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

Healthy Volunteer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01414881
• Other study ID #: MIPO1600810
• Status: Completed
• Phase: Phase 1
• First received: August 10, 2011
• Last updated: August 1, 2016
• Start date: September 2011
• Est. completion date: November 2012

Study information

• Verified date: August 2016
• Source: Kastle Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject)

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• mipomersen
mipomersen 200mg subcutaneously (SC) once weekly
• Placebo
Placebo administered subcutaneously (SC) once weekly

Locations

Country	Name	City	State
United States	Columbia-Presbyterian Medical Center, MS Care Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Kastle Therapeutics, LLC	Ionis Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in the production rate (PR) of very low density lipoprotein (VLDL) apolipoprotein B (apo B)		through approximately 11 weeks of treatment	No
Secondary	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	No
Secondary	Production rate (PR) of VLDL-TG, IDL apo B, LDL apo B		Through approximately 11 weeks of treatment	No
Secondary	Conversion of VLDL apo B to low-density lipoprotein (LDL) apo B		Through approximately 11 weeks of treatment	No
Secondary	Direct removal of VLDL apo B from plasma		Through approximately 11 weeks of treatment	No
Secondary	Post-heparin hepatic lipase and lipoprotein lipase activities in serum		Through approximately 11 weeks of treatment	No
Secondary	Fasting plasma levels of fatty acids and beta-hydroxybutyrate		Up to 40 weeks	No
Secondary	Incidence of adverse events (AEs) and serious adverse events (SAEs)		Up to 40 weeks	Yes