AMG 529 First in Human Study

Study Overview
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Brief Summary
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A study to assess the safety and tolerability of AMG 529 following single, ascending doses administered subcutaneously (SC) or intravenously (IV) in healthy adults.

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Ascending Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 529 in Healthy Subjects

Conditions
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Cardiovascular

Intervention / Treatment
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* Drug: AMG 529
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women ≥ 18 to ≤ 55 years old with no history or evidence of clinically relevant medical disorders Body mass index (BMI) between 18 and 32 kg/m², inclusive, at screening Women must be of non-reproductive potential as defined in protocol Other inclusion criteria may apply Exclusion Criteria: Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives (whichever is longer), since ending treatment on another investigational device or drug study(s) prior to receiving the first dose of investigational product Women who are lactating/breastfeeding or who plan to breastfeed while on study through 90 days after receiving the dose of investigational product Men with partners who are pregnant or planning to become pregnant while the subject is on study through 90 days after receiving the dose of investigational product Positive pregnancy test at screening or day -1 Other exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Within each dose cohort participants were randomized in a 3:1 ratio to receive either AMG 529 or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 529<br>Participants received a single dose of AMG 529 at ascending dose levels by either subcutaneous or intravenous injection. | Drug: AMG 529<br>* Ascending single doses of AMG 529 by subcutaneous (SC) or intravenous (IV) injection<br>|
| Placebo Comparator: Placebo<br>Participants received a single dose of placebo matching to AMG 529 by either subcutaneous or intravenous injection. | Drug: Placebo<br>* Single doses of matching placebo by SC or IV injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | Determination of the severity of adverse events was according to the following: grade 1 = mild (eg, asymptomatic or mild symptoms); grade 2 = moderate (eg, minimal intervention indicated or interferes with activity); grade 3 = severe (eg, medically significant but not immediately life-threatening, prevents daily activity, or requires treatment); grade 4 = life-threatening (ie, refers to an event in which the participant was, in the view of the investigator, at risk of death at the time of the event); and grade 5 = fatal. A serious adverse event was defined as an adverse event that met at least 1 of the following criteria: fatal life threatening required in patient hospitalization or prolongation of existing hospitalization resulted in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event. | From first dose up to 30 days for participants assigned to the 21 mg or 70 mg dose cohorts and up to 57 days for participants assigned to the 210 mg, 420 mg, or 700 mg dose cohorts. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) of AMG 529 |  | Predose and at 0.5 and 1 hour postdose (IV cohort only) and 6, 12, 24, 36, 48, 72, 120, 168, 240, 366, 504, and 696 hours postdose (all participants) and additionally at days 43 and 57 for participants assigned to the 210, 420, or 700 mg dose cohorts. | 
| Time to Maximum Observed Concentration (Tmax) of AMG 529 |  | Predose and at 0.5 and 1 hour postdose (IV cohort only) and 6, 12, 24, 36, 48, 72, 120, 168, 240, 366, 504, and 696 hours postdose (all participants) and additionally at days 43 and 57 for participants assigned to the 210, 420, or 700 mg dose cohorts. | 
| Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast) for AMG 529 |  | Predose and at 0.5 and 1 hour postdose (IV cohort only) and 6, 12, 24, 36, 48, 72, 120, 168, 240, 366, 504, and 696 hours postdose (all participants) and additionally at days 43 and 57 for participants assigned to the 210, 420, or 700 mg dose cohorts. | 
| Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time |  | Baseline and days 3, 8, and 30 | 
| Change From Baseline in Total Cholesterol Concentration Over Time |  | Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts. | 
| Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) Concentration Over Time |  | Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts. | 
| Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) Concentration Over Time |  | Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts. | 
| Change From Baseline in Triglycerides Concentration Over Time |  | Baseline and days 3, 6, 11, 22, 30 (all participants), and day 57 for participants assigned to the 210 mg, 420 mg, or 700 mg cohorts. |