Diabetes Mellitus, Type 2
Conditions
Keywords
glucose clamp, hypoglycemia
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALalbiglutide
subcutaneous injection
BIOLOGICALplacebo
subcutaneous injection
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | Day 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Epinephrine Values During the Glucose Clamp Period | Day 4 | 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 | Day 4 | 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 | Day 4 | 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 | Day 4 | 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. |
| Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | Day 4 | 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. |
| C-peptide Values During the Glucose Clamp Period | Day 4 | 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) | Day 4 | 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 | Day 4 | 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 | 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) | 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. |
| Cortisol Values During the Glucose Clamp Period | Day 4 | 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. |
Countries
United States
Participant flow
Pre-assignment details
Eligible participants entered a 1-week Screening Period, a 2-week Run-in/Stabilization Period, a 4-day Treatment Period for the evaluation of efficacy and safety, and an 8-week post-treatment Follow-up Period. A total of 45 participants were screened, 44 were randomized, and 41 completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Albiglutide 50 mg Participants received a single dose of albiglutide (50 milligrams \[mg\]) subcutaneously 3 days before employing a stepped hyper- and hypoglycemic clamp with glucose plateaus of 9.0, 5.0, 4.0, 3.3, and 2.8 millimoles per liter (mmol/L) (162, 90, 72, 59, and 50.4 milligrams per deciliter \[mg/dL\], respectively). Glucose and insulin infusions were included as part of the clamp procedure. | 22 |
| Placebo Participants received a single dose of matching placebo (50 mg) subcutaneously 3 days before employing a stepped hyper- and hypoglycemic clamp with glucose plateaus of 9.0, 5.0, 4.0, 3.3, and 2.8 mmol/L (162, 90, 72, 59, and 50.4 mg/dL, respectively). Glucose and insulin infusions were included as part of the clamp procedure. | 22 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Albiglutide 50 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 49.9 Years STANDARD_DEVIATION 6.86 | 48.4 Years STANDARD_DEVIATION 9.32 | 49.1 Years STANDARD_DEVIATION 8.12 |
| Gender Female | 12 Participants | 12 Participants | 24 Participants |
| Gender Male | 10 Participants | 10 Participants | 20 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 1 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Mexican | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Persian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 20 Participants | 14 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 22 | 4 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure
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.
Time frame: Day 4
Population: Pharmacodynamic (PD) Population: all participants who received 1 dose of albiglutide or placebo, had a Baseline assessment, and had at least 1 post-Baseline assessment of the primary endpoint (glucagon) during the clamp procedure. PD Population participants were analyzed according to randomly assigned treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 2 hr, n=20, 20 | 0.03805 Nanomoles per liter (nmol/L) | Standard Deviation 1.029775 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 3 hr 45 min, n=20, 21 | 0.04072 Nanomoles per liter (nmol/L) | Standard Deviation 1.146327 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 1 hr, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 4 hr 15 min, n=20, 21 | 0.03976 Nanomoles per liter (nmol/L) | Standard Deviation 1.152056 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 2 hr 45 min, n=20, 21 | 0.03876 Nanomoles per liter (nmol/L) | Standard Deviation 1.090802 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 4 hr 30 min, n=20, 21 | 0.03899 Nanomoles per liter (nmol/L) | Standard Deviation 1.105904 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 1 hr 45 min, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 4 hr 45 min, n=20, 21 | 0.03936 Nanomoles per liter (nmol/L) | Standard Deviation 1.102107 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 3 hr, n=20, 21 | 0.03808 Nanomoles per liter (nmol/L) | Standard Deviation 1.024552 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 5 hr, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 1 hr 15 min, n=20, 21 | 0.03783 Nanomoles per liter (nmol/L) | Standard Deviation 1.003528 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 5 hr 15 min, n=20, 21 | 0.03809 Nanomoles per liter (nmol/L) | Standard Deviation 1.034545 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 3 hr 30 min, n=20, 21 | 0.04296 Nanomoles per liter (nmol/L) | Standard Deviation 1.203416 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 5 hr 30 min, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Albiglutide 50 mg | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 0 hr, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 5 hr 30 min, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 0 hr, n=20, 21 | 0.03805 Nanomoles per liter (nmol/L) | Standard Deviation 1.030606 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 1 hr, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 1 hr 15 min, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 1 hr 45 min, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 2 hr, n=20, 20 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 2 hr 45 min, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 3 hr, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 3 hr 30 min, n=20, 21 | 0.03922 Nanomoles per liter (nmol/L) | Standard Deviation 1.127202 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 3 hr 45 min, n=20, 21 | 0.03893 Nanomoles per liter (nmol/L) | Standard Deviation 1.086818 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 4 hr 15 min, n=20, 21 | 0.04094 Nanomoles per liter (nmol/L) | Standard Deviation 1.19238 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 4 hr 30 min, n=20, 21 | 0.04000 Nanomoles per liter (nmol/L) | Standard Deviation 1.146223 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 4 hr 45 min, n=20, 21 | 0.03958 Nanomoles per liter (nmol/L) | Standard Deviation 1.116342 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 5 hr, n=20, 21 | 0.03814 Nanomoles per liter (nmol/L) | Standard Deviation 1.042285 |
| Placebo | Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure | 5 hr 15 min, n=20, 21 | 0.03780 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
p-value: >0.99995% CI: [0.952, 1.05]ANOVA
p-value: 0.79195% CI: [0.946, 1.043]ANOVA
p-value: >0.99995% CI: [0.952, 1.05]ANOVA
p-value: 0.97595% CI: [0.953, 1.051]ANOVA
p-value: >0.99995% CI: [0.952, 1.05]ANOVA
p-value: 0.90895% CI: [0.955, 1.053]ANOVA
p-value: 0.31295% CI: [0.977, 1.077]ANOVA
p-value: 0.76395% CI: [0.96, 1.058]ANOVA
p-value: <0.00195% CI: [1.043, 1.15]ANOVA
p-value: 0.0795% CI: [0.996, 1.098]ANOVA
p-value: 0.23895% CI: [0.925, 1.02]ANOVA
p-value: 0.29895% CI: [0.928, 1.023]ANOVA
p-value: 0.82195% CI: [0.947, 1.044]ANOVA
p-value: 0.71595% CI: [0.944, 1.04]ANOVA
p-value: 0.75995% CI: [0.96, 1.058]ANOVA
Secondary
Average Albiglutide Concentration on the Day of the Clamp Procedure
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.
Time frame: Day 4
Population: Albiglutide Pharmacokinetic Population: all participants who had at least one sample to compute albiglutide exposure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide 50 mg | Average Albiglutide Concentration on the Day of the Clamp Procedure | Week 1, Day 4, 0 hours | 2110.5 Nanograms per milliliter (ng/mL) | Standard Deviation 905.81 |
| Albiglutide 50 mg | Average Albiglutide Concentration on the Day of the Clamp Procedure | Week 1, Day 4, 4 hours 45 minutes | 1968.7 Nanograms per milliliter (ng/mL) | Standard Deviation 754.37 |
| Albiglutide 50 mg | Average Albiglutide Concentration on the Day of the Clamp Procedure | Average Concentration | 2039.63 Nanograms per milliliter (ng/mL) | Standard Deviation 826.584 |
Secondary
Cortisol Values During the Glucose Clamp Period
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.
Time frame: Day 4
Population: Pharmacodynamic Population. Different participants may have been analyzed at different time points (reflected by n=X, X in the category titles), so the overall number of participants analyzed reflects everyone in the Pharmacodynamic Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 231.0 Nanomoles per liter (nmol/L) | Standard Deviation 2.04 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 667.7 Nanomoles per liter (nmol/L) | Standard Deviation 1.2 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 1 hr, n=20, 21 | 208.9 Nanomoles per liter (nmol/L) | Standard Deviation 2.05 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 746.4 Nanomoles per liter (nmol/L) | Standard Deviation 1.21 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 273.9 Nanomoles per liter (nmol/L) | Standard Deviation 1.88 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 758.2 Nanomoles per liter (nmol/L) | Standard Deviation 1.2 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 233.2 Nanomoles per liter (nmol/L) | Standard Deviation 2.04 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 780.0 Nanomoles per liter (nmol/L) | Standard Deviation 1.18 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 3 hr, n=20, 21 | 392.1 Nanomoles per liter (nmol/L) | Standard Deviation 1.5 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 5 hr, n=20, 21 | 718.9 Nanomoles per liter (nmol/L) | Standard Deviation 1.32 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 1 hr 15 min, n=20, 21 | 207.4 Nanomoles per liter (nmol/L) | Standard Deviation 2.04 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 703.4 Nanomoles per liter (nmol/L) | Standard Deviation 1.2 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 3 hr 30 min, n=20, 21 | 597.0 Nanomoles per liter (nmol/L) | Standard Deviation 1.28 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 646.4 Nanomoles per liter (nmol/L) | Standard Deviation 1.25 |
| Albiglutide 50 mg | Cortisol Values During the Glucose Clamp Period | 0 hr, n=20, 21 | 260.9 Nanomoles per liter (nmol/L) | Standard Deviation 2.05 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 569.0 Nanomoles per liter (nmol/L) | Standard Deviation 1.29 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 0 hr, n=20, 21 | 282.9 Nanomoles per liter (nmol/L) | Standard Deviation 1.46 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 1 hr, n=20, 21 | 250.5 Nanomoles per liter (nmol/L) | Standard Deviation 1.23 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 1 hr 15 min, n=20, 21 | 272.3 Nanomoles per liter (nmol/L) | Standard Deviation 1.27 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 230.2 Nanomoles per liter (nmol/L) | Standard Deviation 1.37 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 230.7 Nanomoles per liter (nmol/L) | Standard Deviation 1.38 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 290.4 Nanomoles per liter (nmol/L) | Standard Deviation 1.59 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 3 hr, n=20, 21 | 344.0 Nanomoles per liter (nmol/L) | Standard Deviation 1.51 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 3 hr 30 min, n=20, 21 | 534.7 Nanomoles per liter (nmol/L) | Standard Deviation 1.36 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 583.0 Nanomoles per liter (nmol/L) | Standard Deviation 1.26 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 674.0 Nanomoles per liter (nmol/L) | Standard Deviation 1.19 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 705.2 Nanomoles per liter (nmol/L) | Standard Deviation 1.18 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 712.0 Nanomoles per liter (nmol/L) | Standard Deviation 1.21 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 5 hr, n=20, 21 | 673.3 Nanomoles per liter (nmol/L) | Standard Deviation 1.24 |
| Placebo | Cortisol Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 626.8 Nanomoles per liter (nmol/L) | Standard Deviation 1.28 |
Secondary
C-peptide Values During the Glucose Clamp Period
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.
Time frame: Day 4
Population: Pharmacodynamic Population. Different participants may have been analyzed at different time points (reflected by n=X, X in the category titles), so the overall number of participants analyzed reflects everyone in the Pharmacodynamic Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 0.723 Nanomoles per liter (nmol/L) | Standard Deviation 2.1648 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 0.140 Nanomoles per liter (nmol/L) | Standard Deviation 1.5595 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 1 hr, n=20, 21 | 1.616 Nanomoles per liter (nmol/L) | Standard Deviation 1.9504 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 0.105 Nanomoles per liter (nmol/L) | Standard Deviation 1.1483 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 0.362 Nanomoles per liter (nmol/L) | Standard Deviation 2.2903 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 0.100 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 0.786 Nanomoles per liter (nmol/L) | Standard Deviation 2.2046 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 0.100 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 3 hr, n=20, 21 | 0.309 Nanomoles per liter (nmol/L) | Standard Deviation 2.2762 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 5 hr, n=20, 21 | 0.105 Nanomoles per liter (nmol/L) | Standard Deviation 1.1483 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 1 hr 15 min, n=20, 21 | 1.630 Nanomoles per liter (nmol/L) | Standard Deviation 1.9941 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 0.118 Nanomoles per liter (nmol/L) | Standard Deviation 1.4512 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 3 hr 30 min, n=20, 21 | 0.152 Nanomoles per liter (nmol/L) | Standard Deviation 1.7438 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 0.141 Nanomoles per liter (nmol/L) | Standard Deviation 1.6701 |
| Albiglutide 50 mg | C-peptide Values During the Glucose Clamp Period | 0 hr, n=20, 21 | 1.095 Nanomoles per liter (nmol/L) | Standard Deviation 1.4141 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 0.138 Nanomoles per liter (nmol/L) | Standard Deviation 1.4534 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 0 hr, n=20, 21 | 0.836 Nanomoles per liter (nmol/L) | Standard Deviation 1.2694 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 1 hr, n=20, 21 | 0.993 Nanomoles per liter (nmol/L) | Standard Deviation 1.853 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 1 hr 15 min, n=20, 21 | 1.053 Nanomoles per liter (nmol/L) | Standard Deviation 1.8949 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 0.517 Nanomoles per liter (nmol/L) | Standard Deviation 1.8094 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 0.484 Nanomoles per liter (nmol/L) | Standard Deviation 1.8073 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 0.275 Nanomoles per liter (nmol/L) | Standard Deviation 1.8736 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 3 hr, n=20, 21 | 0.255 Nanomoles per liter (nmol/L) | Standard Deviation 1.8769 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 3 hr 30 min, n=20, 21 | 0.138 Nanomoles per liter (nmol/L) | Standard Deviation 1.3718 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 0.128 Nanomoles per liter (nmol/L) | Standard Deviation 1.3047 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 0.101 Nanomoles per liter (nmol/L) | Standard Deviation 1.0589 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 0.100 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 0.100 Nanomoles per liter (nmol/L) | Standard Deviation 1 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 5 hr, n=20, 21 | 0.103 Nanomoles per liter (nmol/L) | Standard Deviation 1.0821 |
| Placebo | C-peptide Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 0.120 Nanomoles per liter (nmol/L) | Standard Deviation 1.3662 |
Secondary
Epinephrine Values During the Glucose Clamp Period
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.
Time frame: Day 4
Population: Pharmacodynamic Population. Different participants may have been analyzed at different time points (reflected by n=X, X in the category titles), so the overall number of participants analyzed reflects everyone in the Pharmacodynamic Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 73.2 Nanograms per liter (ng/L) | Standard Deviation 1.44 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 410.3 Nanograms per liter (ng/L) | Standard Deviation 1.93 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 1 hr 15 min, n=18, 19 | 57.8 Nanograms per liter (ng/L) | Standard Deviation 1.37 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 568.3 Nanograms per liter (ng/L) | Standard Deviation 1.93 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 183.9 Nanograms per liter (ng/L) | Standard Deviation 1.89 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 608.7 Nanograms per liter (ng/L) | Standard Deviation 1.8 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 1 hr, n=19, 18 | 60.7 Nanograms per liter (ng/L) | Standard Deviation 1.78 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 477.1 Nanograms per liter (ng/L) | Standard Deviation 1.97 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 3 hr, n=19, 21 | 187.1 Nanograms per liter (ng/L) | Standard Deviation 1.81 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 5 hr, n=20, 21 | 246.6 Nanograms per liter (ng/L) | Standard Deviation 2.04 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 0 hr, n=19, 20 | 56.9 Nanograms per liter (ng/L) | Standard Deviation 1.38 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 172.4 Nanograms per liter (ng/L) | Standard Deviation 2.14 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 3 hr 30 min, n=19, 21 | 429.2 Nanograms per liter (ng/L) | Standard Deviation 1.73 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 132.5 Nanograms per liter (ng/L) | Standard Deviation 1.85 |
| Albiglutide 50 mg | Epinephrine Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 69.1 Nanograms per liter (ng/L) | Standard Deviation 1.38 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 118.2 Nanograms per liter (ng/L) | Standard Deviation 1.62 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 0 hr, n=19, 20 | 59.4 Nanograms per liter (ng/L) | Standard Deviation 1.49 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 1 hr, n=19, 18 | 61.2 Nanograms per liter (ng/L) | Standard Deviation 1.52 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 1 hr 15 min, n=18, 19 | 59.9 Nanograms per liter (ng/L) | Standard Deviation 1.48 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 70.1 Nanograms per liter (ng/L) | Standard Deviation 1.52 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 81.5 Nanograms per liter (ng/L) | Standard Deviation 1.61 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 159.2 Nanograms per liter (ng/L) | Standard Deviation 1.82 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 3 hr, n=19, 21 | 171.1 Nanograms per liter (ng/L) | Standard Deviation 1.97 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 3 hr 30 min, n=19, 21 | 372.3 Nanograms per liter (ng/L) | Standard Deviation 1.97 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 318.8 Nanograms per liter (ng/L) | Standard Deviation 2.21 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 519.5 Nanograms per liter (ng/L) | Standard Deviation 1.92 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 505.6 Nanograms per liter (ng/L) | Standard Deviation 2.18 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 395.4 Nanograms per liter (ng/L) | Standard Deviation 2.15 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 5 hr, n=20, 21 | 225.9 Nanograms per liter (ng/L) | Standard Deviation 2.01 |
| Placebo | Epinephrine Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 154.4 Nanograms per liter (ng/L) | Standard Deviation 1.67 |
Secondary
Growth Hormone Values During the Glucose Clamp Period
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.
Time frame: Day 4
Population: Pharmacodynamic Population. Different participants may have been analyzed at different time points (reflected by n=X, X in the category titles), so the overall number of participants analyzed reflects everyone in the Pharmacodynamic Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 0.60 Micrograms per liter (µg/L) | Standard Deviation 3.343 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 4.36 Micrograms per liter (µg/L) | Standard Deviation 1.868 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 1 hr, n=20, 21 | 0.17 Micrograms per liter (µg/L) | Standard Deviation 2.17 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 3.59 Micrograms per liter (µg/L) | Standard Deviation 1.864 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 2.44 Micrograms per liter (µg/L) | Standard Deviation 2.91 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 3.39 Micrograms per liter (µg/L) | Standard Deviation 1.722 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 0.34 Micrograms per liter (µg/L) | Standard Deviation 3.16 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 3.41 Micrograms per liter (µg/L) | Standard Deviation 1.703 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 3 hr, n=20, 21 | 3.16 Micrograms per liter (µg/L) | Standard Deviation 2.641 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 5 hr, n=20, 21 | 2.55 Micrograms per liter (µg/L) | Standard Deviation 1.778 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 1 hr 15 min, n=20, 21 | 0.16 Micrograms per liter (µg/L) | Standard Deviation 2.294 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 1.77 Micrograms per liter (µg/L) | Standard Deviation 2.03 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 3 hr 30 min, n=20, 21 | 4.83 Micrograms per liter (µg/L) | Standard Deviation 1.764 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 1.07 Micrograms per liter (µg/L) | Standard Deviation 1.906 |
| Albiglutide 50 mg | Growth Hormone Values During the Glucose Clamp Period | 0 hr, n=20, 21 | 0.29 Micrograms per liter (µg/L) | Standard Deviation 3.093 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 1.14 Micrograms per liter (µg/L) | Standard Deviation 2.024 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 0 hr, n=20, 21 | 0.26 Micrograms per liter (µg/L) | Standard Deviation 2.875 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 1 hr, n=20, 21 | 0.23 Micrograms per liter (µg/L) | Standard Deviation 2.791 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 1 hr 15 min, n=20, 21 | 0.26 Micrograms per liter (µg/L) | Standard Deviation 2.722 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 0.41 Micrograms per liter (µg/L) | Standard Deviation 3.729 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 0.59 Micrograms per liter (µg/L) | Standard Deviation 4.696 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 2.25 Micrograms per liter (µg/L) | Standard Deviation 3.08 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 3 hr, n=20, 21 | 3.50 Micrograms per liter (µg/L) | Standard Deviation 1.971 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 3 hr 30 min, n=20, 21 | 4.81 Micrograms per liter (µg/L) | Standard Deviation 1.832 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 4.61 Micrograms per liter (µg/L) | Standard Deviation 1.819 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 4.34 Micrograms per liter (µg/L) | Standard Deviation 1.515 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 4.16 Micrograms per liter (µg/L) | Standard Deviation 1.496 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 3.93 Micrograms per liter (µg/L) | Standard Deviation 1.606 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 5 hr, n=20, 21 | 2.99 Micrograms per liter (µg/L) | Standard Deviation 1.812 |
| Placebo | Growth Hormone Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 1.93 Micrograms per liter (µg/L) | Standard Deviation 1.945 |
Secondary
Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period
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.
Time frame: Day 4
Population: Pharmacodynamic Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide 50 mg | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 1 hr | 0.22992 Milliunits per hour (mU/hr) | Standard Deviation 0.175853 |
| Albiglutide 50 mg | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 1 hr 15 min | 0.32088 Milliunits per hour (mU/hr) | Standard Deviation 0.262743 |
| Albiglutide 50 mg | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 1 hr 45 min | 0.02309 Milliunits per hour (mU/hr) | Standard Deviation 0.15501 |
| Albiglutide 50 mg | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 2 hr | 0.14532 Milliunits per hour (mU/hr) | Standard Deviation 0.152512 |
| Albiglutide 50 mg | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 2 hr 45 min | 0.01411 Milliunits per hour (mU/hr) | Standard Deviation 0.038786 |
| Albiglutide 50 mg | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 3 hr | 0.03145 Milliunits per hour (mU/hr) | Standard Deviation 0.042047 |
| Albiglutide 50 mg | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 3 hr 30 min | -0.02053 Milliunits per hour (mU/hr) | Standard Deviation 0.047566 |
| Albiglutide 50 mg | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 3 hr 45 min | 0.01197 Milliunits per hour (mU/hr) | Standard Deviation 0.015914 |
| Albiglutide 50 mg | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 4 hr 15 min | 0.00892 Milliunits per hour (mU/hr) | Standard Deviation 0.017889 |
| Albiglutide 50 mg | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 4 hr 30 min | 0.01868 Milliunits per hour (mU/hr) | Standard Deviation 0.011193 |
| Placebo | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 3 hr 45 min | 0.01878 Milliunits per hour (mU/hr) | Standard Deviation 0.014128 |
| Placebo | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 1 hr | 0.15487 Milliunits per hour (mU/hr) | Standard Deviation 0.11149 |
| Placebo | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 3 hr | 0.04148 Milliunits per hour (mU/hr) | Standard Deviation 0.038344 |
| Placebo | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 1 hr 15 min | 0.22083 Milliunits per hour (mU/hr) | Standard Deviation 0.143504 |
| Placebo | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 4 hr 30 min | 0.02254 Milliunits per hour (mU/hr) | Standard Deviation 0.003796 |
| Placebo | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 1 hr 45 min | -0.00873 Milliunits per hour (mU/hr) | Standard Deviation 0.052095 |
| Placebo | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 3 hr 30 min | -0.00507 Milliunits per hour (mU/hr) | Standard Deviation 0.033461 |
| Placebo | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 2 hr | 0.08063 Milliunits per hour (mU/hr) | Standard Deviation 0.105769 |
| Placebo | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 4 hr 15 min | 0.01401 Milliunits per hour (mU/hr) | Standard Deviation 0.009209 |
| Placebo | Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period | 2 hr 45 min | 0.02484 Milliunits per hour (mU/hr) | Standard Deviation 0.030589 |
Secondary
Insulin Values During the Glucose Clamp Period
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.
Time frame: Day 4
Population: Pharmacodynamic Population. Different participants may have been analyzed at different time points (reflected by n=X, X in the category titles), so the overall number of participants analyzed reflects everyone in the Pharmacodynamic Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 0 hr, n=20, 21 | 140.5 Picomoles per liter (pmol/L) | Standard Deviation 1.6 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 1000.6 Picomoles per liter (pmol/L) | Standard Deviation 2.66 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 437.4 Picomoles per liter (pmol/L) | Standard Deviation 2.01 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 1738.7 Picomoles per liter (pmol/L) | Standard Deviation 2.09 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 1 hr 15 min, n=20, 21 | 385.9 Picomoles per liter (pmol/L) | Standard Deviation 2.14 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 1057.8 Picomoles per liter (pmol/L) | Standard Deviation 3.6 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 298.3 Picomoles per liter (pmol/L) | Standard Deviation 2.05 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 203.0 Picomoles per liter (pmol/L) | Standard Deviation 2.62 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 1 hr, n=20, 21 | 297.5 Picomoles per liter (pmol/L) | Standard Deviation 2.11 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 5 hr, n=20, 21 | 121.7 Picomoles per liter (pmol/L) | Standard Deviation 2.39 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 250.6 Picomoles per liter (pmol/L) | Standard Deviation 2.03 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 99.5 Picomoles per liter (pmol/L) | Standard Deviation 2.05 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 3 hr 30 min, n=20, 21 | 677.1 Picomoles per liter (pmol/L) | Standard Deviation 2.34 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 94.0 Picomoles per liter (pmol/L) | Standard Deviation 2.02 |
| Albiglutide 50 mg | Insulin Values During the Glucose Clamp Period | 3 hr, n=20, 21 | 680.2 Picomoles per liter (pmol/L) | Standard Deviation 2.1 |
| Placebo | Insulin Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 65.1 Picomoles per liter (pmol/L) | Standard Deviation 2.15 |
| Placebo | Insulin Values During the Glucose Clamp Period | 0 hr, n=20, 21 | 102.4 Picomoles per liter (pmol/L) | Standard Deviation 1.5 |
| Placebo | Insulin Values During the Glucose Clamp Period | 1 hr, n=20, 21 | 183.6 Picomoles per liter (pmol/L) | Standard Deviation 2.07 |
| Placebo | Insulin Values During the Glucose Clamp Period | 1 hr 15 min, n=20, 21 | 270.9 Picomoles per liter (pmol/L) | Standard Deviation 1.84 |
| Placebo | Insulin Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 207.4 Picomoles per liter (pmol/L) | Standard Deviation 2.2 |
| Placebo | Insulin Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 357.3 Picomoles per liter (pmol/L) | Standard Deviation 1.81 |
| Placebo | Insulin Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 191.9 Picomoles per liter (pmol/L) | Standard Deviation 2.52 |
| Placebo | Insulin Values During the Glucose Clamp Period | 3 hr, n=20, 21 | 438.7 Picomoles per liter (pmol/L) | Standard Deviation 2.25 |
| Placebo | Insulin Values During the Glucose Clamp Period | 3 hr 30 min, n=20, 21 | 488.0 Picomoles per liter (pmol/L) | Standard Deviation 2.33 |
| Placebo | Insulin Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 861.2 Picomoles per liter (pmol/L) | Standard Deviation 2.01 |
| Placebo | Insulin Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 887.9 Picomoles per liter (pmol/L) | Standard Deviation 2.91 |
| Placebo | Insulin Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 758.1 Picomoles per liter (pmol/L) | Standard Deviation 2.27 |
| Placebo | Insulin Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 115.5 Picomoles per liter (pmol/L) | Standard Deviation 2.55 |
| Placebo | Insulin Values During the Glucose Clamp Period | 5 hr, n=20, 21 | 75.6 Picomoles per liter (pmol/L) | Standard Deviation 2.37 |
| Placebo | Insulin Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 69.6 Picomoles per liter (pmol/L) | Standard Deviation 2.35 |
Secondary
Norepinephrine Values During the Glucose Clamp Period
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.
Time frame: Day 4
Population: Pharmacodynamic Population. Different participants may have been analyzed at different time points (reflected by n=X, X in the category titles), so the overall number of participants analyzed reflects everyone in the Pharmacodynamic Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 346.3 Nanograms per liter (ng/L) | Standard Deviation 1.42 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 537.5 Nanograms per liter (ng/L) | Standard Deviation 1.57 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 1 hr, n=20, 21 | 347.1 Nanograms per liter (ng/L) | Standard Deviation 1.44 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 624.0 Nanograms per liter (ng/L) | Standard Deviation 1.55 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 425.5 Nanograms per liter (ng/L) | Standard Deviation 1.51 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 649.5 Nanograms per liter (ng/L) | Standard Deviation 1.57 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 347.7 Nanograms per liter (ng/L) | Standard Deviation 1.48 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 605.0 Nanograms per liter (ng/L) | Standard Deviation 1.63 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 3 hr, n=20, 21 | 425.0 Nanograms per liter (ng/L) | Standard Deviation 1.58 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 5 hr , n=20, 21 | 508.4 Nanograms per liter (ng/L) | Standard Deviation 1.61 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 1 hr 15 min, n=19, 21 | 382.3 Nanograms per liter (ng/L) | Standard Deviation 1.4 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 511.3 Nanograms per liter (ng/L) | Standard Deviation 1.56 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 3 hr 30 min, n=20, 21 | 543.2 Nanograms per liter (ng/L) | Standard Deviation 1.59 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 469.4 Nanograms per liter (ng/L) | Standard Deviation 1.5 |
| Albiglutide 50 mg | Norepinephrine Values During the Glucose Clamp Period | 0 hr, n=20, 21 | 340.6 Nanograms per liter (ng/L) | Standard Deviation 1.45 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 5 hr 30 min, n=20, 21 | 444.7 Nanograms per liter (ng/L) | Standard Deviation 1.42 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 0 hr, n=20, 21 | 357.0 Nanograms per liter (ng/L) | Standard Deviation 1.44 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 1 hr, n=20, 21 | 360.9 Nanograms per liter (ng/L) | Standard Deviation 1.55 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 1 hr 15 min, n=19, 21 | 376.2 Nanograms per liter (ng/L) | Standard Deviation 1.57 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 1 hr 45 min, n=20, 21 | 424.6 Nanograms per liter (ng/L) | Standard Deviation 1.48 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 2 hr, n=20, 20 | 382.5 Nanograms per liter (ng/L) | Standard Deviation 1.33 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 2 hr 45 min, n=20, 21 | 421.2 Nanograms per liter (ng/L) | Standard Deviation 1.53 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 3 hr, n=20, 21 | 411.9 Nanograms per liter (ng/L) | Standard Deviation 1.5 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 3 hr 30 min, n=20, 21 | 519.2 Nanograms per liter (ng/L) | Standard Deviation 1.55 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 3 hr 45 min, n=20, 21 | 447.5 Nanograms per liter (ng/L) | Standard Deviation 1.53 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 4 hr 15 min, n=20, 21 | 618.0 Nanograms per liter (ng/L) | Standard Deviation 1.4 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 4 hr 30 min, n=20, 21 | 622.2 Nanograms per liter (ng/L) | Standard Deviation 1.44 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 4 hr 45 min, n=20, 21 | 605.8 Nanograms per liter (ng/L) | Standard Deviation 1.38 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 5 hr , n=20, 21 | 485.4 Nanograms per liter (ng/L) | Standard Deviation 1.3 |
| Placebo | Norepinephrine Values During the Glucose Clamp Period | 5 hr 15 min, n=20, 21 | 464.4 Nanograms per liter (ng/L) | Standard Deviation 1.42 |
Secondary
Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE) and Treatment-emergent Non-serious Adverse Event (AE) During the Clamp Period
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.
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)
Population: Safety Population: all participants who received one dose of albiglutide or placebo. The Safety Population was analyzed according to treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide 50 mg | Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE) and Treatment-emergent Non-serious Adverse Event (AE) During the Clamp Period | Any treatment-emergent non-serious AE | 9 Participants |
| Albiglutide 50 mg | Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE) and Treatment-emergent Non-serious Adverse Event (AE) During the Clamp Period | Any treatment-emergent SAE | 0 Participants |
| Placebo | Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE) and Treatment-emergent Non-serious Adverse Event (AE) During the Clamp Period | Any treatment-emergent non-serious AE | 10 Participants |
| Placebo | Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE) and Treatment-emergent Non-serious Adverse Event (AE) During the Clamp Period | Any treatment-emergent SAE | 0 Participants |
Secondary
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)
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.
Time frame: Day 4
Population: Pharmacodynamic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Albiglutide 50 mg | 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) | 35.00 Minutes |
| Placebo | 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) | 30.00 Minutes |