Effect of Alirocumab on Postprandial Hyperlipemia in Patients With Type 2 Diabetes

NCT03344692 | Completed Phase 3

• 1 other identifier: RC16_0406
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged over the past decade as a post-transcriptional regulator of the LDL receptor (LDL-R). PCSK9 acts as an endogenous natural inhibitor of the LDL-R pathway. Monoclonal antibodies (mAb) directed against PCSK9, such as Alirocumab, are the most common method of PCSK9 inhibition. The goal of the present study is to assess, in the context of type 2 diabetes, a situation associated with an increased post-prandial hyperlipemia, whether PCSK9 inhibition with Alirocumab affects postprandial intestinal lipoprotein metabolism.

Conditions

Type2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Total area under the post-prandial triglycerides concentration-time curve from meal-time until 8h (AUC0-8h) after standardized high fat meal.

  Fifteenth days after the fifth injection of treatment (thus 10 weeks after first injection of treatment), subjects will be reported to investigational site (after a 12 hours overnight fast). Subjects must consume the test meal within 15 min. Upon completion of the meal (T0), sequential postprandial measurements of triglycerides concentrations will be taken. Blood samples will be collected at T-15, every 30 min for the first two hours after meal consumption, thereafter in 60 min intervals from T120 until 240 min and thereafter in 120 min intervals from T240 until 480 min.

  During 8 hours at week 10 after first treatment injection

Secondary Outcomes (3)

• Effect of treatment with alirocumab versus placebo following a standardized high-fat meal on post-prandial lipid metabolism (plasma lipoproteins, apolipoproteins, ...)

  During 8 hours at week 10 after first treatment injection

• Effect of treatment with alirocumab versus placebo on fasting lipid metabolism following a standardized high fat meal, using the same biomarkers than those used in the post-prandial state, plus indirect markers of cholesterol absorption and synthesis

  10 weeks after treatment first injection

• Effect of treatment with alirocumab versus placebo on fasting and post-prandial and glucose homeostasis following a standardized high-fat meal

  Before and during 8 hours after high fat meal at week 10 after first treatment injection

Study Arms (2)

Alirocumab

EXPERIMENTAL

Alirocumab 75 mg for subcutaneous injection via a pre-filled pen. One injection every 2 weeks during a 10-weeks period (5 injections in total)

Drug: Alirocumab

Placebo

PLACEBO COMPARATOR

Placebo matching alirocumab is prepared in the same formulation as alirocumab, without the addition of protein, for subcutaneous injection via a pre-filled pen. One injection every 2 weeks during a 10-weeks period (5 injections in total)

Other: Placebo

Interventions

Alirocumab DRUG

prefilled pen containing 75 mg of Praluent (Alirocumab) in 1 ml of solution

Alirocumab

Placebo OTHER

prefilled pen containing 1 ml of solution without Praluent

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men with type 2 diabetes diagnosed since ≥ 6 months
• HbA1C \<9.0%
• Men with primary hypercholesterolemia and/or mixed dyslipidemia
• Aged 18-75 years (limits inclusive)
• Metformin
• And/or Sulphonylureas (SUs)
• And/or Repaglinide
• And/or DPP-4 inhibitors
• And/or GLP1 receptor agonists: exenatide, liraglutide, dulaglutide
• Fasting serum TG ≥ 150 mg/dl and \< 500 mg/dl
• BMI: 20-45 kg/m2
• Use of statins or ezetimibe is allowed if treatment is stable for ≥ 1 month before the screening

You may not qualify if:

• Any secondary causes of hypercholesterolemia or of mixed dyslipidemia (nephrotic syndrome, hypothyroidism…)
• impaired liver function (AST and/or ALT ≥ 3ULN)
• impaired renal function (eGFR with CKD-EPI formula \< 30 ml/min)
• Alcohol abuse (\> 2 standard alcoholic drink per day; 1 standard alcoholic drink is the equivalent of 10g of alcohol)
• History of myocardial infarction, acute coronary syndrome, unstable angina pectoris, stroke, transient ischemic attack, or cardiac revascularization within the 6 months before the screening visit.
• History of PCSK9 mAb use
• Known sensitivity to monoclonal antibody therapeutics or to their excipients
• Lipid lowering therapies (other than statins), including fibrates, omega-3 fatty acids, bile acid sequestrants, niacin.
• Insulin-treated patients
• History of bariatric surgery
• Inflammatory bowel diseases and gastrointestinal malabsorption diseases
• Uncontrolled hypothyroidism (TSH \> ULN and Free T4 \< ULN) or hyperthyroidism (TSH \< ULN)
• Active cancer: progressive cancer or remission ≤ 3 years, except for basal or squamous cell carcinoma of the skin that has been successfully treated
• Known history of positive test for HIV, hepatitis C or chronic hepatitis B
• Corticosteroids therapy

Sponsors & Collaborators

• Nantes University Hospital: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

University Hospital of Nantes

Nantes, 44093, France

Location

MeSH Terms

Interventions

alirocumab

Study Officials

• Bertrand CARIOU

  Nantes University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 17, 2017
• Study Start: February 12, 2019
• Primary Completion: April 28, 2022
• Study Completion: April 28, 2022
• Last Updated: September 27, 2022

Record last verified: 2022-09

Locations

FR (1)