A Study Comparing Two Subcutaneous Formulations: Vial and Autoinjector (AI) With Olezarsen, at Two Dose Levels, in Healthy Adult Participants

Study Overview
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Brief Summary
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The purpose of the study is to assess the bioequivalence of olezarsen between 2 subcutaneous (SC) formulations [(autoinjector (AI) and vial] at 2 dose levels in healthy adult participants.

Detailed Description
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This is a Phase 1, single-dose, randomized, open-label, two-period, crossover study in approximately 100 healthy participants. The study will consist of an up to 28-day Screening Period, two treatment periods of 15 days each - with the second treatment period starting 28-42 days after the first begins - and a Post-Treatment Follow-Up Period lasting 91 days after the second treatment period begins. Eligible participants will be randomized to two dose groups (50 mg or 80 mg olezarsen). Participants will be dosed once at the beginning of each treatment period, one time using a single-use AI and one time using a single-use vial. Within each dose group, approximately half of the participants will be dosed with the AI first, with the other participants being dosed with the vial first.

Official Title
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A Single-Dose, Randomized, Open-Label, Two-Period Crossover, Bioequivalence Study Comparing Two Subcutaneous Formulations: Vial and Autoinjector (AI) With Olezarsen, at Two Dose Levels, in Healthy Adult Participants

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: Olezarsen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have given written informed consent (signed and dated) and any authorizations required by local law, be able to comply with all study requirements prior to receiving any study drug, and be able to communicate effectively with clinic staff Must be a healthy, adult male or female, 18 to 64 years of age (inclusive), and non-smoking (for at least 6 months prior to first study drug administration) Females must be of non-childbearing potential Exclusion Criteria: 1. Have a known history or presence of any clinically significant hepatic (e.g., hepatic impairment), renal/genitourinary (e.g., renal impairment), gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological, or hematological disease or condition unless determined as not clinically significant by the PI/sub-investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olezarsen Dose Level 1<br>Participants will receive two doses of Dose Level 1 each, using one of the following two sequences: (i) AI on Day 1 of Treatment Period 1, followed by vial on Day 1 of Treatment Period 2; or (ii) vial on Day 1 of Treatment Period 1, followed by AI on Day 1 of Treatment Period 2. A washout period of 28-42 days will be maintained between the 2 treatment periods. | Drug: Olezarsen<br>* Olezarsen will be administered by SC injection.<br>* Other names: ISIS 678354;|
| Experimental: Olezarsen Dose Level 2<br>Participants will receive two doses of Dose Level 2 each, using one of the following two sequences: (i) AI on Day 1 of Treatment Period 1, followed by vial on Day 1 of Treatment Period 2; or (ii) vial on Day 1 of Treatment Period 1, followed by AI on Day 1 of Treatment Period 2 A washout period of at least 28 days will be maintained between the 2 treatment periods. | Drug: Olezarsen<br>* Olezarsen will be administered by SC injection.<br>* Other names: ISIS 678354;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC) of olezarsen from time 0 to 336 hours (AUC0-336h) |  | Up to Day 8 of each of Treatment Periods 1 and 2 | 
| Maximum plasma concentration of olezarsen (Cmax) |  | Up to Day 91 of Treatment Period 2 |