A Study to Evaluate the Effect of Mipomersen on Cardiac Repolarization Conducted in Healthy Subjects

NCT ID: NCT01090661

Last Updated: 2016-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2010-05-31

Brief Summary

To assess the electrocardiogram (ECG) effects of mipomersen administered as a 200-mg subcutaneous (SC) therapeutic and a 200-mg intravenous (IV; [2-hour infusion]) supra-therapeutic dose relative to placebo in healthy adult male and female subjects; and to evaluate the safety and pharmacokinetics (PK) of mipomersen when administered as a single therapeutic (200 mg) SC and a single, supra-therapeutic (200 mg) IV dose.

Detailed Description

This will be a randomized, double-blind, single-site, crossover study in healthy male and female subjects to determine if mipomersen administered as a single therapeutic (200 mg) SC and a single supra-therapeutic (200 mg) IV dose delays cardiac repolarization as determined by the measurement of QT/corrected QT (QTc) interval. A total of 60 healthy male and female subjects will be enrolled in this 4-way crossover study, randomly assigned to 1 of 8 treatment sequences, and cross over into 4 treatment periods where each subject will receive both a single SC injection and a single IV infusion during each period.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

mipomersen IV (supra-therapeutic dose)

200 mg of mipomersen IV / placebo SC

Group Type: EXPERIMENTAL

mipomersen sodium

Intervention Type: DRUG

200 mg of mipomersen intravenous (IV) (single dose)

placebo

Intervention Type: DRUG

placebo subcutaneous (SC) single dose

mipomersen SC (therapeutic dose)

200 mg of mipomersen SC / placebo IV

Group Type: EXPERIMENTAL

mipomersen sodium

Intervention Type: DRUG

200 mg of mipomersen subcutaneous (SC) (single dose)

placebo

Intervention Type: DRUG

placebo intravenous (IV) single dose

moxifloxacin IV

400 mg of moxifloxacin IV / placebo SC

Group Type: ACTIVE_COMPARATOR

moxifloxacin hydrochloride (Avelox®)

Intervention Type: DRUG

400 mg of moxifloxacin intravenous (IV) single dose

placebo

Intervention Type: DRUG

placebo subcutaneous (SC) single dose

placebo

Placebo IV / placebo SC

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo intravenous (IV) single dose

placebo

Intervention Type: DRUG

placebo subcutaneous (SC) single dose

Interventions

mipomersen sodium

200 mg of mipomersen intravenous (IV) (single dose)

Intervention Type: DRUG

mipomersen sodium

200 mg of mipomersen subcutaneous (SC) (single dose)

Intervention Type: DRUG

moxifloxacin hydrochloride (Avelox®)

400 mg of moxifloxacin intravenous (IV) single dose

Intervention Type: DRUG

placebo

placebo intravenous (IV) single dose

Intervention Type: DRUG

placebo

placebo subcutaneous (SC) single dose

Intervention Type: DRUG

Other Intervention Names

ISIS 301012; ISIS 301012

Eligibility Criteria

Inclusion Criteria

• Written informed consent provided before any study-related procedures are performed.
• Body mass index (BMI) of 19 to 32 kg/m2 inclusive.
• Subjects can not have consumed nicotine or nicotine-containing products for at least 6 months before Screening.
• Subjects are nonpregnant and nonlactating, surgically sterile, postmenopausal, abstinent, or subject or partner is willing to use a reliable method of contraception during the study and 5 months after the last dose of investigational product.

Exclusion Criteria

• History of risk factors for Torsades de Pointes, known Long QT Syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments or family history of Long QT or Brugada Syndrome.
• Abnormal screening ECG that is interpreted by the Investigator to be clinically significant.
• Use of concomitant medications (prescribed or over-the-counter), without the approval of the Investigator and Sponsor, within 7 days before the first dose of investigational product.
• Clinically significant abnormal findings on the physical examination, ECG, blood pressure, heart rate, medical history, or clinical laboratory results at Screening or before dosing.
• History of clinically significant allergies or hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease.
• Positive test for HIV antibody, hepatitis C antibody, or hepatitis B surface antigen.
• Positive test for drugs of abuse, alcohol, or cotinine at Screening or before dosing or history of drug or alcohol abuse or dependence within 1 year before Screening.
• History of cancer, with the exception of basal cell carcinoma.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Kastle Therapeutics, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

PPD Development, LP

Austin, Texas, United States

Countries

United States

Other Identifiers

MIPO2800209

Identifier Type: -

Identifier Source: org_study_id