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

This study has been completed.
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by:
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT01090661
First received: March 18, 2010
Last updated: July 16, 2010
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: mipomersen sodium
Drug: moxifloxacin hydrochloride (Avelox®)
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blinded Crossover Trial to Define the ECG Effects of Mipomersen (ISIS 301012) Using a Therapeutic and Supratherapeutic Dose Compared to Placebo and Moxifloxacin (a Positive Control) in Healthy Men and Women: A Thorough ECG Trial

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • change from baseline in QTcF (corrected Frederica's CT interval) [ Time Frame: ECG monitoring up to 24 hours post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ECG intervals (QTcB (corrected Bazett's QT interval), HR (heart rate, PR, QRS, and QT) [ Time Frame: ECG monitoring up to 24 hours post dose ] [ Designated as safety issue: No ]
  • change in ECG morphological patterns [ Time Frame: ECG monitoring up to 24 hours post dose ] [ Designated as safety issue: No ]
  • Correlation between delta delta QTc interval and plasma mipomersen concentrations [ Time Frame: ECG monitoring up to 24 hours post dose ] [ Designated as safety issue: No ]
  • Incidence of treatment-emergent Adverse Events [ Time Frame: Assessed at each visit ] [ Designated as safety issue: Yes ]
  • mipomersen plasma pharmacokinetic (PK) paramerts: Area Under the Curve (AUC 0-22.5h), Maximum Concentration (Cmax), Time to Maximum Concentration (Tmax) [ Time Frame: Serial PK sampling up to 24 hours post dose ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: March 2010
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: mipomersen IV (supra-therapeutic dose)
200 mg of mipomersen IV / placebo SC
Drug: mipomersen sodium
200 mg of mipomersen intravenous (IV) (single dose)
Other Name: ISIS 301012
Drug: placebo
placebo subcutaneous (SC) single dose
Experimental: mipomersen SC (therapeutic dose)
200 mg of mipomersen SC / placebo IV
Drug: mipomersen sodium
200 mg of mipomersen subcutaneous (SC) (single dose)
Other Name: ISIS 301012
Drug: placebo
placebo intravenous (IV) single dose
Active Comparator: moxifloxacin IV
400 mg of moxifloxacin IV / placebo SC
Drug: moxifloxacin hydrochloride (Avelox®)
400 mg of moxifloxacin intravenous (IV) single dose
Drug: placebo
placebo subcutaneous (SC) single dose
Placebo Comparator: placebo
Placebo IV / placebo SC
Drug: placebo
placebo intravenous (IV) single dose
Drug: placebo
placebo subcutaneous (SC) single 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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01090661

Locations
United States, Texas
PPD Development, LP
Austin, Texas, United States
Sponsors and Collaborators
Genzyme, a Sanofi Company
Isis Pharmaceuticals
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT01090661     History of Changes
Other Study ID Numbers: MIPO2800209
Study First Received: March 18, 2010
Last Updated: July 16, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Genzyme, a Sanofi Company:
antisense
ApoB (Apolipoprotein B)
LDL (low density lipoprotein)
thorough QT

Additional relevant MeSH terms:
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Mipomersen
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Molecular Probes
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on August 21, 2014