AMG 529 First in Human Study

Phase 1

Completed

Conditions: Cardiovascular

Interventions: Drug: AMG 529
Drug: Placebo

Registration Number: NCT03170193

Lead Sponsor: Amgen

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AMG 529	AMG 529	Participants received a single dose of AMG 529 at ascending dose levels by either subcutaneous or intravenous injection.
Placebo	Placebo	Participants received a single dose of placebo matching to AMG 529 by either subcutaneous or intravenous injection.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs)	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.	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Blood Alkaline Phosphatase Concentration Over Time	Baseline and days 3, 8, and 30
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.
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.
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 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.
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.
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.