Clinical trial NCT00938158: A Study of the Pharmacokinetics of Albiglutide in Normal and Renally Impaired Subjects.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: albiglutide
hemodialysis
pharmacokinetics
renal
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-07-13
Enrollment: 75
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 42 days
Secondary outcomes:
measure: To assess the PK of albiglutide in subjects with varying degrees of proteinuria
timeFrame: 42 days
measure: To assess the effects of hemodialysis on the overall PK profile of albiglutide
timeFrame: 42 days
measure: 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
timeFrame: 42 days
Other outcomes:
Locations:
city: Anniston
country: United States
facility: GSK Investigational Site
state: Alabama
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Baton Rouge
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Parktown
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Somerset West
country: South Africa
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Young MA, Wald JA, Matthews JE, Scott R, Hodge RJ, Zhi H, Reinhardt RR. Clinical pharmacology of albiglutide, a GLP-1 receptor agonist. Postgrad Med. 2014 Nov;126(7):84-97. doi: 10.3810/pgm.2014.11.2836.
citation: Young MA, Wald JA, Matthews JE, Yang F, Reinhardt RR. Effect of renal impairment on the pharmacokinetics, efficacy, and safety of albiglutide. Postgrad Med. 2014 May;126(3):35-46. doi: 10.3810/pgm.2014.05.2754.