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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Additional relevant MeSH terms:
Mipomersen
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Molecular Probes
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on August 20, 2014