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

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

Official Title
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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

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: NKTR118 Group1
* Drug: NKTR118 Group 2
* Drug: NKTR118 Group3
* Drug: NKTR118


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Pharmacokinetics, NKTR-118, renal impairment, parallel study, QTcF Interval, AUC(0-t), Cmax, tmax