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

Kastle Therapeutics

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: placebo; Drug: mipomersen sodium; Drug: moxifloxacin hydrochloride (Avelox®)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01090661

MIPO2800209

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

60 participants in 4 patient groups, including a placebo group

mipomersen IV (supra-therapeutic dose)

Experimental group

Description:

200 mg of mipomersen IV / placebo SC

Treatment:

Drug: placebo

Drug: placebo

Drug: mipomersen sodium

Drug: mipomersen sodium

mipomersen SC (therapeutic dose)

Experimental group

Description:

200 mg of mipomersen SC / placebo IV

Treatment:

Drug: placebo

Drug: placebo

Drug: mipomersen sodium

Drug: mipomersen sodium

moxifloxacin IV

Active Comparator group

Description:

400 mg of moxifloxacin IV / placebo SC

Treatment:

Drug: placebo

Drug: placebo

Drug: moxifloxacin hydrochloride (Avelox®)

placebo

Placebo Comparator group

Description:

Placebo IV / placebo SC

Treatment:

Drug: placebo

Drug: placebo