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

NCT03318809 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 20150186
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Heart Failure

Keywords

Cardiovascular Diseases; Renal Impairment; Heart Diseases

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  From first dose of study drug up to Day 30

Study Arms (2)

Group 1: Severely Renal Impaired Participants

EXPERIMENTAL

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

Group 2: Healthy Participants

ACTIVE COMPARATOR

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

Interventions

AMG 986 DRUG

tablets for oral administration

Group 1: Severely Renal Impaired Participants; Group 2: Healthy Participants

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Amgen: lead

Study Sites (4)

Research Site

Tustin, California, 92780, United States

Location

Research Site

Orlando, Florida, 32809, United States

Location

Research Site

Minneapolis, Minnesota, 55404, United States

Location

Research Site

San Antonio, Texas, 78215, United States

Location

Related Publications (1)

• 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.

  PMID: 35092583 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Heart Failure; Cardiovascular Diseases; Renal Insufficiency; Heart Diseases

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: The patient, investigator, investigative staff, medical monitor and care provider will not be masked for the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multisite (approximately 3 sites), open-label, non-randomized, single-dose study in participants with severely impaired kidney function and healthy participants. About 12 participants will be assigned to two groups: Group 1: 6 with severely impaired kidney function , and Group 2: 6 with normal kidney function.

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: October 24, 2017
• Study Start: December 12, 2017
• Primary Completion: March 12, 2018
• Study Completion: April 5, 2018
• Last Updated: June 23, 2022
• Results First Posted: January 27, 2021

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

US (4)