A Phase I, Randomized, Double-Blind, Placebo Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 986 in Healthy Subjects and Heart Failure Patients

Completed

• Conditions: Heart failure; cardiac insufficiency; 10019280

• Registration Number: NL-OMON46755
• Lead Sponsor: Amgen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 4

Inclusion Criteria

Criteria for HFrEF- Patients between the ages of 18 and 85 years with stable NYHA class
II or III chronic HF in sinus rhythm on optimal therapy and a left ventricular ejection
fraction of < 40% and NT-proBNP level of > 250 pg/mL.
* Criteria for HFpEF- Patients between the ages of 18 and 85 years with stable NYHA
class II or III chronic HF, in sinus rhythm on optimal standard of care therapy with a left
ventricular ejection fraction of > 50% and NT-proBNP level of > 250 pg/mL.

Exclusion Criteria

*Heart rate * 100 beats per minute after 5 minutes of rest or an untreated symptomatic bradyarrhythmia within 1 month prior to enrollment.
*Severe uncorrected valvular heart disease, or hypertrophic obstructive
cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically
significant congenital heart disease.
*Estimated glomerular filtration rate (eGFR)
within the screening period of less than 30 mL/min/1.732m2 as calculated using
the Modification of Diet in Renal Disease (MDRD) formula.
*For subjects in Part C of the study: Systolic blood pressure > 160 mm Hg or <
100 mm Hg, or diastolic blood pressure > 110 mm Hg or < 60 mm Hg, assessed
on 2 separate occasions prior to enrollment.
*For subjects in Part C of the study: Troponin I > ULN if there is also evidence of
an acute cardiovascular event.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Subject incidence of treatment-emergent adverse events.<br /><br>* Subject incidence of clinically significant changes in physical examinations,<br /><br>vital signs,<br /><br>laboratory safety tests, and electrocardiograms (ECGs).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>AMG 986 PK parameters including, but not limited to, maximum observed<br /><br>concentration<br /><br>(Cmax), the time of maximum observed concentration (tmax), area under the<br /><br>concentration-time curve (AUC), and oral bioavailability.<br /><br>* Changes over time from baseline in echocardiographic parameters of left<br /><br>ventricular<br /><br>systolic and diastolic functions (left ventricular ejection fraction, fraction<br /><br>shortening, stroke<br /><br>volume, wall thickening, end-systolic and end-diastolic volumes and indexes,<br /><br>septal and<br /><br>lateral e*, E/A ratio, E/e* ratio, E wave deceleration time, left atrial volume<br /><br>index) in<br /><br>heart failure patients, as well as changes in ventriculo-arterial coupling and<br /><br>global strain in heart failure patients </p><br>