Clinical trial NCT03318809: Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 986 Administered Orally to Healthy Volunteers and Participants With Severely Impaired Renal Function
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure
Keywords: Cardiovascular Diseases
Renal Impairment
Heart Diseases
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2017-10-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: AMG 986 Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast)
timeFrame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
measure: AMG 986 PK Parameter: Maximum Observed Plasma Concentration After Dosing (Cmax)
timeFrame: 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
measure: AMG 986 PK Parameter: Terminal Phase Half-Life (t1/2,z)
timeFrame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
measure: AMG 986 PK Parameter: Time of Maximum Plasma Concentration (Tmax)
timeFrame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
measure: AMG 986 PK Parameter: Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUCinf)
timeFrame: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to Day 30
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Research Site
state: California
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: San Antonio
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.