Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 986 Administered Orally to Healthy Volunteers and Participants With Severely Impaired Renal Function

A Phase 1, Open-label, Single-dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 986 Administered Orally to Healthy Volunteers and Subjects With Severely Impaired Renal Function

A study to assess the safety, tolerability, and pharmacokinetics of AMG 986 given orally as a single dose to healthy participants and participants with severely impaired kidney function.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: AMG 986

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Tustin, California, United States, 92780
      • Research Site
  • Florida
    • Orlando, Florida, United States, 32809
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78215
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects, who are > or = 18 and < or = 65 years of age at the time of screening
• Subject has provided informed consent prior to initiation of any study-specific activities/procedures
• Women must be of non-reproductive potential (ie, postmenopausal, history of hysterectomy, or history of bilateral oophorectomy)
• Men must agree to practice an acceptable method of effective birth control while on study through 11 weeks after receiving the dose of study drug.
• Men must be willing to abstain from sperm donation while on study through 11 weeks after receiving the dose of study drug
• Body Mass Index > or = 18 and < or = 38 kg/m^2 at screening
• Physical examination and 12-lead electrocardiograms (ECGs) are clinically acceptable to the investigator
• Non-hypertensive subjects or subjects with treated, stable hypertension as defined by blood pressure not exceeding 170/100 mm Hg as an average during screening and day -1; for subjects with renal impairment, no change in dosage and medication for > or = 4 weeks prior to screening, and expected to remain on this dose and medication for the entire duration of the study
• Willing to maintain current general diet and physical activity regimen
• Renal function in 1 of the following 2 categories at the time of screening: Group 1 - Severe Renal Impairment (eGFR 15 to 29 mg/min/1.73 m^2) and not anticipated to require hemodialysis or renal transplantation, and anticipated to have renal function appropriate to severe renal impairment for the duration of the study OR Group 2 - Normal renal function (eGFR > or = 90 mg/min/1.73 m^2)

Exclusion Criteria:

• Subjects whose second modification of diet in renal disease (MDRD) eGFR result on day -1 is not within 15% of the first eGFR result performed during the screening period. Healthy volunteers who have normal renal function, but show a difference greater than 15% in eGFR based on MDRD during the screening period, will be included in the trial at the discretion of the investigator and the sponsor after a 24-hour creatinine clearance has been performed that meets eligibility criteria.
• Subjects who are the recipient of a renal transplant and/or are on immunosupressants.
• Subjects with a history of hospitalization for heart disease or angina within 4 months of screening.
• Current or prior malignancy within 5 years of enrollment with the exception of non-melanoma skin cancers, cervical or breast ductal carcinoma in situ, and adenocarcinoma of the prostate Stage I or IIa (defined as T1, T2a or T2b, N0-, M0 with documented serum prostate-specific antigen (PSA) < 20 ng/mL and Gleason score ≤ 7) per the American Joint Committee on Cancer (AJCC) primary tumor, regional lymph nodes, and distant metastasis system.
• Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (HepCAb) at screening
• History or evidence of any other clinically significant disorder, condition or disease with the exception of those outlined above that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
• Subject previously has entered this study or has been previously exposed to AMG 986.
• Heart rate ≥ 100 beats per minute after 5 minutes of rest or an untreated symptomatic bradyarrhythmia within 1 month prior to enrollment.
• Known history of drug or alcohol abuse within last 12 months.
• 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 dose of investigational product (AMG 986).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Severely Renal Impaired Participants; Participants with severely impaired renal function (estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m^2) receive a single oral dose of 200 mg AMG 986.	Drug: AMG 986; tablets for oral administration
Active Comparator: Group 2: Healthy Participants; Participants with normal renal function (eGFR >= 90 mL/min/1.73 m^2 or above) receive a single oral dose of 200 mg AMG 986.	Drug: AMG 986; tablets for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AMG 986 Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast)	Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Maximum Observed Plasma Concentration After Dosing (Cmax)	1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Terminal Phase Half-Life (t1/2,z)	Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Time of Maximum Plasma Concentration (Tmax)	Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
AMG 986 PK Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUCinf)	Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event is defined as any untoward medical occurrence in a clinical trial subject. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening (places the subject at immediate risk of death); requires in patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event	From first dose of study drug up to Day 30

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Trivedi A, Mather O, Vega S, Simiens MA, Hellawell J, Lee E. Effect of Severe Renal Impairment on the Safety, Tolerability, and Pharmacokinetics of AMG 986. Drugs R D. 2022 Mar;22(1):89-94. doi: 10.1007/s40268-021-00380-1. Epub 2022 Jan 29.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2017
• Primary Completion (Actual): March 12, 2018
• Study Completion (Actual): April 5, 2018

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: October 20, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): June 23, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Cardiovascular Diseases; Renal Impairment; Heart Diseases
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: 20150186

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No