Clinical trial NCT01737866: Pharmacokinetics Study of AMG 423 in Healthy Subjects and Subjects With Various Degrees of Renal Insufficiency
Official title: An Open-label, Single-dose Study of the Safety, Tolerability, and Pharmacokinetics of AMG 423 in Healthy Subjects and Subjects With Various Degrees of Renal Insufficiency and Effect of Hemodialysis on AMG 423 Pharmacokinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure
Keywords: Heart, Failure, Renal, Insufficiency, Cardiac, Kidney, Hemodialysis, Impairment, omecamtiv mecarbil, cardiac myosin activator, CK-1827452
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2012-11-30
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A phase 1, open-label study in subjects with normal renal function and subjects with various degrees of renal insufficiency, including patients with end-stage renal disease (ESRD) requiring hemodialysis. The primary objective is to evaluate the single-dose PK of AMG 423 in subjects with various degrees of renal insufficiency, including patients with end-stage renal disease requiring hemodialysis.

Detailed description: This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.

Eligibility criteria: Inclusion Criteria:

* Men or women ≥18 years of age
* Laboratory test values (clinical chemistry and hematology)within normal limits, (other than test values out of the normal range for subjects with CKD \[groups 1 and 3 through 5\]), or clinically acceptable to the investigator and sponsor at screening and day -3
* Free of any clinically significant disease or condition(s) (other than that consistent with CKD for subjects in groups 1 and 3 through 5) that require a physician's care and/or would interfere with the evaluations, procedures, or participation in the study per the investigator's discretion;

Exclusion Criteria:

* Subjects whose second MDRD eGFR result during the screening period is not within 10% of the first eGFR result
* Subjects who have received a functioning renal transplant within the past year
* Subjects with ESRD who do not have a functioning hemodialysis access
* Subjects with hemodynamic instability during hemodialysis
* Subjects whose renal insufficiency is due to active autoimmune renal disease
* Subjects with renal insufficiency or ESRD requiring hemodialysis and Troponin I \> upper limit of normal (ULN) at screening or day -3
* Subjects with history of heart disease or unstable angina within the last 3 months
* Subjects with uncontrolled diabetes (Hb1Ac \> 8%) and/or subjects who are able but unwilling to adhere to the required fasting intervals

Primary outcomes:
measure: AMG 423 Pharmacokinetic Parameters
timeFrame: Twenty time points, up to eight days
Secondary outcomes:
measure: Other Total AMG 423 PK Parameters
timeFrame: Twenty time points, up to eight days
measure: AMG 423 Dialysis Clearance
timeFrame: Hours 4, 5, 6, 7 & 8 post-dose
measure: AMG 423 Metabolites
timeFrame: Twenty time points, up to eight days
measure: Safety
timeFrame: Up to 46 days, including a 28 day screening period
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Research Site
state: Florida
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: