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

This study has been completed.
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by (Responsible Party):
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT01414881
First received: August 10, 2011
Last updated: February 4, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Healthy Volunteer
Drug: mipomersen
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Official Title: A Phase 1 Study to Assess the Effects of Mipomersen on Lipid and Lipoprotein Metabolism in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • Percent change in the production rate (PR) of very low density lipoprotein (VLDL) apolipoprotein B (apo B) [ Time Frame: through approximately 11 weeks of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Fractional clearance rate (FCR) of VLDL Triglyceride (TG), VLDL apo B, intermediate density lipoprotein (IDL) apo B, and low-density lipoprotein (LDL) apo B [ Time Frame: Through approximately 11 weeks of treatment ] [ Designated as safety issue: No ]
  • Production rate (PR) of VLDL-TG, IDL apo B, LDL apo B [ Time Frame: Through approximately 11 weeks of treatment ] [ Designated as safety issue: No ]
  • Conversion of VLDL apo B to low-density lipoprotein (LDL) apo B [ Time Frame: Through approximately 11 weeks of treatment ] [ Designated as safety issue: No ]
  • Direct removal of VLDL apo B from plasma [ Time Frame: Through approximately 11 weeks of treatment ] [ Designated as safety issue: No ]
  • Post-heparin hepatic lipase and lipoprotein lipase activities in serum [ Time Frame: Through approximately 11 weeks of treatment ] [ Designated as safety issue: No ]
  • Fasting plasma levels of fatty acids and beta-hydroxybutyrate [ Time Frame: Up to 40 weeks ] [ Designated as safety issue: No ]
  • Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 40 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: September 2011
Study Completion Date: November 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01414881

Locations
United States, New York
Columbia-Presbyterian Medical Center, MS Care Center
New York, New York, United States
Sponsors and Collaborators
Genzyme, a Sanofi Company
Isis Pharmaceuticals
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT01414881     History of Changes
Other Study ID Numbers: MIPO1600810
Study First Received: August 10, 2011
Last Updated: February 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Genzyme, a Sanofi Company:
ApoB (Apolipoprotein B)
LDL (low density lipoprotein)
mipomersen

ClinicalTrials.gov processed this record on April 16, 2014