A Study of the Pharmacokinetics of Albiglutide in Normal and Renally Impaired Subjects.

Study Overview
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Brief Summary
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The purpose of this study is to assess the pharmacokinetics and safety of a single subcutaneously injected dose of albiglutide in subjects with type 2 diabetes mellitus with varying degrees of renal function, including subjects requiring hemodialysis.

Detailed Description
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This adaptive design, non-randomized, open-label, staggered parallel group study evaluates the pharmacokinetics and safety of a single subcutaneously injected dose of albiglutide in subjects with type 2 diabetes mellitus with varying degrees of renal function. During Stage 1, a single dose of albiglutide will be administered to subjects with normal renal function and subjects with moderate-to-severe renal impairment not requiring hemodialysis. In addition to subjects with normal renal function and moderate renal impairment, Stage 2 of the study will also include cohorts of subjects requiring hemodialysis, subjects with severe renal impairment not requiring hemodialysis, and potentially subjects with mild renal impairment.

Official Title
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An Adaptive Design Study for the Assessment of the Pharmacokinetics of Albiglutide in Subjects With Normal Renal Function and Subjects With Moderate-to-severe Renal Impairment and Hemodialysis.

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Biological: albiglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: normal renal function or renal impairment stable hemodialysis treatment for at least 3 months before screening and able to tolerate a hemodialysis treatment lasting 3-4 hours with blood flow rates of >200mL/min (cohort 3 only) neither pregnant nor lactating HbA1c 6-10.5% inclusive females of childbearing potential must be practicing adequate contraception. Exclusion Criteria: inability to meet the PK objectives of the study history of hypoglycemia unawareness or severe hypoglycemia liver function tests greater than or equal to 2 times the ULN clinically significant cardiovascular and/or cerebrovascular disease positive test results for hepatitis B, hepatitis C, or HIV documented hypertension or hypotension at screening known hepatic or biliary abnormalities current use of sulfonylureas active history of tobacco use within 6 months before screening donation of blood in excess of 500mL within 56 days before albiglutide dosing receipt of any investigational drug within the 30days or 5 half lives, whichever is longer, before dosing previous or current receipt of exenatide or any other GLP-1 agonist

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage 1 normal renal function<br>Subject with estimated glomerular filtration rate (GFR) greater than 80 milliliter per minute (mL/min) | Biological: albiglutide<br>* single dose of subcutaneously injected albiglutide<br>|
| Experimental: Stage 1 moderate/severe renal function<br>Subject with estimated GFR >= 20 mL/min and less than 50 mL/min | Biological: albiglutide<br>* single dose of subcutaneously injected albiglutide<br>|
| Experimental: Stage 2 normal renal function<br>Subject with GFR greater than 80 mL/min | Biological: albiglutide<br>* single dose of subcutaneously injected albiglutide<br>|
| Experimental: Stage 2 moderate renal impairment<br>Subject with estimated GFR >= 30 mL/min and less than 50 mL/min | Biological: albiglutide<br>* single dose of subcutaneously injected albiglutide<br>|
| Experimental: Stage 2 subjects requiring hemodialysis<br>Subjects who require hemodialysis | Biological: albiglutide<br>* single dose of subcutaneously injected albiglutide<br>|
| Experimental: Stage 2 severe renal impairment not requiring hemodialysis<br>Subjects with GFR less than 30 mL/min | Biological: albiglutide<br>* single dose of subcutaneously injected albiglutide<br>|
| Experimental: Stage 2 mild renal impairment<br>Subjects with GFR >= 50 mL/min and <= 80 mL/min | Biological: albiglutide<br>* single dose of subcutaneously injected albiglutide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective is to characterize the PK of albiglutide in subjects with type 2 diabetes and varying degrees of renal impairment, including subjects requiring hemodialysis, and in age, gender and BMI-matched subjects. |  | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the PK of albiglutide in subjects with varying degrees of proteinuria |  | 42 days | 
| To assess the effects of hemodialysis on the overall PK profile of albiglutide |  | 42 days | 
| To assess the safety and tolerability of a single dose of albiglutide in subjects with varying degrees of renal impairment and in age, gender and BMI-matched subjects with normal renal function |  | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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albiglutide, hemodialysis, pharmacokinetics, renal