Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)

Study Overview
=================
Brief Summary
-----------------
This is a first-in-human, randomized, double-blind, placebo-controlled, single ascending dose study in subjects with elevated plasma Lipoprotein(a) [Lp(a)]. AMG 890 will be evaluated in approximately 80 subjects to assess safety, tolerability, pharmacokinetics and pharmacodynamic effects.

Official Title
-----------------
A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)

Conditions
-----------------
Cardiovascular Disease

Intervention / Treatment
-----------------
* Drug: AMG 890
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women with ages between 18 and 70 years old, inclusive. Protocol-defined elevated plasma Lp(a) level. Body mass index (BMI) greater than or equal to 18 and less than or equal to 40 kg/m2, at screening. Women must be of non-reproductive potential. Other Inclusion criteria may apply Exclusion Criteria: Currently receiving treatment in another investigational device or drug study. Women who are lactating/breastfeeding or who plan to breastfeed while on study or through 90 days after receiving the last dose of investigational product (for subjects who withdraw prior to end of study). History or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. History or clinical evidence of bleeding diathesis or any coagulation disorder. History or clinical evidence of peripheral neuropathy. Other Exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Single Ascending Dose Cohorts | Drug: Placebo<br>* Calculated volume to match experimental drug.<br>|
| Experimental: AMG 890<br>Single Ascending Dose Cohorts | Drug: AMG 890<br>* Ascending Single Doses of AMG 890<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject incidence of treatment-emergent adverse events |  | up to 365 days | 
| Changes in blood pressure | The analysis will include summary statistics at selected time points by treatment group. | Up to 365 days | 
| Changes in heart rate | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in respiratory rate | The analysis will include summary statistics at selected time points by treatment group. | Up to 365 days | 
| Changes in temperature | The analysis will include summary statistics at selected time points by treatment group. | Up to 365 days | 
| Changes in QRS interval | The analysis will include summary statistics at selected time points by treatment group. | Up to 365 days | 
| Changes in PR interval | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in QT interval | The analysis will include summary statistics at selected time points by treatment group. | Up to 365 days | 
| Changes in RR interval | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in red blood cells | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in platelets | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in white blood cells | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in prothrombin time (PT) |  | Up to 365 days | 
| Changes in international normalized ratio (INR) |  | Up to 365 days | 
| Changes in activated partial thromboplastin time (aPTT) |  | Up to 365 days | 
| Changes in Thrombin time (TT) |  | Up to 365 days | 
| Changes in aspartate aminotransferase (AST) levels (units: U/L) | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in alanine aminotransferase (ALT) levels (units: U/L) | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in total bilirubin levels (units: μmol/L) | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in direct bilirubin levels (units: μmol/L) | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in alkaline phosphatase levels (units: U/L) | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in total protein levels (units: g/L) | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 
| Changes in albumin levels (units: g/L) | The analysis will include summary statistics at selected time points by treatment group | Up to 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics parameter of maximum observed concentration (Cmax) |  | up to 365 days | 
| Pharmacokinetics parameter of time of maximum observed concentration (tmax) |  | up to 365 days | 
| Pharmacokinetics parameter of area under the concentration time curve (AUC) |  | up to 365 days | 
| Change in plasma Lp(a) over time |  | Up to 365 days | 
| Percent change in plasma Lp(a) over time |  | Up to 365 days |