A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Single Doses of Mipomersen in Japanese Healthy Volunteers

Study Overview
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Brief Summary
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This Phase 1 study is being conducted to evaluate 3 increasing subcutaneous (SC) doses (50, mg, 100 mg or 200mg) of mipomersen in Japanese healthy volunteers. Eligible subjects will receive a single study injection of either mipomersen or placebo. Subjects will be enrolled into 1 of 3 treatment cohorts (Cohorts A, B, and C) in a dose-escalation design. Dose-escalation will proceed only if there is an acceptable safety profile from the previous dosing level.

Official Title
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A Prospective, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Single Doses of Mipomersen Administered Subcutaneously to Japanese Healthy Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: mipomersen
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First generation Japanese (born in Japan of Japanese parents and Japanese grandparents), lived no more than 5 years outside of Japan, with no significant change in lifestyle or habits, including diet, while living outside of Japan. Surgically sterile, abstinent or subject or partner compliant with acceptable contraceptive during and 24 weeks after the last study drug dose Body weight >50 kg and body mass index between 18 and 30 kg/m2 inclusive Exclusion Criteria: Clinically significant cardiovascular, pulmonary, hepatic, renal, haematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, infectious, or psychiatric disease Clinically significant abnormal findings on the physical examination, ECG, blood pressure, heart rate, medical history, or clinical laboratory results at Screening or before dosing Positive test for human immunodeficiency virus (HIV), hepatitis B or C. High sensitivity C-reactive protein (hsCRP) >5 mg/L History of or current malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > 1 year) Evidence of acute or ongoing chronic inflammatory condition or infection History of rash, impetigo, or drug allergies Alcohol and/or drug abuse Smoking more than 10 cigarettes per day Planned dental work up to and including Day 8 procedures Treatment with another investigational drug, biological agent, or device within 4 weeks of Screening or 5 half-lives of the study agent, whichever is longer Use of prescribed medications within 4 weeks or over-the counter medications (including dietary supplements and herbal remedies) within 14 days before the first study drug dose, or use of any concomitant medications (prescribed or over the counter) through Day 8 of the study without Investigator and Sponsor approval. Vaccinations are not allowed beginning 3 weeks prior to the first dose of study drug until completion of the safety follow-up period Previous exposure to oligonucleotide-based drug therapy Donated 50 to 499 mL of blood within 30 days prior to consent, or >499 mL within 60 days

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mipomersen<br>50 mg (cohort A), 100mg (cohort B) or 200mg (cohort C) SC single dose | Drug: mipomersen<br>* 50 mg (cohort A), 100mg (cohort B) or 200mg (cohort C) subcutaneous (SC) single dose of study drug<br>* Other names: ISIS 301012;|
| Placebo Comparator: placebo<br>50 mg (cohort A), 100mg (cohort B) or 200mg (cohort C) SC single dose | Drug: placebo<br>* 50 mg (cohort A), 100mg (cohort B), or 200mg (cohort C) subcutaneous (SC) single dose of study drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | plasma PK parameters | Baseline up to Day 36 Post-Treatment | 
| Time to maximal concentration (Tmax) | plasma PK parameters | Baseline up to Day 36 Post-Treatment | 
| Area Under the Curve (AUC) | plasma PK parameters | Baseline up to Day 36 Post-Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Up to Day 36 Post-Treatment |