A Study to Evaluate 3 Different Dosing Regimens of Mipomersen Administered Via Subcutaneous Injections to Healthy Volunteers

NCT01061814 | Completed Phase 1 DMC

• 1 other identifier: MIPO3200309
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for coronary heart disease (CHD). Mipomersen is an antisense drug that reduces a protein in the liver cells called apolipoprotein B-100 (apoB-100). ApoB-100 plays a role in producing low density lipoprotein cholesterol (LDL-C) (the 'bad' cholesterol) and moving it from the liver to one's bloodstream. High LDL-C is an independent risk factor for the development of coronary heart disease (CHD) or other diseases of blood vessels. It has been shown that lowering LDL-C reduces the risk of heart attacks and other major adverse cardiovascular events. Mipomersen is an investigational product being studied to determine if it is safe and effective in lowering LDL-C in specific populations of patients with hypercholesterolemia. This phase 1 study is being conducted to evaluate 3 different dosing regimens (daily, 3 times per week, or weekly) in healthy volunteers for a total of 3 weeks of dosing. Study procedures will include blood testing and physical examinations to assess the safety and tolerability of the different regimens. Tests will also be done to determine how much of the drug is present in the circulation (blood flow in the body). Specific pharmacokinetic (PK) tests on the blood samples will determine what the body does to the investigational product after it is injected, including how it is absorbed, distributed, the rate at which drug action begins and the duration of the effect. Eligible subjects will receive study injections of either mipomersen or placebo over a 3 week period followed by a 12 week safety follow-up period.

Conditions

Healthy Volunteer

Keywords

ApoB (Apolipoprotein B); LDL (low density lipoprotein); mipomersen; ISIS301012; antisense

Outcome Measures

Primary Outcomes (4)

• Incidence of treatment-emergent AEs and SAEs

  Assessed at each study visit through 21 weeks

• Maximum plasma concentration (Cmax)

  variable up to 105 days

• time to maximal concentration (Tmax)

  variable up to 105 days

• area under the curve (AUC) based on PK profiles following the first and last dose

  variable up to 105 days

Study Arms (2)

mipomersen

EXPERIMENTAL

30 mg (cohort A), 70mg (cohort B) or 200mg (cohort C) SC daily

Drug: mipomersen

Placebo

PLACEBO COMPARATOR

30 mg (cohort A), 70mg (cohort B), or 200mg (cohort C) SC daily

Drug: Placebo

Interventions

mipomersen DRUG

30 mg (cohort A), 70mg (cohort B) or 200mg (cohort C) subcutaneous (SC) dose of study drug daily for 3 weeks

Also known as: ISIS 301012

mipomersen

Placebo DRUG

30 mg (cohort A), 70mg (cohort B), or 200mg (cohort C) subcutaneous (SC) dose of study drug daily for 3 weeks

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:

• Age 18 to 75, inclusive
• On acceptable birth control and/or partner compliant with acceptable contraceptive for 4 weeks prior to, during, and 12 weeks after the last study drug dose.
• In good overall health
• Body weight \> 50 kg and body mass index (BMI) \< 32 kg/m2
• Skin Type I-III based on Fitzpatrick scale

You may not qualify if:

• Clinically significant (CS) abnormalities in medical history, physical examination or laboratory assessments
• Positive test for human immunodeficiency virus (HIV), hepatitis B or C.
• Malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for \> 1 year)
• History of rash, impetigo, or drug allergies
• Alcohol and/or drug abuse
• Receiving prescription medications within 30 days, with the exception of contraceptives; Vaccinations are not allowed beginning 3 weeks prior to the first dose of study drug until completion of the Day 28 visit

Sponsors & Collaborators

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

Study Sites (1)

Anapharm, Inc.

Montreal, Quebec, H3X 2H9, Canada

Location

Related Publications (1)

• Flaim JD, Grundy JS, Baker BF, McGowan MP, Kastelein JJ. Changes in mipomersen dosing regimen provide similar exposure with improved tolerability in randomized placebo-controlled study of healthy volunteers. J Am Heart Assoc. 2014 Mar 13;3(2):e000560. doi: 10.1161/JAHA.113.000560.

  PMID: 24627419 DERIVED

MeSH Terms

Interventions

mipomersen

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2010
• First Posted: February 3, 2010
• Study Start: January 1, 2010
• Primary Completion: March 1, 2010
• Study Completion: June 1, 2010
• Last Updated: August 3, 2016

Record last verified: 2016-08

Locations

CA (1)