Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 986 Administered Orally to Healthy Volunteers and Participants With Severely Impaired Renal Function
Condition: Heart Failure
MeSH terms: Renal Insufficiency
Intervention: AMG 986
Intervention description: tablets for oral administration
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: None (Open Label)
Masking description: The patient, investigator, investigative staff, medical monitor and care provider will not be masked for the study.
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Cardiovascular Diseases; Renal Impairment; Heart Diseases

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.
    

Eligibility criteria:

        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).