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

NCT01090661 | Completed Phase 1 DMC

• 1 other identifier: MIPO2800209
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

antisense; ApoB (Apolipoprotein B); LDL (low density lipoprotein); thorough QT

Outcome Measures

Primary Outcomes (1)

• change from baseline in QTcF (corrected Frederica's CT interval)

  ECG monitoring up to 24 hours post dose

Secondary Outcomes (5)

• ECG intervals (QTcB (corrected Bazett's QT interval), HR (heart rate, PR, QRS, and QT)

  ECG monitoring up to 24 hours post dose

• change in ECG morphological patterns

  ECG monitoring up to 24 hours post dose

• Correlation between delta delta QTc interval and plasma mipomersen concentrations

  ECG monitoring up to 24 hours post dose

• Incidence of treatment-emergent Adverse Events

  Assessed at each visit

• mipomersen plasma pharmacokinetic (PK) parameters: Area Under the Curve (AUC 0-22.5h), Maximum Concentration (Cmax), Time to Maximum Concentration (Tmax)

  Serial PK sampling up to 24 hours post dose

Study Arms (4)

mipomersen IV (supra-therapeutic dose)

EXPERIMENTAL

200 mg of mipomersen IV / placebo SC

Drug: mipomersen sodium; Drug: placebo

mipomersen SC (therapeutic dose)

EXPERIMENTAL

200 mg of mipomersen SC / placebo IV

Drug: mipomersen sodium; Drug: placebo

moxifloxacin IV

ACTIVE COMPARATOR

400 mg of moxifloxacin IV / placebo SC

Drug: moxifloxacin hydrochloride (Avelox®); Drug: placebo

placebo

PLACEBO COMPARATOR

Placebo IV / placebo SC

Drug: placebo

Interventions

mipomersen sodium DRUG

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

Also known as: ISIS 301012

mipomersen IV (supra-therapeutic dose)

moxifloxacin hydrochloride (Avelox®) DRUG

400 mg of moxifloxacin intravenous (IV) single dose

moxifloxacin IV

placebo DRUG

placebo intravenous (IV) single dose

mipomersen SC (therapeutic dose); placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

PPD Development, LP

Austin, Texas, United States

Location

MeSH Terms

Interventions

mipomersen; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2010
• First Posted: March 22, 2010
• Study Start: March 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: August 3, 2016

Record last verified: 2016-08

Locations

US (1)