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

NCT01414881 | Completed Phase 1

• 1 other identifier: MIPO1600810
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteer

Keywords

ApoB (Apolipoprotein B); LDL (low density lipoprotein); mipomersen

Outcome Measures

Primary Outcomes (1)

• Percent change in the production rate (PR) of very low density lipoprotein (VLDL) apolipoprotein B (apo B)

  through approximately 11 weeks of treatment

Secondary Outcomes (7)

• 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

Study Arms (2)

mipomersen

EXPERIMENTAL

mipomersen 200mg subcutaneously (SC) once weekly

Drug: mipomersen

Placebo

PLACEBO COMPARATOR

Placebo administered subcutaneously (SC) once weekly

Drug: Placebo

Interventions

mipomersen DRUG

mipomersen 200mg subcutaneously (SC) once weekly

mipomersen

Placebo DRUG

Placebo administered subcutaneously (SC) once weekly

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Kastle Therapeutics, LLC: lead
• Ionis Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Columbia-Presbyterian Medical Center, MS Care Center

New York, New York, United States

Location

MeSH Terms

Interventions

mipomersen

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2011
• First Posted: August 11, 2011
• Study Start: September 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: November 1, 2012
• Last Updated: August 3, 2016

Record last verified: 2016-08

Locations

US (1)