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Albiglutide Glucose Clamp Study in Subjects With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01475734
First received: November 17, 2011
Last updated: May 29, 2014
Last verified: May 2014

November 17, 2011
May 29, 2014
December 2011
July 2012   (final data collection date for primary outcome measure)
Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
Plasma glucagon levels were measured for the estimation of glucagon secretion during the hypoglycemic periods. Glucagon response was measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min). Repeated-measures analysis of variance was performed on non-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect. Values below the lower limit of quantification (0.03780 nmol/L) were set to the quantification limit for summary.
Glucagon concentration (nmol/L) [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
Glucagon concentration (nmol/L) during the hypoglycemic periods after treatment with albiglutide or placebo
Complete list of historical versions of study NCT01475734 on ClinicalTrials.gov Archive Site
  • Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    The insulin secretion rate (ISR) was estimated by the deconvolution of peripheral C-peptide concentrations using a 2-compartment model that utilizes population C-peptide kinetic parameters. ISR was measured at 1 hr, 1 hr 15 min, 1 hr 45 min, 2 hr, 2 hr 45 min, 3 hr, 3 hr 30 min, 3 hr 45 min, 4 hr 15 min, and 4 hr 30 min. Repeated-measures analysis of variance was performed on insulin secretion rate using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect.
  • Epinephrine Values During the Glucose Clamp Period [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Epinephrine levels were measured at all stages of glycemia during the glucose clamp period. Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min). Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect. Values below the lower limit of quantification were set to the quantification limit for summary.
  • Norepinephrine Values During the Glucose Clamp Period [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Norepinephrine levels were measured at all stages of glycemia during the glucose clamp period. Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min). Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect. Values below the lower limit of quantification were set to the quantification limit for summary.
  • Growth Hormone Values During the Glucose Clamp Period [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Growth hormone levels were measured at all stages of glycemia during the glucose clamp period. Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min). Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect. Values below the lower limit of quantification were set to the quantification limit for summary.
  • Insulin Values During the Glucose Clamp Period [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Insulin levels were measured at all stages of glycemia during the glucose clamp period. Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min). Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect. Values below the lower limit of quantification were set to the quantification limit for summary.
  • Cortisol Values During the Glucose Clamp Period [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Cortisol levels were measured at all stages of glycemia during the glucose clamp period. Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min). Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect. Values below the lower limit of quantification were set to the quantification limit for summary.
  • C-peptide Values During the Glucose Clamp Period [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    C-peptide levels were measured at all stages of glycemia during the glucose clamp period. Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min). Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect. Values below the lower limit of quantification were set to the quantification limit for summary.
  • Recovery Time of Plasma Glucose Levels to >=3.9 mmol/L (>=70 mg/dL) From the Hypoglycemic Clamp Level of 2.8 Nmol/L (50.4 mg/dL) [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    The effect of albiglutide and placebo on the recovery time of plasma glucose levels to >=3.9 mmol/L (7>=0 mg/dL) from the hypoglycemic clamp level of 2.8 nmol/L (50.4 mg/dL) was calculated as the time in minutes between switching off of the insulin infusion and reaching the level of >=3.9 mmol/L (>=70 mg/dL). Censored values were censored at 70 minutes. The median and 95% confidence interval data are obtained from Kaplan-Meier estimates.
  • Average Albiglutide Concentration on the Day of the Clamp Procedure [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Plasma samples were taken from participants at two time points on Day 4 (at 0 hours and 4 hours and 45 minutes post-dose) of Week 1 of the study for albiglutide study drug level analyses. The average concentration for each participant was calculated as the mean of the concentrations at 0 hours and 4 hours 45 minutes. The clamp procedure is a glucose-controlled insulin infusion system. Variable infusions of glucose are administered to achieve various glucose target levels. It is a way of quantifying insulin secretion and resistance.
  • Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE) and Treatment-emergent Non-serious Adverse Event (AE) During the Clamp Period [ Time Frame: From the time the participant consented to participate in the study through the end of the study, or the final follow-up visit for participants who discontinued active participation in the study (up to 8 study weeks) ] [ Designated as safety issue: No ]
    Treatment-emergent AEs are defined as those with an onset on or after study drug administration. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect.
  • Plasma C-peptide concentration during hypoglycemic periods [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Insulin secretion rate (measured by mathematical analysis of C-peptide concentration) during the hypogycemic periods
  • Glucagon concentration [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Glucagon concentration at all stages of glycemia
  • Plasma C-peptide concentration during all stages of glycemia [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Insulin secretion rate (measured by mathematical analysis of C-peptide concentration) at all stages of glycemia
  • Albiglutide concentration [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Average concentration of albiglutide during the clamp period
  • Number of participants with adverse events [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    Number of participants with adverse events during the clamp period
Not Provided
Not Provided
 
Albiglutide Glucose Clamp Study in Subjects With Type 2 Diabetes
A Single-site, Randomized, Double-blind, Placebo-controlled, Parallel-group, Stepped Glucose Clamp Study to Assess the Effects of Albiglutide on Counter-regulatory Hormone Responses and Recovery From Hypoglycemia in Subjects With Type 2 Diabetes Mellitus.

This is a stepped glucose clamp study designed to investigate the effect of treatment with albiglutide on counter-regulatory hormone responses and recovery from hypoglycemia in subjects with Type 2 diabetes mellitus. A single dose of albiglutide or placebo will be given prior to a stepped hyper- and hypoglycemic clamp. The goal of this study is to demonstrate that albiglutide increases insulin secretion and decreases glucagon levels in a glucose-dependent manner.

This is a Phase II, single-site, randomized, double-blind, parallel-group, placebo-controlled, stepped glucose clamp study designed to investigate the effect of treatment with albiglutide on counter-regulatory hormone responses and recovery from hypoglycemia in subjects with Type 2 diabetes mellitus. A single dose of albiglutide or placebo will be given 3 days before employing a stepped hyper- and hypoglycemic clamp. The goal of this study is to demonstrate that albiglutide increases insulin secretion and decreases glucagon levels in a glucose-dependent manner. In particular, this study is being conducted to ensure that albiglutide does not impair counter-regulatory responses during hypoglycemia.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Diabetes Mellitus, Type 2
  • Biological: albiglutide
    subcutaneous injection
  • Biological: placebo
    subcutaneous injection
  • Active Comparator: albiglutide
    single dose of albiglutide
    Intervention: Biological: albiglutide
  • Placebo Comparator: placebo
    single dose of placebo
    Intervention: Biological: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
44
July 2012
July 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Historical diagnosis of type 2 diabetes mellitus for at least 6 months and less than 10 years before Screening
  • HbA1c <10% at Screening for subjects who do not require washout of existing OAD or <9% at Screening for subjects who do require washout from existing OAD
  • Body mass index in range 28 kg/m2 to40 kg/m2

Exclusion Criteria:

  • History of pancreatitis or current ongoing symptomatic biliary disease or pancreatitis
  • History of significant gastrointestinal surgery,
  • History of significant cardiovascular disease
  • History of a seizure disorder
  • Documented hypertension or hypotension
  • Use of oral antidiabetic agents, except for metformin, within 14 days before investigational product administration.
  • Current hepatic disease or abnormal liver function tests
  • Positive test result for hepatitis B, hepatitis C, or human immunodeficiency virus infection 1 or 2
  • History of regular alcohol consumption (exceeding 7 drinks/week for women or 14 drinks/week for men)
  • Female subject is pregnant (confirmed by laboratory testing), lactating, or less than 6 weeks postpartum
  • Known allergy to any GLP-1 analog or excipients of albiglutide, Baker's yeast, or insulin
  • History of type 1 diabetes,
  • Prior exposure to GLP-1 agents, including albiglutide
  • Blood donation over 500 mL within 8 weeks before Screening
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01475734
108372
Yes
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP