Open-label Study to Assess the Pharmacokinetics of NKTR-118 in Patients With Impaired Hepatic Function

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic; Functional Disturbance
• Intervention / Treatment: Drug: NKTR-118

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Normal hepatic function, 25 mg NKTR-118 administered orally	Drug: NKTR-118; 25 mg Oral tablets, single dose
Experimental: Group 2; Mild hepatic impairment, 25 mg NKTR-118 administered orally	Drug: NKTR-118; 25 mg Oral tablets, single dose
Experimental: Group 3; Moderate hepatic impairment, 25 mg NKTR-118 administered orally	Drug: NKTR-118; 25 mg Oral tablets, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)	Duration from predose day 1 to day 6.

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	Duration from day -1 to follow up. ( Approximately 15-18 days)
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	Duration from day -1 to follow up. ( Approximately 15-18 days)
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	Duration from day -1 to follow up. ( Approximately 15-18 days)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Mark Sostek, MD, AstraZeneca; Study Chair: Bo Fransson, MD, AstraZeneca

Publications and helpful links

General Publications

• 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.

Helpful Links

• D3820C00010 Clinical Study Report Synopsis.pdf

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: July 8, 2011
• First Submitted That Met QC Criteria: July 12, 2011
• First Posted (Estimate): July 13, 2011

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 13, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: pharmacokinetics; Phase 1; tmax; AUC; Cmax; NKTR-118; Child-Pugh scale; volunteers with hepatic impairment; t1/2
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxegol
• Other Study ID Numbers: D3820C00010