Trial Outcomes & Findings for Albiglutide Glucose Clamp Study in Subjects With Type 2 Diabetes (NCT NCT01475734)

NCT ID: NCT01475734

Last Updated: 2017-01-11

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 44 participants
• Primary outcome timeframe: Day 4
• Results posted on: 2017-01-11

Participant Flow

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.

Participant milestones

Measure	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.	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.
Overall Study STARTED	22	22
Overall Study COMPLETED	20	21
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	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.	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.
Overall Study Withdrawal by Subject	1	0
Overall Study Protocol Violation	1	0
Overall Study Physician Decision	0	1

Baseline Characteristics

Albiglutide Glucose Clamp Study in Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Measure	Albiglutide 50 mg n=22 Participants 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.	Placebo n=22 Participants 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.	Total n=44 Participants Total of all reporting groups
Age, Continuous	49.9 Years STANDARD_DEVIATION 6.86 • n=93 Participants	48.4 Years STANDARD_DEVIATION 9.32 • n=4 Participants	49.1 Years STANDARD_DEVIATION 8.12 • n=27 Participants
Gender Female	12 Participants n=93 Participants	12 Participants n=4 Participants	24 Participants n=27 Participants
Gender Male	10 Participants n=93 Participants	10 Participants n=4 Participants	20 Participants n=27 Participants
Race/Ethnicity, Customized African American/African Heritage	1 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	20 Participants n=93 Participants	14 Participants n=4 Participants	34 Participants n=27 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Mexican	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Persian	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Albiglutide 50 mg n=20 Participants 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.	Placebo n=21 Participants 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.
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	0.03780 Nanomoles per liter (nmol/L) Standard Deviation 1.000000
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	0.03922 Nanomoles per liter (nmol/L) Standard Deviation 1.127202
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	0.03958 Nanomoles per liter (nmol/L) Standard Deviation 1.116342
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 1.000000	0.03814 Nanomoles per liter (nmol/L) Standard Deviation 1.042285
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 1.000000	0.03805 Nanomoles per liter (nmol/L) Standard Deviation 1.030606
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 1.000000	0.03780 Nanomoles per liter (nmol/L) Standard Deviation 1.000000
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	0.03780 Nanomoles per liter (nmol/L) Standard Deviation 1.000000
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 1.000000	0.03780 Nanomoles per liter (nmol/L) Standard Deviation 1.000000
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	0.03780 Nanomoles per liter (nmol/L) Standard Deviation 1.000000
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	0.03780 Nanomoles per liter (nmol/L) Standard Deviation 1.000000
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	0.03893 Nanomoles per liter (nmol/L) Standard Deviation 1.086818
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	0.04094 Nanomoles per liter (nmol/L) Standard Deviation 1.192380
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	0.04000 Nanomoles per liter (nmol/L) Standard Deviation 1.146223
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	0.03780 Nanomoles per liter (nmol/L) Standard Deviation 1.000000
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 1.000000	0.03780 Nanomoles per liter (nmol/L) Standard Deviation 1.000000

SECONDARY outcome

Timeframe: Day 4

Population: Pharmacodynamic Population

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.

Outcome measures

Measure	Albiglutide 50 mg n=20 Participants 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.	Placebo n=21 Participants 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.
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	0.22083 Milliunits per hour (mU/hr) Standard Deviation 0.143504
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 0.155010	-0.00873 Milliunits per hour (mU/hr) Standard Deviation 0.052095
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	0.08063 Milliunits per hour (mU/hr) Standard Deviation 0.105769
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	0.02484 Milliunits per hour (mU/hr) Standard Deviation 0.030589
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	0.04148 Milliunits per hour (mU/hr) Standard Deviation 0.038344
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	-0.00507 Milliunits per hour (mU/hr) Standard Deviation 0.033461
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	0.01878 Milliunits per hour (mU/hr) Standard Deviation 0.014128
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	0.02254 Milliunits per hour (mU/hr) Standard Deviation 0.003796
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	0.01401 Milliunits per hour (mU/hr) Standard Deviation 0.009209
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	0.15487 Milliunits per hour (mU/hr) Standard Deviation 0.111490

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Albiglutide 50 mg n=20 Participants 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.	Placebo n=21 Participants 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.
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	372.3 Nanograms per liter (ng/L) Standard Deviation 1.97
Epinephrine Values During the Glucose Clamp Period 0 hr, n=19, 20	56.9 Nanograms per liter (ng/L) Standard Deviation 1.38	59.4 Nanograms per liter (ng/L) Standard Deviation 1.49
Epinephrine Values During the Glucose Clamp Period 1 hr, n=19, 18	60.7 Nanograms per liter (ng/L) Standard Deviation 1.78	61.2 Nanograms per liter (ng/L) Standard Deviation 1.52
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	59.9 Nanograms per liter (ng/L) Standard Deviation 1.48
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	70.1 Nanograms per liter (ng/L) Standard Deviation 1.52
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	159.2 Nanograms per liter (ng/L) Standard Deviation 1.82
Epinephrine Values During the Glucose Clamp Period 3 hr, n=19, 21	187.1 Nanograms per liter (ng/L) Standard Deviation 1.81	171.1 Nanograms per liter (ng/L) Standard Deviation 1.97
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	318.8 Nanograms per liter (ng/L) Standard Deviation 2.21
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	519.5 Nanograms per liter (ng/L) Standard Deviation 1.92
Epinephrine Values During the Glucose Clamp Period 4 hr 30 min, n=20, 21	608.7 Nanograms per liter (ng/L) Standard Deviation 1.80	505.6 Nanograms per liter (ng/L) Standard Deviation 2.18
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	395.4 Nanograms per liter (ng/L) Standard Deviation 2.15
Epinephrine Values During the Glucose Clamp Period 5 hr, n=20, 21	246.6 Nanograms per liter (ng/L) Standard Deviation 2.04	225.9 Nanograms per liter (ng/L) Standard Deviation 2.01
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	154.4 Nanograms per liter (ng/L) Standard Deviation 1.67
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	118.2 Nanograms per liter (ng/L) Standard Deviation 1.62
Epinephrine Values During the Glucose Clamp Period 2 hr, n=20, 20	73.2 Nanograms per liter (ng/L) Standard Deviation 1.44	81.5 Nanograms per liter (ng/L) Standard Deviation 1.61

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Albiglutide 50 mg n=20 Participants 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.	Placebo n=21 Participants 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.
Norepinephrine Values During the Glucose Clamp Period 0 hr, n=20, 21	340.6 Nanograms per liter (ng/L) Standard Deviation 1.45	357.0 Nanograms per liter (ng/L) Standard Deviation 1.44
Norepinephrine Values During the Glucose Clamp Period 1 hr, n=20, 21	347.1 Nanograms per liter (ng/L) Standard Deviation 1.44	360.9 Nanograms per liter (ng/L) Standard Deviation 1.55
Norepinephrine Values During the Glucose Clamp Period 1 hr 15 min, n=19, 21	382.3 Nanograms per liter (ng/L) Standard Deviation 1.40	376.2 Nanograms per liter (ng/L) Standard Deviation 1.57
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	424.6 Nanograms per liter (ng/L) Standard Deviation 1.48
Norepinephrine Values During the Glucose Clamp Period 2 hr, n=20, 20	346.3 Nanograms per liter (ng/L) Standard Deviation 1.42	382.5 Nanograms per liter (ng/L) Standard Deviation 1.33
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	421.2 Nanograms per liter (ng/L) Standard Deviation 1.53
Norepinephrine Values During the Glucose Clamp Period 3 hr, n=20, 21	425.0 Nanograms per liter (ng/L) Standard Deviation 1.58	411.9 Nanograms per liter (ng/L) Standard Deviation 1.50
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	519.2 Nanograms per liter (ng/L) Standard Deviation 1.55
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	447.5 Nanograms per liter (ng/L) Standard Deviation 1.53
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	618.0 Nanograms per liter (ng/L) Standard Deviation 1.40
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	622.2 Nanograms per liter (ng/L) Standard Deviation 1.44
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	605.8 Nanograms per liter (ng/L) Standard Deviation 1.38
Norepinephrine Values During the Glucose Clamp Period 5 hr , n=20, 21	508.4 Nanograms per liter (ng/L) Standard Deviation 1.61	485.4 Nanograms per liter (ng/L) Standard Deviation 1.30
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	464.4 Nanograms per liter (ng/L) Standard Deviation 1.42
Norepinephrine Values During the Glucose Clamp Period 5 hr 30 min, n=20, 21	469.4 Nanograms per liter (ng/L) Standard Deviation 1.50	444.7 Nanograms per liter (ng/L) Standard Deviation 1.42

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Albiglutide 50 mg n=20 Participants 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.	Placebo n=21 Participants 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.
Growth Hormone Values During the Glucose Clamp Period 0 hr, n=20, 21	0.29 Micrograms per liter (µg/L) Standard Deviation 3.093	0.26 Micrograms per liter (µg/L) Standard Deviation 2.875
Growth Hormone Values During the Glucose Clamp Period 1 hr, n=20, 21	0.17 Micrograms per liter (µg/L) Standard Deviation 2.170	0.23 Micrograms per liter (µg/L) Standard Deviation 2.791
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	0.26 Micrograms per liter (µg/L) Standard Deviation 2.722
Growth Hormone Values During the Glucose Clamp Period 1 hr 45 min, n=20, 21	0.34 Micrograms per liter (µg/L) Standard Deviation 3.160	0.41 Micrograms per liter (µg/L) Standard Deviation 3.729
Growth Hormone Values During the Glucose Clamp Period 2 hr, n=20, 20	0.60 Micrograms per liter (µg/L) Standard Deviation 3.343	0.59 Micrograms per liter (µg/L) Standard Deviation 4.696
Growth Hormone Values During the Glucose Clamp Period 2 hr 45 min, n=20, 21	2.44 Micrograms per liter (µg/L) Standard Deviation 2.910	2.25 Micrograms per liter (µg/L) Standard Deviation 3.080
Growth Hormone Values During the Glucose Clamp Period 3 hr, n=20, 21	3.16 Micrograms per liter (µg/L) Standard Deviation 2.641	3.50 Micrograms per liter (µg/L) Standard Deviation 1.971
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	4.81 Micrograms per liter (µg/L) Standard Deviation 1.832
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	4.61 Micrograms per liter (µg/L) Standard Deviation 1.819
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	4.34 Micrograms per liter (µg/L) Standard Deviation 1.515
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	4.16 Micrograms per liter (µg/L) Standard Deviation 1.496
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	3.93 Micrograms per liter (µg/L) Standard Deviation 1.606
Growth Hormone Values During the Glucose Clamp Period 5 hr, n=20, 21	2.55 Micrograms per liter (µg/L) Standard Deviation 1.778	2.99 Micrograms per liter (µg/L) Standard Deviation 1.812
Growth Hormone Values During the Glucose Clamp Period 5 hr 15 min, n=20, 21	1.77 Micrograms per liter (µg/L) Standard Deviation 2.030	1.93 Micrograms per liter (µg/L) Standard Deviation 1.945
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	1.14 Micrograms per liter (µg/L) Standard Deviation 2.024

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Albiglutide 50 mg n=20 Participants 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.	Placebo n=21 Participants 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.
Insulin Values During the Glucose Clamp Period 0 hr, n=20, 21	140.5 Picomoles per liter (pmol/L) Standard Deviation 1.60	102.4 Picomoles per liter (pmol/L) Standard Deviation 1.50
Insulin Values During the Glucose Clamp Period 1 hr, n=20, 21	297.5 Picomoles per liter (pmol/L) Standard Deviation 2.11	183.6 Picomoles per liter (pmol/L) Standard Deviation 2.07
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	270.9 Picomoles per liter (pmol/L) Standard Deviation 1.84
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	207.4 Picomoles per liter (pmol/L) Standard Deviation 2.20
Insulin Values During the Glucose Clamp Period 2 hr, n=20, 20	437.4 Picomoles per liter (pmol/L) Standard Deviation 2.01	357.3 Picomoles per liter (pmol/L) Standard Deviation 1.81
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	191.9 Picomoles per liter (pmol/L) Standard Deviation 2.52
Insulin Values During the Glucose Clamp Period 3 hr, n=20, 21	680.2 Picomoles per liter (pmol/L) Standard Deviation 2.10	438.7 Picomoles per liter (pmol/L) Standard Deviation 2.25
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	488.0 Picomoles per liter (pmol/L) Standard Deviation 2.33
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	861.2 Picomoles per liter (pmol/L) Standard Deviation 2.01
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	887.9 Picomoles per liter (pmol/L) Standard Deviation 2.91
Insulin Values During the Glucose Clamp Period 4 hr 30 min, n=20, 21	1057.8 Picomoles per liter (pmol/L) Standard Deviation 3.60	758.1 Picomoles per liter (pmol/L) Standard Deviation 2.27
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	115.5 Picomoles per liter (pmol/L) Standard Deviation 2.55
Insulin Values During the Glucose Clamp Period 5 hr, n=20, 21	121.7 Picomoles per liter (pmol/L) Standard Deviation 2.39	75.6 Picomoles per liter (pmol/L) Standard Deviation 2.37
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	69.6 Picomoles per liter (pmol/L) Standard Deviation 2.35
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	65.1 Picomoles per liter (pmol/L) Standard Deviation 2.15

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Albiglutide 50 mg n=20 Participants 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.	Placebo n=21 Participants 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.
Cortisol Values During the Glucose Clamp Period 0 hr, n=20, 21	260.9 Nanomoles per liter (nmol/L) Standard Deviation 2.05	282.9 Nanomoles per liter (nmol/L) Standard Deviation 1.46
Cortisol Values During the Glucose Clamp Period 1 hr, n=20, 21	208.9 Nanomoles per liter (nmol/L) Standard Deviation 2.05	250.5 Nanomoles per liter (nmol/L) Standard Deviation 1.23
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	272.3 Nanomoles per liter (nmol/L) Standard Deviation 1.27
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	230.2 Nanomoles per liter (nmol/L) Standard Deviation 1.37
Cortisol Values During the Glucose Clamp Period 2 hr, n=20, 20	231.0 Nanomoles per liter (nmol/L) Standard Deviation 2.04	230.7 Nanomoles per liter (nmol/L) Standard Deviation 1.38
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	290.4 Nanomoles per liter (nmol/L) Standard Deviation 1.59
Cortisol Values During the Glucose Clamp Period 3 hr, n=20, 21	392.1 Nanomoles per liter (nmol/L) Standard Deviation 1.50	344.0 Nanomoles per liter (nmol/L) Standard Deviation 1.51
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	534.7 Nanomoles per liter (nmol/L) Standard Deviation 1.36
Cortisol Values During the Glucose Clamp Period 3 hr 45 min, n=20, 21	667.7 Nanomoles per liter (nmol/L) Standard Deviation 1.20	583.0 Nanomoles per liter (nmol/L) Standard Deviation 1.26
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	674.0 Nanomoles per liter (nmol/L) Standard Deviation 1.19
Cortisol Values During the Glucose Clamp Period 4 hr 30 min, n=20, 21	758.2 Nanomoles per liter (nmol/L) Standard Deviation 1.20	705.2 Nanomoles per liter (nmol/L) Standard Deviation 1.18
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	712.0 Nanomoles per liter (nmol/L) Standard Deviation 1.21
Cortisol Values During the Glucose Clamp Period 5 hr, n=20, 21	718.9 Nanomoles per liter (nmol/L) Standard Deviation 1.32	673.3 Nanomoles per liter (nmol/L) Standard Deviation 1.24
Cortisol Values During the Glucose Clamp Period 5 hr 15 min, n=20, 21	703.4 Nanomoles per liter (nmol/L) Standard Deviation 1.20	626.8 Nanomoles per liter (nmol/L) Standard Deviation 1.28
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	569.0 Nanomoles per liter (nmol/L) Standard Deviation 1.29

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Albiglutide 50 mg n=20 Participants 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.	Placebo n=21 Participants 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.
C-peptide Values During the Glucose Clamp Period 0 hr, n=20, 21	1.095 Nanomoles per liter (nmol/L) Standard Deviation 1.4141	0.836 Nanomoles per liter (nmol/L) Standard Deviation 1.2694
C-peptide Values During the Glucose Clamp Period 1 hr, n=20, 21	1.616 Nanomoles per liter (nmol/L) Standard Deviation 1.9504	0.993 Nanomoles per liter (nmol/L) Standard Deviation 1.8530
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	1.053 Nanomoles per liter (nmol/L) Standard Deviation 1.8949
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	0.517 Nanomoles per liter (nmol/L) Standard Deviation 1.8094
C-peptide Values During the Glucose Clamp Period 2 hr, n=20, 20	0.723 Nanomoles per liter (nmol/L) Standard Deviation 2.1648	0.484 Nanomoles per liter (nmol/L) Standard Deviation 1.8073
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	0.275 Nanomoles per liter (nmol/L) Standard Deviation 1.8736
C-peptide Values During the Glucose Clamp Period 3 hr, n=20, 21	0.309 Nanomoles per liter (nmol/L) Standard Deviation 2.2762	0.255 Nanomoles per liter (nmol/L) Standard Deviation 1.8769
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	0.138 Nanomoles per liter (nmol/L) Standard Deviation 1.3718
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	0.128 Nanomoles per liter (nmol/L) Standard Deviation 1.3047
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	0.101 Nanomoles per liter (nmol/L) Standard Deviation 1.0589
C-peptide Values During the Glucose Clamp Period 4 hr 30 min, n=20, 21	0.100 Nanomoles per liter (nmol/L) Standard Deviation 1.0000	0.100 Nanomoles per liter (nmol/L) Standard Deviation 1.0000
C-peptide Values During the Glucose Clamp Period 4 hr 45 min, n=20, 21	0.100 Nanomoles per liter (nmol/L) Standard Deviation 1.0000	0.100 Nanomoles per liter (nmol/L) Standard Deviation 1.0000
C-peptide Values During the Glucose Clamp Period 5 hr, n=20, 21	0.105 Nanomoles per liter (nmol/L) Standard Deviation 1.1483	0.103 Nanomoles per liter (nmol/L) Standard Deviation 1.0821
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	0.120 Nanomoles per liter (nmol/L) Standard Deviation 1.3662
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	0.138 Nanomoles per liter (nmol/L) Standard Deviation 1.4534

SECONDARY outcome

Timeframe: Day 4

Population: Pharmacodynamic Population

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.

Outcome measures

Measure	Albiglutide 50 mg n=20 Participants 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.	Placebo n=21 Participants 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.
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 Interval 30.0 to 45.0	30.00 Minutes Interval 25.0 to 40.0

SECONDARY outcome

Timeframe: Day 4

Population: Albiglutide Pharmacokinetic Population: all participants who had at least one sample to compute albiglutide exposure

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.

Outcome measures

Measure	Albiglutide 50 mg n=19 Participants 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.	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.
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	—
Average Albiglutide Concentration on the Day of the Clamp Procedure Average Concentration	2039.63 Nanograms per milliliter (ng/mL) Standard Deviation 826.584	—
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	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Albiglutide 50 mg n=22 Participants 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.	Placebo n=22 Participants 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.
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	10 Participants
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	0 Participants

Adverse Events

Albiglutide 50 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Albiglutide 50 mg n=22 participants at risk 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.	Placebo n=22 participants at risk 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.
Nervous system disorders Headache	4.5% 1/22 • SAEs and non-serious AEs were collected 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 weeks). On-therapy SAEs and non-serious AEs (onset on or after the first day of study medication) were collected in members of the Safety Population, comprised of all randomly assigned study participants who received at least one dose of study medication.	9.1% 2/22 • SAEs and non-serious AEs were collected 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 weeks). On-therapy SAEs and non-serious AEs (onset on or after the first day of study medication) were collected in members of the Safety Population, comprised of all randomly assigned study participants who received at least one dose of study medication.
Infections and infestations Gastroenteritis	0.00% 0/22 • SAEs and non-serious AEs were collected 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 weeks). On-therapy SAEs and non-serious AEs (onset on or after the first day of study medication) were collected in members of the Safety Population, comprised of all randomly assigned study participants who received at least one dose of study medication.	9.1% 2/22 • SAEs and non-serious AEs were collected 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 weeks). On-therapy SAEs and non-serious AEs (onset on or after the first day of study medication) were collected in members of the Safety Population, comprised of all randomly assigned study participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	9.1% 2/22 • SAEs and non-serious AEs were collected 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 weeks). On-therapy SAEs and non-serious AEs (onset on or after the first day of study medication) were collected in members of the Safety Population, comprised of all randomly assigned study participants who received at least one dose of study medication.	0.00% 0/22 • SAEs and non-serious AEs were collected 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 weeks). On-therapy SAEs and non-serious AEs (onset on or after the first day of study medication) were collected in members of the Safety Population, comprised of all randomly assigned study participants who received at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER