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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: mipomersen; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States
      • Columbia-Presbyterian Medical Center, MS Care Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mipomersen; mipomersen 200mg subcutaneously (SC) once weekly	Drug: mipomersen; mipomersen 200mg subcutaneously (SC) once weekly
Placebo Comparator: Placebo; Placebo administered subcutaneously (SC) once weekly	Drug: Placebo; Placebo administered subcutaneously (SC) once weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Kastle Therapeutics, LLC
• Collaborators: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: August 10, 2011
• First Submitted That Met QC Criteria: August 10, 2011
• First Posted (Estimate): August 11, 2011

Study Record Updates

• Last Update Posted (Estimate): August 3, 2016
• Last Update Submitted That Met QC Criteria: August 1, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: ApoB (Apolipoprotein B); LDL (low density lipoprotein); mipomersen
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Mipomersen
• Other Study ID Numbers: MIPO1600810