0
Izmir
Country [66] 0 0
Turkey
State/province [66] 0 0
Kayseri
Country [67] 0 0
Turkey
State/province [67] 0 0
Samsun
Country [68] 0 0
United Arab Emirates
State/province [68] 0 0
Dubai
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Exeter
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Manchester
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Middlesborough
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Stevenage
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Torquay
Country [74] 0 0
United Kingdom
State/province [74] 0 0
West Bromwich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

To demonstrate the superiority of alirocumab in comparison with usual care in the reduction
of non-high-density lipoprotein cholesterol (non-HDL-C) in participants with type 2 diabetes
and mixed dyslipidemia at high cardiovascular risk with non-HDL-C not adequately controlled
with maximally tolerated statin therapy.

Secondary Objectives:

- To demonstrate whether alirocumab is superior in comparison with usual care in its
effects on other lipid parameters (ie, low-density lipoprotein cholesterol (LDL-C),
apolipoprotein B (Apo B), total cholesterol (Total -C), lipoprotein a (Lp[a]),
high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), triglyceride rich
lipoproteins (TGRLs), apolipoprotein A-1 (Apo A-1), apolipoprotein C-III (Apo C-III),
lipid subfractions by nuclear magnetic resonance (NMR) spectroscopy (ie, LDL-C particle
size and LDL, very low-density lipoprotein [VLDL], HDL, and intermediate-density
lipoprotein [IDL] particle number).

- To assess changes in glycemic parameters with alirocumab vs. usual care treatment.

- To demonstrate the safety and tolerability of alirocumab.

- To evaluate treatment acceptance of alirocumab.

- To evaluate proprotein convertase subtilisin kexin type 9 (PCSK9) concentrations and
antibody development.

- To demonstrate the superiority of alirocumab vs. fenofibrate on non-HDL-C and other
lipid parameters (subgroup analysis).
Trial website
https://clinicaltrials.gov/show/NCT02642159
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications