Study to Assess the Effects of Mipomersen on Lipid and Lipoprotein Metabolism in Healthy Subjects

Study Overview
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Brief Summary
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The primary objective of this Phase I exploratory study is to determine the effects of mipomersen on the hepatic production of apolipoprotein-B (apo B) in very low density lipoprotein (VLDL) compared to baseline levels. The study will consist of a Screening Period, a 1-week Run-in Period to establish a stable diet, an approximate 11-week Treatment Period with Placebo or Mipomersen, and a 25-week Post-Treatment Follow-up Period. The total duration of any given subject's participation will be approximately 40 weeks.

Official Title
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A Phase 1 Study to Assess the Effects of Mipomersen on Lipid and Lipoprotein Metabolism in Healthy Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: mipomersen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-pregnant, non-lactating, surgically sterile, postmenopausal, abstinent, or the subject or partner is compliant with an acceptable contraceptive regimen for 4 weeks prior to Screening and willing to remain compliant with the contraceptive regimen throughout treatment and for 25 weeks after the last investigational product dose Body weight >50 kg, body mass index (BMI) ≤38 kg/m2, and stable weight (i.e., within 5% of mean body weight) for > 8 weeks prior to Screening Fasting TG levels of ≤170 mg/dL, fasting serum blood glucose of ≤115 mg/dL, and an HbA1c ≤6.5% Exclusion Criteria: Presence of any clinically significant abnormal laboratory profiles, physical exams, vital signs, or ECGs History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, infectious, or psychiatric disease Malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for >1 year) at Screening History of relevant food and/or drug allergies (i.e., allergy to heparin or any significant food allergy that could preclude a stable diet) The subject is receiving prescription lipid-lowering therapies such as statins, bile acid sequestrants, niacin/nicotinic acid, and/or fibrates or over-the-counter (OTC) fish oils, flaxseed, red rice or nutrient supplements that might affect lipid levels The subject is unwilling to limit alcohol consumption for the entire duration of the study The subject smokes >5 cigarettes per day

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mipomersen<br>mipomersen 200mg subcutaneously (SC) once weekly | Drug: mipomersen<br>* mipomersen 200mg subcutaneously (SC) once weekly<br>|
| Placebo Comparator: Placebo<br>Placebo administered subcutaneously (SC) once weekly | Drug: Placebo<br>* Placebo administered subcutaneously (SC) once weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in the production rate (PR) of very low density lipoprotein (VLDL) apolipoprotein B (apo B) |  | through approximately 11 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional clearance rate (FCR) of VLDL Triglyceride (TG), VLDL apo B, intermediate density lipoprotein (IDL) apo B, and low-density lipoprotein (LDL) apo B |  | Through approximately 11 weeks of treatment | 
| Production rate (PR) of VLDL-TG, IDL apo B, LDL apo B |  | Through approximately 11 weeks of treatment | 
| Conversion of VLDL apo B to low-density lipoprotein (LDL) apo B |  | Through approximately 11 weeks of treatment | 
| Direct removal of VLDL apo B from plasma |  | Through approximately 11 weeks of treatment | 
| Post-heparin hepatic lipase and lipoprotein lipase activities in serum |  | Through approximately 11 weeks of treatment | 
| Fasting plasma levels of fatty acids and beta-hydroxybutyrate |  | Up to 40 weeks | 
| Incidence of adverse events (AEs) and serious adverse events (SAEs) |  | Up to 40 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ApoB (Apolipoprotein B), LDL (low density lipoprotein), mipomersen