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

August 1, 2016 updated by: Kastle Therapeutics, LLC

A Prospective, Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Relative Bioavailability, Pharmacokinetics, Safety, and Tolerability of Daily, Thrice Weekly, and Weekly Dosing Regimens of Mipomersen Administered Subcutaneously to Healthy Volunteers

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, randomized, double blind placebo-controlled, parallel-group, single center Phase 1 study to investigate the relative bioavailability, PK, safety, and tolerability of different sc dosing regimens of mipomersen in healthy volunteers. The bioavailability of 2 test regimens (Cohorts A and B) will be assessed relative to that of the reference treatment regimen (Cohort C). Approximately 84 subjects will be randomized equally to 1 of the 3 treatment regimens and then further randomized in a 3:1 ratio to mipomersen vs. placebo:

Cohort A/Test Treatment Regimen 1: up to 28 subjects will receive a 30 mg sc dose of study drug or matching volume of placebo daily for 3 weeks (21 doses; 630 mg total) Cohort B/Test Treatment Regimen 2: up to 28 subjects will receive a 70 mg sc dose of study drug or matching volume of placebo 3 times a week for 3 weeks (9 doses; 630 mg total) Cohort C/Reference Treatment Regimen: up to 28 subjects will receive a 200 mg sc dose of study drug or matching volume of placebo once a week for 3 weeks (3 doses; 600 mg total) Each subject will participate in a ≤ 6-week screening period, a 3-week treatment period, and a 12-week safety follow-up period.

Study Type

Interventional

Enrollment (Actual)

84

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal,, Quebec, Canada, H3X 2H9
        • Anapharm, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: mipomersen
30 mg (cohort A), 70mg (cohort B) or 200mg (cohort C) SC daily
Drug: mipomersen
30 mg (cohort A), 70mg (cohort B) or 200mg (cohort C) subcutaneous (SC) dose of study drug daily for 3 weeks
Other Names:
  • ISIS 301012
PLACEBO_COMPARATOR: Placebo
30 mg (cohort A), 70mg (cohort B), or 200mg (cohort C) SC daily
Drug: Placebo
30 mg (cohort A), 70mg (cohort B), or 200mg (cohort C) subcutaneous (SC) dose of study drug daily for 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of treatment-emergent AEs and SAEs
Time Frame: Assessed at each study visit through 21 weeks
Assessed at each study visit through 21 weeks
Maximum plasma concentration (Cmax)
Time Frame: variable up to 105 days
variable up to 105 days
time to maximal concentration (Tmax)
Time Frame: variable up to 105 days
variable up to 105 days
area under the curve (AUC) based on PK profiles following the first and last dose
Time Frame: variable up to 105 days
variable up to 105 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kastle Therapeutics, LLC

Collaborators

Ionis Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (ACTUAL)

March 1, 2010

Study Completion (ACTUAL)

June 1, 2010

Study Registration Dates

First Submitted

January 8, 2010

First Submitted That Met QC Criteria

February 2, 2010

First Posted (ESTIMATE)

February 3, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

August 3, 2016

Last Update Submitted That Met QC Criteria

August 1, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MIPO3200309

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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