Diabetes Mellitus, Type 2
Conditions
Keywords
albiglutide, Japanese, GSK716155, Type 2 diabetes mellitus, glucagon-like peptide 1
Brief summary
This study is designed to examine the efficacy and safety of 2 dose levels of weekly subcutaneously injected albiglutide compared with placebo and an open label reference arm of daily subcutaneous injections of liraglutide, in Japanese subjects with Type 2 diabetes mellitus.
Interventions
DRUGAlbiglutide 30 mg weekly
Albiglutide will be available as a pen injector that delivers 30mg of albiglutide
DRUGAlbiglutide 50 mg weekly
Albiglutide will be available as a pen injector that delivers 50mg of albiglutide
DRUGPlacebo
Albiglutide matching placebo will be available as a pen injector
DRUGLiraglutide 0.9 mg daily
Liraglutide will be available as prefilled multidose pens that can deliver 0.9 mg dose
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with diagnosis of Type 2 Diabetes Mellitus, treated with diet and exercise or a stable dose of 1 OAD at screening * Body mass index (BMI) 17 to 40 kg/ m\^2 inclusive * Subjects who are OAD naïve, HbA1c between 7.0% and 10.0% at Screening and at Visit 2; for subjects who enter the study with 1 OAD, HbA1c between 6.5% and 9.5% at Screening and HbA1c between 7.0% and 10.0% at Visit 2 * Creatinine clearance \>30 mL/min (calculated using the Cockcroft-Gault formula)
Exclusion criteria
* History of type 1 diabetes mellitus •Female subject is pregnant, lactating, or \<6 weeks postpartum• * Clinically significant cardiovascular and/or cerebrovascular disease * Current ongoing symptomatic biliary disease, clinical signs or symptoms of pancreatitis, or a history of chronic or acute pancreatitis, as determined by the investigator * Serum amylase \>=3 ×ULN and/or serum lipase \>=2 × ULN and/or subject is experiencing any symptoms possibly related to pancreatitis * Prior use of a TZD or GLP-1R agonist within 4 months before Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Model-adjusted Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | Baseline and Week 24 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. The Baseline HbA1c value is defined as the last nonmissing value before the start of treatment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. Based on analysis of covariance (ANCOVA): Change at Week 24 = treatment (placebo, albiglutide 30 mg, albiglutide 50 mg) + Baseline HbA1c + prior diabetes therapy + age category (\<65 years versus ≥65 years). Participants who discontinued from study treatment before Week 24 had their last post-Baseline HbA1c carried forward for the analysis unless the value is past 14 days after the last dose of study drug. The open-label liraglutide group was a reference group and not included in the primary endpoint analysis model. Descriptive summary statistics are provided as a separate outcome measure. |
| Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Baseline and Week 24 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. The Baseline HbA1c value is defined as the last nonmissing value before the start of treatment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. Participants who discontinued from study treatment before Week 24 had their last post-Baseline HbA1c value carried forward for the summary, unless the value was past 14 days after the last dose of study drug. The open-label liraglutide group was a reference group; descriptive statistics comparing albiglutide and liraglutide were exploratory endpoints. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52 | Week 52 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. Clinically meaningful levels of response in HbA1c are defined as \<6.5% and \<7.0%. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline and Week 24 | FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the FPG value at Week 24 minus the FPG value at Baseline. Participants who discontinued from study treatment before Week 24 had their last post-Baseline FPG observation carried forward for the summary unless the value was 14 days past the last dose of study drug. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Baseline and Week 52 | FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value on or before the start of treatment. Change from Baseline was calculated as the FPG value at Week 52 minus the FPG value at Baseline. |
| Change From Baseline in HbA1c at Week 52 | Baseline and Week 52 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3- month period. The Baseline HbA1c value is defined as the last non-missing value on or before the start of treatment. Change from Baseline was calculated as the value at Week 52 minus the value at Baseline. |
| Change From Baseline in Body Weight at Week 52 | Baseline and Week 52 | The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 52 minus the value at Baseline. |
| Time to Study Withdrawal Due to Hyperglycemia | Baseline through Week 52 | Participants who experienced persistent hyperglycemia after uptitration were to be withdrawn from the study. Hyperglycemia is defined as a fasting plasma glucose (FPG) ≥280 mg/dL (≥15.5 mmol/L) from ≥Week 2 to \<Week 4, ≥250 mg/dL (≥13.9 mmol/L) from ≥Week 4 to \<Week 12, or ≥230 mg/dL (≥12.8 mmol/L) from ≥Week 12 to \<Week 52, confirmed a second evaluation within 7 days. |
| Time to Study Withdrawal for Any Reason | Baseline through Week 52 | Time to withdrawal was calculated as the number of days between the date of first dose and the date of withdrawal plus 1. Time to withdrawal was summarized by visit. |
| Change From Baseline in Body Weight at Week 24 | Baseline and Week 24 | The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 24 minus the value at Baseline. Participants who discontinued from the study treatment before Week 24 had their last non-missing weight carried forward for the summary, unless the value is past 14 days after the last dose of study drug. |
| Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24 | Week 24 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. Clinically meaningful levels of response in HbA1c are defined as \<6.5% and \<7.0%. Participants who discontinued the study before Week 24 had their last post-Baseline HbA1c value carried forwrad for the summary unless the value was past 14 days after the last dose of study drug. |
Countries
Japan
Participant flow
Recruitment details
A total of 494 participants (par.) were randomized to one of the four treatment groups - placebo (switched to albiglutide 30 mg at Week 24), albiglutide 30 mg, albiglutide 50 mg, liraglutide (open label), 490 par. took at least one dose of study drug (Safety Population). All 490 par. were included in Intent-to-Treat Population.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received double blind matching albiglutide placebo as a subcutaneous injection weekly to Week 24. After Week 24, participants received albiglutide 30 mg as a subcutaneous injection weekly to Week 52. | 77 |
| Albiglutide 30 mg Weekly Participants received double-blind albiglutide 30 mg as a subcutaneous injection weekly to Week 52. | 160 |
| Albiglutide 50 mg Weekly Participants received double blind albiglutide 30 mg as a subcutaneous injection weekly until Week 4. Starting at Week 4, participants received albiglutide 50 mg as a subcutaneous injection weekly to Week 52. | 150 |
| Open Label Liraglutide 0.9 mg Daily Participants received open label liraglutide as a subcutaneous injection daily at a dose of 0.3 mg with weekly forced uptitrations to a dose of 0.6 mg then a dose of 0.9 mg (maximum dose in Japan). The dose of 0.9 mg daily was given to Week 52. | 103 |
| Total | 490 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 7 | 8 | 1 |
| Overall Study | Intro of New Anti-Diabetic Medication | 4 | 0 | 0 | 1 |
| Overall Study | Inv Decision, HbA1c not controlled | 1 | 1 | 0 | 1 |
| Overall Study | Non-compliance | 1 | 0 | 0 | 0 |
| Overall Study | Persistent Hyperglycemia | 3 | 2 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 5 | 3 |
Baseline characteristics
| Characteristic | Placebo | Albiglutide 30 mg Weekly | Albiglutide 50 mg Weekly | Open Label Liraglutide 0.9 mg Daily | Total |
|---|---|---|---|---|---|
| Age, Continuous | 57.3 Years STANDARD_DEVIATION 11.27 | 59.6 Years STANDARD_DEVIATION 9 | 57.7 Years STANDARD_DEVIATION 9.51 | 58.4 Years STANDARD_DEVIATION 9.72 | 58.4 Years STANDARD_DEVIATION 9.7 |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 77 Participants | 160 Participants | 150 Participants | 103 Participants | 490 Participants |
| Sex: Female, Male Female | 25 Participants | 35 Participants | 36 Participants | 22 Participants | 118 Participants |
| Sex: Female, Male Male | 52 Participants | 125 Participants | 114 Participants | 81 Participants | 372 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 77 | 24 / 65 | 85 / 160 | 76 / 150 | 46 / 103 |
| serious Total, serious adverse events | 0 / 77 | 0 / 65 | 5 / 160 | 6 / 150 | 0 / 103 |
Outcome results
Primary
Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. The Baseline HbA1c value is defined as the last nonmissing value before the start of treatment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. Participants who discontinued from study treatment before Week 24 had their last post-Baseline HbA1c value carried forward for the summary, unless the value was past 14 days after the last dose of study drug. The open-label liraglutide group was a reference group; descriptive statistics comparing albiglutide and liraglutide were exploratory endpoints.
Time frame: Baseline and Week 24
Population: Intent-to-Treat Population (Last Observation Carried Forward): all randomized participants who received at least 1 dose of study treatment and had a Baseline assessment and at least 1 post-Baseline assessment of HbA1c on or before Week 24 provided it was not past more than 14 days after the last dose of study drug intake.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Baseline | 8.16 Percentage of HbA1c in the blood | Standard Deviation 0.877 |
| Placebo | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Change from Baseline | 0.24 Percentage of HbA1c in the blood | Standard Deviation 0.715 |
| Placebo | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Week 24 | 8.39 Percentage of HbA1c in the blood | Standard Deviation 1.066 |
| Albiglutide 30 mg Weekly | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Baseline | 8.06 Percentage of HbA1c in the blood | Standard Deviation 0.783 |
| Albiglutide 30 mg Weekly | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Change from Baseline | -1.08 Percentage of HbA1c in the blood | Standard Deviation 0.619 |
| Albiglutide 30 mg Weekly | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Week 24 | 6.98 Percentage of HbA1c in the blood | Standard Deviation 0.735 |
| Albiglutide 50 mg Weekly | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Week 24 | 6.83 Percentage of HbA1c in the blood | Standard Deviation 0.659 |
| Albiglutide 50 mg Weekly | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Baseline | 8.15 Percentage of HbA1c in the blood | Standard Deviation 0.825 |
| Albiglutide 50 mg Weekly | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Change from Baseline | -1.32 Percentage of HbA1c in the blood | Standard Deviation 0.702 |
| Open-Label Liraglutide 0.9 mg Daily | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Baseline | 8.07 Percentage of HbA1c in the blood | Standard Deviation 0.787 |
| Open-Label Liraglutide 0.9 mg Daily | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Change from Baseline | -1.19 Percentage of HbA1c in the blood | Standard Deviation 0.636 |
| Open-Label Liraglutide 0.9 mg Daily | Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24 | Week 24 | 6.87 Percentage of HbA1c in the blood | Standard Deviation 0.642 |
Primary
Model-adjusted Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. The Baseline HbA1c value is defined as the last nonmissing value before the start of treatment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. Based on analysis of covariance (ANCOVA): Change at Week 24 = treatment (placebo, albiglutide 30 mg, albiglutide 50 mg) + Baseline HbA1c + prior diabetes therapy + age category (\<65 years versus ≥65 years). Participants who discontinued from study treatment before Week 24 had their last post-Baseline HbA1c carried forward for the analysis unless the value is past 14 days after the last dose of study drug. The open-label liraglutide group was a reference group and not included in the primary endpoint analysis model. Descriptive summary statistics are provided as a separate outcome measure.
Time frame: Baseline and Week 24
Population: Intent-to-Treat Population (Last Observation Carried Forward): all randomized participants who received at least 1 dose of study treatment and had a Baseline HbA1c assessment and at least one post-Baseline HbA1c assessment of HbA1c.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Model-adjusted Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | 0.25 Percentage of HbA1c in the blood | Standard Error 0.068 |
| Albiglutide 30 mg Weekly | Model-adjusted Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -1.10 Percentage of HbA1c in the blood | Standard Error 0.047 |
| Albiglutide 50 mg Weekly | Model-adjusted Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -1.30 Percentage of HbA1c in the blood | Standard Error 0.049 |
95% CI: [-1.72, -1.39]ANCOVA
95% CI: [-1.51, -1.18]ANCOVA
p-value: <0.0001t-test, 2 sided
p-value: <0.0001t-test, 2 sided
Secondary
Change From Baseline in Body Weight at Week 24
The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 24 minus the value at Baseline. Participants who discontinued from the study treatment before Week 24 had their last non-missing weight carried forward for the summary, unless the value is past 14 days after the last dose of study drug.
Time frame: Baseline and Week 24
Population: Intent-to-Treat (Last Observation Carried Forward) Population: all randomized participants who received at least 1 dose of study treatment and had a Baseline HbA1c assessment and at least one post-Baseline HbA1c assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at Week 24 | Baseline | 68.65 Kilograms (kg) | Standard Deviation 12.088 |
| Placebo | Change From Baseline in Body Weight at Week 24 | Change from Baseline at Week 24 | -0.50 Kilograms (kg) | Standard Deviation 1.7 |
| Placebo | Change From Baseline in Body Weight at Week 24 | Week 24 | 68.15 Kilograms (kg) | Standard Deviation 12.139 |
| Albiglutide 30 mg Weekly | Change From Baseline in Body Weight at Week 24 | Baseline | 69.46 Kilograms (kg) | Standard Deviation 13.453 |
| Albiglutide 30 mg Weekly | Change From Baseline in Body Weight at Week 24 | Change from Baseline at Week 24 | 0.32 Kilograms (kg) | Standard Deviation 1.795 |
| Albiglutide 30 mg Weekly | Change From Baseline in Body Weight at Week 24 | Week 24 | 69.78 Kilograms (kg) | Standard Deviation 13.793 |
| Albiglutide 50 mg Weekly | Change From Baseline in Body Weight at Week 24 | Week 24 | 71.50 Kilograms (kg) | Standard Deviation 13.023 |
| Albiglutide 50 mg Weekly | Change From Baseline in Body Weight at Week 24 | Baseline | 71.54 Kilograms (kg) | Standard Deviation 12.907 |
| Albiglutide 50 mg Weekly | Change From Baseline in Body Weight at Week 24 | Change from Baseline at Week 24 | -0.04 Kilograms (kg) | Standard Deviation 1.976 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Body Weight at Week 24 | Baseline | 72.65 Kilograms (kg) | Standard Deviation 13.758 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Body Weight at Week 24 | Change from Baseline at Week 24 | -0.34 Kilograms (kg) | Standard Deviation 2.587 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Body Weight at Week 24 | Week 24 | 72.30 Kilograms (kg) | Standard Deviation 13.459 |
Secondary
Change From Baseline in Body Weight at Week 52
The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 52 minus the value at Baseline.
Time frame: Baseline and Week 52
Population: Intent-to-Treat (Observed Case) Population: all randomized participants who received at least 1 dose of study treatment and had a Baseline HbA1c assessment and at least one post-Baseline HbA1c assessment. Participants who discontinued before Week 52 from study treatment were not included in the analysis. No missing data were imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at Week 52 | Baseline | 68.07 Kilograms (kg) | Standard Deviation 11.978 |
| Placebo | Change From Baseline in Body Weight at Week 52 | Change from Baseline at Week 52 | -0.07 Kilograms (kg) | Standard Deviation 2.179 |
| Placebo | Change From Baseline in Body Weight at Week 52 | Week 52 | 68.00 Kilograms (kg) | Standard Deviation 12.15 |
| Albiglutide 30 mg Weekly | Change From Baseline in Body Weight at Week 52 | Baseline | 70.07 Kilograms (kg) | Standard Deviation 13.242 |
| Albiglutide 30 mg Weekly | Change From Baseline in Body Weight at Week 52 | Change from Baseline at Week 52 | 0.08 Kilograms (kg) | Standard Deviation 2.078 |
| Albiglutide 30 mg Weekly | Change From Baseline in Body Weight at Week 52 | Week 52 | 70.15 Kilograms (kg) | Standard Deviation 13.536 |
| Albiglutide 50 mg Weekly | Change From Baseline in Body Weight at Week 52 | Week 52 | 70.96 Kilograms (kg) | Standard Deviation 12.431 |
| Albiglutide 50 mg Weekly | Change From Baseline in Body Weight at Week 52 | Baseline | 71.27 Kilograms (kg) | Standard Deviation 12.801 |
| Albiglutide 50 mg Weekly | Change From Baseline in Body Weight at Week 52 | Change from Baseline at Week 52 | -0.31 Kilograms (kg) | Standard Deviation 2.382 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Body Weight at Week 52 | Baseline | 72.43 Kilograms (kg) | Standard Deviation 12.895 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Body Weight at Week 52 | Change from Baseline at Week 52 | -0.50 Kilograms (kg) | Standard Deviation 2.69 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Body Weight at Week 52 | Week 52 | 71.93 Kilograms (kg) | Standard Deviation 12.564 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the FPG value at Week 24 minus the FPG value at Baseline. Participants who discontinued from study treatment before Week 24 had their last post-Baseline FPG observation carried forward for the summary unless the value was 14 days past the last dose of study drug.
Time frame: Baseline and Week 24
Population: Intent-to-Treat (Last Observation Carried Forward) Population: all randomized participants who received at least 1 dose of study treatment and had a Baseline HbA1c assessment and at least one post-Baseline HbA1c assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline | 159.3 Milligrams per deciliter (mg/dL) | Standard Deviation 37.07 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Change from Baseline at Week 24 | 7.7 Milligrams per deciliter (mg/dL) | Standard Deviation 31.77 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 | 167.0 Milligrams per deciliter (mg/dL) | Standard Deviation 37.51 |
| Albiglutide 30 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline | 157.1 Milligrams per deciliter (mg/dL) | Standard Deviation 33.81 |
| Albiglutide 30 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Change from Baseline at Week 24 | -24.9 Milligrams per deciliter (mg/dL) | Standard Deviation 27.58 |
| Albiglutide 30 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 | 132.2 Milligrams per deciliter (mg/dL) | Standard Deviation 26.09 |
| Albiglutide 50 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 | 128.8 Milligrams per deciliter (mg/dL) | Standard Deviation 24.03 |
| Albiglutide 50 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline | 158.7 Milligrams per deciliter (mg/dL) | Standard Deviation 32.82 |
| Albiglutide 50 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Change from Baseline at Week 24 | -30.0 Milligrams per deciliter (mg/dL) | Standard Deviation 27.83 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline | 157.2 Milligrams per deciliter (mg/dL) | Standard Deviation 31.22 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Change from Baseline at Week 24 | -29.1 Milligrams per deciliter (mg/dL) | Standard Deviation 29 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Week 24 | 128.1 Milligrams per deciliter (mg/dL) | Standard Deviation 23.68 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52
FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value on or before the start of treatment. Change from Baseline was calculated as the FPG value at Week 52 minus the FPG value at Baseline.
Time frame: Baseline and Week 52
Population: Intent-to-Treat (Observed Case) Population: all randomized participants who received at least 1 dose of study treatment and had a Baseline HbA1c assessment and at least one post-Baseline HbA1c assessment. Participants who discontinued from study treatment before Week 52 were not included in this analysis. No missing data were imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Change from Baseline at Week 52 | -22.7 Milligrams per deciliter (mg/dL) | Standard Deviation 27.38 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Baseline | 154.5 Milligrams per deciliter (mg/dL) | Standard Deviation 35.65 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Week 52 | 131.7 Milligrams per deciliter (mg/dL) | Standard Deviation 23.13 |
| Albiglutide 30 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Baseline | 154.7 Milligrams per deciliter (mg/dL) | Standard Deviation 29.36 |
| Albiglutide 30 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Change from Baseline at Week 52 | -22.8 Milligrams per deciliter (mg/dL) | Standard Deviation 26.03 |
| Albiglutide 30 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Week 52 | 131.9 Milligrams per deciliter (mg/dL) | Standard Deviation 24.14 |
| Albiglutide 50 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Week 52 | 126.3 Milligrams per deciliter (mg/dL) | Standard Deviation 24.47 |
| Albiglutide 50 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Baseline | 159.8 Milligrams per deciliter (mg/dL) | Standard Deviation 33.52 |
| Albiglutide 50 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Change from Baseline at Week 52 | -33.5 Milligrams per deciliter (mg/dL) | Standard Deviation 31.1 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Baseline | 157.4 Milligrams per deciliter (mg/dL) | Standard Deviation 30.27 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Change from Baseline at Week 52 | -30.4 Milligrams per deciliter (mg/dL) | Standard Deviation 28.06 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Week 52 | 127.0 Milligrams per deciliter (mg/dL) | Standard Deviation 20.78 |
Secondary
Change From Baseline in HbA1c at Week 52
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3- month period. The Baseline HbA1c value is defined as the last non-missing value on or before the start of treatment. Change from Baseline was calculated as the value at Week 52 minus the value at Baseline.
Time frame: Baseline and Week 52
Population: Intent-to-Treat (Observed Case) Population: all randomized participants who received at least 1 dose of study treatment and had a Baseline HbA1c assessment and at least one post-Baseline HbA1c assessment. Participants who discontinued from study treatment before Week 52 were not included in the analysis. No missing data were imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c at Week 52 | -1.07 Percentage of HbA1c in the blood | Standard Deviation 0.695 |
| Albiglutide 30 mg Weekly | Change From Baseline in HbA1c at Week 52 | -1.07 Percentage of HbA1c in the blood | Standard Deviation 0.79 |
| Albiglutide 50 mg Weekly | Change From Baseline in HbA1c at Week 52 | -1.34 Percentage of HbA1c in the blood | Standard Deviation 0.753 |
| Open-Label Liraglutide 0.9 mg Daily | Change From Baseline in HbA1c at Week 52 | -1.17 Percentage of HbA1c in the blood | Standard Deviation 0.776 |
Secondary
Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. Clinically meaningful levels of response in HbA1c are defined as \<6.5% and \<7.0%. Participants who discontinued the study before Week 24 had their last post-Baseline HbA1c value carried forwrad for the summary unless the value was past 14 days after the last dose of study drug.
Time frame: Week 24
Population: Intent-to-Treat (Last Observation Carried Forward) Population: all randomized participants who received at least 1 dose of study treatment and had a Baseline HbA1c assessment and at least one post-Baseline HbA1c assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24 | HbA1c <6.5% at Week 24 | 1 Percentage of participants |
| Placebo | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24 | HbA1c <7.0% at Week 24 | 4 Percentage of participants |
| Albiglutide 30 mg Weekly | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24 | HbA1c <7.0% at Week 24 | 92 Percentage of participants |
| Albiglutide 30 mg Weekly | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24 | HbA1c <6.5% at Week 24 | 31 Percentage of participants |
| Albiglutide 50 mg Weekly | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24 | HbA1c <6.5% at Week 24 | 47 Percentage of participants |
| Albiglutide 50 mg Weekly | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24 | HbA1c <7.0% at Week 24 | 100 Percentage of participants |
| Open-Label Liraglutide 0.9 mg Daily | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24 | HbA1c <6.5% at Week 24 | 29 Percentage of participants |
| Open-Label Liraglutide 0.9 mg Daily | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24 | HbA1c <7.0% at Week 24 | 66 Percentage of participants |
Secondary
Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. Clinically meaningful levels of response in HbA1c are defined as \<6.5% and \<7.0%.
Time frame: Week 52
Population: Intent-to-Treat (Observed Case) Population: all randomized participants who received at least 1 dose of study treatment and had a Baseline HbA1c assessment and at least one post-Baseline HbA1c assessment. Participants who discontinued from study treatment before Week 52 were not included in the analysis. No missing data were imputed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52 | HbA1c <6.5% at Week 52 | 14 Percentage of participants |
| Placebo | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52 | HbA1c <7.0% at Week 52 | 33 Percentage of participants |
| Albiglutide 30 mg Weekly | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52 | HbA1c <7.0% at Week 52 | 82 Percentage of participants |
| Albiglutide 30 mg Weekly | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52 | HbA1c <6.5% at Week 52 | 44 Percentage of participants |
| Albiglutide 50 mg Weekly | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52 | HbA1c <6.5% at Week 52 | 53 Percentage of participants |
| Albiglutide 50 mg Weekly | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52 | HbA1c <7.0% at Week 52 | 85 Percentage of participants |
| Open-Label Liraglutide 0.9 mg Daily | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52 | HbA1c <6.5% at Week 52 | 27 Percentage of participants |
| Open-Label Liraglutide 0.9 mg Daily | Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52 | HbA1c <7.0% at Week 52 | 57 Percentage of participants |
Secondary
Time to Study Withdrawal Due to Hyperglycemia
Participants who experienced persistent hyperglycemia after uptitration were to be withdrawn from the study. Hyperglycemia is defined as a fasting plasma glucose (FPG) ≥280 mg/dL (≥15.5 mmol/L) from ≥Week 2 to \<Week 4, ≥250 mg/dL (≥13.9 mmol/L) from ≥Week 4 to \<Week 12, or ≥230 mg/dL (≥12.8 mmol/L) from ≥Week 12 to \<Week 52, confirmed a second evaluation within 7 days.
Time frame: Baseline through Week 52
Population: Intent-to-Treat Population: all randomized par. who received at least 1 dose of study treatment and had a Baseline HbA1c assessment and at least one post-Baseline HbA1c assessment. Par. who did not conform to the protocol-defined criteria of persistent hyperglycemia with respect to FPG values defined above were not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Study Withdrawal Due to Hyperglycemia | NA Weeks |
| Albiglutide 30 mg Weekly | Time to Study Withdrawal Due to Hyperglycemia | NA Weeks |
| Albiglutide 50 mg Weekly | Time to Study Withdrawal Due to Hyperglycemia | NA Weeks |
| Open-Label Liraglutide 0.9 mg Daily | Time to Study Withdrawal Due to Hyperglycemia | NA Weeks |
Secondary
Time to Study Withdrawal for Any Reason
Time to withdrawal was calculated as the number of days between the date of first dose and the date of withdrawal plus 1. Time to withdrawal was summarized by visit.
Time frame: Baseline through Week 52
Population: Intent-to-Treat Population: all randomized participants who received at least 1 dose of study treatment and had a Baseline assessment and at least one post-Baseline assessment (scheduled or unscheduled) of the primary endpoint, HbA1c.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Study Withdrawal for Any Reason | NA Weeks |
| Albiglutide 30 mg Weekly | Time to Study Withdrawal for Any Reason | NA Weeks |
| Albiglutide 50 mg Weekly | Time to Study Withdrawal for Any Reason | NA Weeks |
| Open-Label Liraglutide 0.9 mg Daily | Time to Study Withdrawal for Any Reason | NA Weeks |