Clinical trial NCT01414881: Study to Assess the Effects of Mipomersen on Lipid and Lipoprotein Metabolism in Healthy Subjects
Official title: A Phase 1 Study to Assess the Effects of Mipomersen on Lipid and Lipoprotein Metabolism in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: ApoB (Apolipoprotein B)
LDL (low density lipoprotein)
mipomersen
Lead sponsor: Kastle Therapeutics, LLC
Sponsor class: INDUSTRY
Collaborators: name: Ionis Pharmaceuticals, Inc.
First posted: 2011-08-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent change in the production rate (PR) of very low density lipoprotein (VLDL) apolipoprotein B (apo B)
timeFrame: through approximately 11 weeks of treatment
Secondary outcomes:
measure: Fractional clearance rate (FCR) of VLDL Triglyceride (TG), VLDL apo B, intermediate density lipoprotein (IDL) apo B, and low-density lipoprotein (LDL) apo B
timeFrame: Through approximately 11 weeks of treatment
measure: Production rate (PR) of VLDL-TG, IDL apo B, LDL apo B
timeFrame: Through approximately 11 weeks of treatment
measure: Conversion of VLDL apo B to low-density lipoprotein (LDL) apo B
timeFrame: Through approximately 11 weeks of treatment
measure: Direct removal of VLDL apo B from plasma
timeFrame: Through approximately 11 weeks of treatment
measure: Post-heparin hepatic lipase and lipoprotein lipase activities in serum
timeFrame: Through approximately 11 weeks of treatment
measure: Fasting plasma levels of fatty acids and beta-hydroxybutyrate
timeFrame: Up to 40 weeks
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to 40 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia-Presbyterian Medical Center, MS Care Center
state: New York
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: