Assessing the Pharmacokinetics of NKTR-118 in Subjects With Renal Impairment Compared to That in Subjects With Normal Renal Function

An Open-Label, Parallel-Group, Phase I Study to Compare the Pharmacokinetics of NKTR-118 Following a Single Oral Dose in Subjects With Renal Impairment and Subjects With Normal Renal Function

This study will be assessing the pharmacokinetics of NKTR-118 in subjects with renal impairment compared to that in subjects with normal renal function.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: NKTR118 Group1; Drug: NKTR118 Group 2; Drug: NKTR118 Group3; Drug: NKTR118

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States
      • Research Site
  • Florida
    • Orlando, Florida, United States
      • Research Site
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed written and dated informed consent prior to any study specific procedures.
• Male or female volunteers aged 18 to 80 years (inclusive) having normal renal function, or suffering from moderate or severe renal impairment or ESRD.

Male subjects who are sexually active must be willing to use a barrier method of contraception (condom). Women must be of non-childbearing potential or, if of childbearing potential, must have a negative pregnancy test (at screening and at each admission) and be using a highly effective form of birth control for 3 months before enrollment and be willing to use a highly effective form of birth control during the study and until 3 months after their last dose of IP.

• Have a BMI between 18 and 40 kg/m2 (inclusive) and weigh at least 50 kg.
• Subjects must be able to understand and to comply with study procedures, restrictions and requirements.

Exclusion Criteria:

• History of any clinically significant medical history which, in the opinion of the Investigator and Sponsor, may either put the subject at risk because of participation in the study, or influence the results, or the subject's ability to participate in the study.
• History or presence of gastrointestinal hepatic or other condition known to interfere with disposition of the study drug (except for renal function impairment).
• Subjects who have a functioning kidney transplant.
• Acute illness, surgical procedures or trauma from within 2 weeks before enrollment until first administration of study drug
• Known or suspected history of drug abuse as judged by the Investigator.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NKTR118 Group1; Normal Renal Function	Drug: NKTR118 Group1; Oral dose, 25 mg
Experimental: NKTR118 Group 2; Moderate Renal Function	Drug: NKTR118 Group 2; Oral dose, 25 mg
Experimental: NKTR118 Group 3; Severe Renal Impairment	Drug: NKTR118 Group3; Oral dose, 25 mg
Experimental: NKTR118 Group 4; End-Stage Renal Disease	Drug: NKTR118; Oral dose, 25 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	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)	Groups 1 (normal), 2 (moderate), 3 (severe), and for Group 4 (End-stage renal disease requiring hemodialysis)	PK blood samples will be collected in treatment periods 1 and 2 at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h post-dose.
To assess the pharmacokinetics of a single dose of NKTR-118 25 mg by assessment of maximum concentration (Cmax)	Groups 1 (normal), 2 (moderate), 3 (severe), and for Group 4 (End-stage renal disease requiring hemodialysis)	PK blood samples will be collected in treatment periods 1 and 2 at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 h post-dose.

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the safety and tolerability of NKTR-118 in subjects with renal impairment and normal renal function by assessing Adverse events.	Duration Day -1 to follow-up at either visit 3 or 6 dependant on treatment
To assess the safety and tolerability of NKTR-118 in subjects with renal impairment and normal renal function by assessing vital signs	Duration Day -1 to follow-up at either visit 3 or 6 dependant on treatment
To assess the safety and tolerability of NKTR-118 in subjects with renal impairment and normal renal function by assessing safety blood samples	Duration Day -1 to follow-up at either visit 3 or 6 dependant on treatment

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Mark Sostek, MD, AstraZeneca; Principal Investigator: Thomas Marbury, MD, Orlando Clinical Research Center US

Publications and helpful links

General Publications

• Bui K, She F, Sostek M. The effects of renal impairment on the pharmacokinetics, safety, and tolerability of naloxegol. J Clin Pharmacol. 2014 Dec;54(12):1375-82. doi: 10.1002/jcph.349. Epub 2014 Jul 1.

Helpful Links

• D3820C00009 Clinical Study Report Synopsis

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: May 25, 2011
• First Submitted That Met QC Criteria: June 13, 2011
• First Posted (Estimate): June 14, 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; renal impairment; Cmax; NKTR-118; parallel study; QTcF Interval; AUC(0-t)
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxegol
• Other Study ID Numbers: D3820C00009