Clinical trial NCT01372826: Assessing the Pharmacokinetics of NKTR-118 in Subjects With Renal Impairment Compared to That in Subjects With Normal Renal Function
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: Phase 1
Pharmacokinetics
NKTR-118
renal impairment
parallel study
QTcF Interval
AUC(0-t)
Cmax
tmax
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-06-14
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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.

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)
timeFrame: 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.
measure: To assess the pharmacokinetics of a single dose of NKTR-118 25 mg by assessment of maximum concentration (Cmax)
timeFrame: 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 outcomes:
measure: To assess the safety and tolerability of NKTR-118 in subjects with renal impairment and normal renal function by assessing Adverse events.
timeFrame: Duration Day -1 to follow-up at either visit 3 or 6 dependant on treatment
measure: To assess the safety and tolerability of NKTR-118 in subjects with renal impairment and normal renal function by assessing vital signs
timeFrame: Duration Day -1 to follow-up at either visit 3 or 6 dependant on treatment
measure: To assess the safety and tolerability of NKTR-118 in subjects with renal impairment and normal renal function by assessing safety blood samples
timeFrame: Duration Day -1 to follow-up at either visit 3 or 6 dependant on treatment
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Research Site
state: California
city: Orlando
country: United States
facility: Research Site
state: Florida
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 US
name: Thomas Marbury, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.