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HypercholesterolemiaPhase 2NCT01288469

Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) When Co-administered With High Dose of Atorvastatin in Patients With Primary Hypercholesterolemia

A Phase 2 study testing Alirocumab and Atorvastatin in people with Hypercholesterolemia, run by Sanofi at 20 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Primary Objective: To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels compared with placebo when co-administered with 80 mg of atorvastatin after 8 weeks of treatment in participants with LDL-C ≥ 100mg/dL (≥ 2.59 mmol/L) on atorvastatin 10 mg. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hypercholesterolemia
What is being tested?
Alirocumab and Atorvastatin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
92 participants
Where
20 sitesUnited States
Study dates
Jan 2011to Sep 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants receiving a lipid-lowering treatment other than atorvastatin/ or not at stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening, or drug naive participants with primary hypercholesterolemia if they are likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the end of the 6-week run-in treatment period on atorvastatin therapy
  • OR
  • Participants with primary hypercholesterolemia treated with stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening and likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the screening visit.

Who cannot join

  • LDL-C < 100 mg/dL (< 2.59 mmol/L) at Week -1 (V1):
  • After the run-in period on atorvastatin 10 mg for participants receiving a lipid lowering treatment other than atorvastatin/ or not at stable dose of atorvastatin 10 mg for at least 6 weeks prior to the screening period, or drug naive participants.
  • OR
  • At the first visit for participants who are being treated with atorvastatin 10 mg at stable dose for at least 6 weeks prior to screening visit.
  • Participants not previously instructed on a cholesterol-lowering diet.
  • Participants with type 1 diabetes.
Show all 14Show fewer
  • Participants with type 2 diabetes treated with insulin.
  • Participants with type 2 diabetes and with an HbA1c ≥ 8.5% at screening visit (considered poorly controlled).
  • Laboratory findings measured before randomization:
  • Triglycerides (TG) > 350 mg/dL (> 3.95 mmol/L) at screening visit.
  • Positive serum or urine pregnancy test in females of childbearing potential.
  • Pregnant or breast-feeding women.
  • Women of childbearing potential with no effective contraceptive method.
  • The above information is not intended to contain all considerations relevant to a Participant's potential participation in a clinical trial.

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

United States20 sites
  • Investigational Site Number 840605

    Chicago, Illinois, 60610

  • Investigational Site Number 840619

    Chicago, Illinois, 60610

  • Investigational Site Number 840615

    Cincinnati, Ohio, 45219

  • Investigational Site Number 840617

    Cincinnati, Ohio, 45219

  • Investigational Site Number 840603

    Doral, Florida, 33166

  • Investigational Site Number 840604

    Edison, New Jersey, 08817

  • Investigational Site Number 840602

    Eugene, Oregon, 97404

  • Investigational Site Number 840611

    Jacksonville, Florida, 32223

  • Investigational Site Number 840618

    Jupiter, Florida, 33458

  • Investigational Site Number 840610

    Los Angeles, California, 90057

  • Investigational Site Number 840616

    Mesa, Arizona, 85206

  • Investigational Site Number 840612

    Miami, Florida, 33138

  • Investigational Site Number 840614

    Miami, Florida, 33138

  • Investigational Site Number 840608

    Newport Beach, California, 92660

  • Investigational Site Number 840609

    Olympia, Washington, 98502

  • Investigational Site Number 840613

    Oregon, Wisconsin, 53575

  • Investigational Site Number 840621

    Richmond, Virginia, 23227

  • Investigational Site Number 840606

    Rochester, New York, 14609

  • Investigational Site Number 840607

    St. Petersburg, Florida, 33609

  • Investigational Site Number 840601

    Tucson, Arizona, 85710

Other trials in United States

About this study

Official title: A Randomized, Double-blind, Parallel-group, Placebo-controlled, Fixed Dose/Dose Regimen, Multicenter Study Evaluating the Efficacy and Safety of SAR236553 When Co-administered With 80 mg of Atorvastatin Over 8 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥ 100 mg/dL (≥2.59 mmol/L) on Atorvastatin 10 mg

Primary Objective:

To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels compared with placebo when co-administered with 80 mg of atorvastatin after 8 weeks of treatment in participants with LDL-C ≥ 100mg/dL (≥ 2.59 mmol/L) on atorvastatin 10 mg.

Read more

Secondary Objectives:

  • To evaluate the effects of alirocumab on other lipid levels in comparison with placebo, when co-administered with 80 mg of atorvastatin after 8 weeks of treatment.
  • To evaluate the efficacy of alirocumab when co-administered with a high dose of atorvastatin (80 mg) versus atorvastatin 10 mg.
  • To evaluate the safety and tolerability of alirocumab when co-administered with 2 different doses of atorvastatin.
  • To evaluate the development of anti-alirocumab antibodies.
  • To evaluate the pharmacokinetics of alirocumab.
Read the detailed description

The duration of study participation depended on the status of the patient at screening:

  • For participants receiving atorvastatin 10 mg at stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 17 weeks including a screening period of 1 week, a double-blind treatment period of 8 weeks and a follow-up period of 8 weeks.
  • For participants receiving a lipid lowering treatment other than atorvastatin/ or not at stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 23 weeks with a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg of 6 weeks, a double-blind treatment period of 8 weeks and a follow-up period of 8 weeks.
Being tested
Alirocumab, Placebo (for alirocumab), Atorvastatin, Placebo (for atorvastatin)
Keywords
10020603
Medical subject headings
Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlirocumabDrug

    Also called SAR236553, REGN727

    One subcutaneous (SC) injection in the abdomen only.

  • Placebo (for alirocumab)Drug

    One SC injection in the abdomen only.

  • AtorvastatinDrug

    Over-encapsulated tablet orally once daily in the evening with dinner.

  • Placebo (for atorvastatin)Drug

    One over-encapsulated tablet of placebo for atorvastatin orally once daily in the evening with dinner.

Study groups in NCT01288469
Study groupRoleWhat they receive
Placebo + Atorvastatin 80 mgPlacebo comparatorPlacebo (for alirocumab) subcutaneous (SC) administration every 2 weeks (Q2W) in combination with atorvastatin 80 mg orally once daily for 8 weeks.
Receives: Drug: Placebo (for alirocumab); Drug: Atorvastatin
Alirocumab + Atorvastatin 10 mgExperimentalAlirocumab 150 mg SC administration Q2W in combination with atorvastatin 10 mg orally once daily for 8 weeks.
Receives: Drug: Alirocumab; Drug: Atorvastatin; Drug: Placebo (for atorvastatin)
Alirocumab + Atorvastatin 80 mgExperimentalAlirocumab 150 mg SC administration Q2W in combination with atorvastatin 80 mg orally once daily for 8 weeks.
Receives: Drug: Alirocumab; Drug: Atorvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change From Baseline in Calculated LDL-C at Week 8 - On-treatment Analysis

    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 8 data were imputed by last observation carried forward [LOCF] method.

    Measured: From Baseline to Week 8 (LOCF)

Secondary outcomes (6)
  1. Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 8 - On-treatment Analysis

    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

    Measured: From baseline to Week 8 (LOCF)

  2. Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 8 - On-treatment Analysis

    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

    Measured: From baseline to Week 8 (LOCF)

  3. Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and < 70 mg/dL (1.81 mmol/L) at Week 8 - On-treatment Analysis

    Measured: Week 8 (LOCF)

  4. Percent Change From Baseline in Total Cholesterol, Fasting Triglycerides, Non-high-Density Lipoprotein Cholesterol (Non-HDL-C), Apolipoprotein B (Apo-B) and Lipoprotein(a) at Week 8 - On-treatment Analysis

    Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (interquartile range).

    Measured: From baseline to Week 8 (LOCF)

  5. Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 8 - On-treatment Analysis

    Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

    Measured: From Baseline to Week 8 (LOCF)

  6. Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 8 - On-treatment Analysis

    Adjusted LS means and standard errors were estimated using the same ANCOVA as for primary endpoint.

    Measured: From Baseline to Week 8 (LOCF)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2011 (estimated)
  2. Study startJan 2011
  3. Primary completionSep 2011
  4. Study completionSep 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
92 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01288469
Sponsor's protocol ID
DFI11566
Other IDs
U1111-1117-9994
Status last verified
Jan 2015
First submitted
1 Feb 2011
Last updated
24 Sep 2015
Data monitoring committee
Yes

Publications

  • Roth EM, McKenney JM, Hanotin C, Asset G, Stein EA. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med. 2012 Nov 15;367(20):1891-900. doi: 10.1056/NEJMoa1201832. Epub 2012 Oct 31.

    PubMed 23113833
  • Gaudet D, Kereiakes DJ, McKenney JM, Roth EM, Hanotin C, Gipe D, Du Y, Ferrand AC, Ginsberg HN, Stein EA. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials). Am J Cardiol. 2014 Sep 1;114(5):711-5. doi: 10.1016/j.amjcard.2014.05.060. Epub 2014 Jun 18.

    PubMed 25060413
  • Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.

    PubMed 30183102
  • Toth PP, Hamon SC, Jones SR, Martin SS, Joshi PH, Kulkarni KR, Banerjee P, Hanotin C, Roth EM, McKenney JM. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo. Lipids Health Dis. 2016 Feb 13;15:28. doi: 10.1186/s12944-016-0197-4.

    PubMed 26872608

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alirocumab and Atorvastatin in people with Hypercholesterolemia, run by Sanofi at 20 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Calculated LDL-C at Week 8 - On-treatment Analysis (time frame: From Baseline to Week 8 (LOCF)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01288469, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2015.

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