Clinical trial NCT01392807: Open-label Study to Assess the Pharmacokinetics of NKTR-118 in Patients With Impaired Hepatic Function
Official title: An Open-label, Single-center Study to Assess the Pharmacokinetics of NKTR-118 in Patients With Impaired Hepatic Function and Subjects With Normal Hepatic Function Following Administration of a Single Dose of 25mg NKTR-118
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic; Functional Disturbance
Keywords: Phase 1
volunteers with hepatic impairment
pharmacokinetics
NKTR-118
Child-Pugh scale
AUC
Cmax
tmax
t1/2
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-07-13
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to assess the pharmacokinetics of NKTR-118 in patients with impaired hepatic function versus subjects with normal hepatic function.


Eligibility criteria: Inclusion Criteria:

* Males or females aged 18 years or more with a weight of at least 50 kg and BMI between 18 and 40 kg/m2, inclusive.
* Negative screen for human immunodeficiency virus (HIV)
* For subjects with normal hepatic function, negative results for serum hepatitis B (HBV) surface antigen, HCV antibody, and HIV

Exclusion Criteria:

* Plasma or blood product donation within 1 month of screening or any blood donation/blood loss greater than 500 mL during the 3 months prior to screening.
* History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity
* Known or suspected history of drug/chemical abuse within the past 2 years as judged by the Investigator.
* Subjects with a history of surgery on the gastrointestinal tract.
* For patients with hepatic impairment, fluctuating or rapidly deteriorating hepatic function as indicated by clinical and/or laboratory signs of hepatic impairment (e.g. advanced ascites, infection of ascites, fever, or active gastrointestinal bleeding).

Primary outcomes:
measure: To assess the pharmacokinetics of a single dose of NKTR-118 25 mg by assessment of area under the curve over the time (AUC) and maximum concentration (Cmax)
timeFrame: Duration from predose day 1 to day 6.
Secondary outcomes:
measure: To examine the safety and tolerability of a single oral dose of 25 mg NKTR-118 in patients with impaired hepatic function and in subjects with normal hepatic function by collecting adverse events.
timeFrame: Duration from day -1 to follow up. ( Approximately 15-18 days)
measure: To examine the safety and tolerability of a single oral dose of 25 mg NKTR-118 in patients with impaired hepatic function and in subjects with normal hepatic function by collecting vital signs
timeFrame: Duration from day -1 to follow up. ( Approximately 15-18 days)
measure: To examine the safety and tolerability of a single oral dose of 25 mg NKTR-118 in patients with impaired hepatic function by collecting safety blood samples
timeFrame: Duration from day -1 to follow up. ( Approximately 15-18 days)
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Research Site
state: Kansas
Study officials:
affiliation: AstraZeneca
name: Mark Sostek, MD
role: STUDY_DIRECTOR
affiliation: Orlando Clinical Research Center
name: Thomas Marbury, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Bo Fransson, MD
role: STUDY_CHAIR
References:
citation: Bui K, She F, Sostek M. The effects of mild or moderate hepatic impairment on the pharmacokinetics, safety, and tolerability of naloxegol. J Clin Pharmacol. 2014 Dec;54(12):1368-74. doi: 10.1002/jcph.348. Epub 2014 Jun 27.