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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01090661
Recruitment Status : Completed
First Posted : March 22, 2010
Last Update Posted : August 3, 2016
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Kastle Therapeutics, LLC

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.

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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : March 2010
Actual Primary Completion Date : May 2010
Actual Study Completion Date : May 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. change from baseline in QTcF (corrected Frederica's CT interval) [ Time Frame: ECG monitoring up to 24 hours post dose ]

Secondary Outcome Measures :
  1. 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 ]
  2. change in ECG morphological patterns [ Time Frame: ECG monitoring up to 24 hours post dose ]
  3. Correlation between delta delta QTc interval and plasma mipomersen concentrations [ Time Frame: ECG monitoring up to 24 hours post dose ]
  4. Incidence of treatment-emergent Adverse Events [ Time Frame: Assessed at each visit ]
  5. mipomersen plasma pharmacokinetic (PK) parameters: 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01090661

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United States, Texas
PPD Development, LP
Austin, Texas, United States
Sponsors and Collaborators
Kastle Therapeutics, LLC
Ionis Pharmaceuticals, Inc.
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Study Director: Medical Monitor Genzyme, a Sanofi Company

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Responsible Party: Kastle Therapeutics, LLC Identifier: NCT01090661    
Other Study ID Numbers: MIPO2800209
First Posted: March 22, 2010    Key Record Dates
Last Update Posted: August 3, 2016
Last Verified: August 2016
Keywords provided by Kastle Therapeutics, LLC:
ApoB (Apolipoprotein B)
LDL (low density lipoprotein)
thorough QT
Additional relevant MeSH terms:
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Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
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
Lipid Regulating Agents