Diabetes Mellitus, Type 2
Conditions
Keywords
dose-ranging, pharmacokinetics, GSK716155, Japan, albiglutide
Brief summary
This is a randomized, double-blind, placebo-controlled, multicenter, 4-parallel-group, dose ranging study evaluating the dose response, efficacy and safety of subcutaneously injected GSK716155 (albiglutide) in Japanese subjects with type 2 diabetes mellitus.
Detailed description
This is a Phase IIb, randomized, double-blind, placebo-controlled, multicenter, 4-parallel-group, dose ranging, superiority study evaluating the dose response, efficacy and safety of weekly and every other week subcutaneously injected GSK716155 (albiglutide) in subjects with type 2 diabetes mellitus.
Interventions
BIOLOGICALalbiglutide
subcutaneous injection of albiglutide
BIOLOGICALplacebo
subcutaneous injection of placebo to match albiglutide
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject with a historical diagnosis of type 2 diabetes mellitus who is currently treated with diet and exercise only or one OAD * BMI ≥18 kg/m2 and \<35 kg/m2 at Screening * HbA1c between 7.0% and 10.0%, inclusive * Fasting C-peptide ≥0.8 ng/mL (≥0.26 nmol/L) * Female subjects of childbearing potential must be practicing adequate contraception . * Able and willing to monitor his/her own blood glucose concentrations with a home glucose monitor. * Able and willing to provide written informed consent
Exclusion criteria
* Diagnosis of type 1 diabetes mellitus * Uncorrected thyroid dysfunction * Previous use of insulin within one month prior to screening, or more than seven total days of insulin treatment within three months prior to screening * Clinically significantly cardiovascular and/or cerebrovascular disease including, but not limited to the following: * Previous history of stroke or transient ischemic attack * Active, unstable coronary heart disease within the past six months before Screening * Documented myocardial infarction within one year before Screening * Any cardiac surgery including percutaneous transluminal coronary angioplasty, coronary stent placement, or coronary artery bypass graft surgery within one year before Screening * Unstable angina * Clinically significant arrhythmia or valvular heart disease * Current heart failure NYHA class II to IV * Resting systolic pressure \>160 mm Hg or diastolic pressure \>95 mm Hg at Screening * ECG criteria at Screening * Heart rate: \<40 and \>110 bpm * PR interval: \<120 and \> 210 msec * QRS interval: \<70 and \>120 msec * QTc interval (Bazett): \>450 msec or \>480 msec with bundle branch block * Fasting triglyceride level \>400 mg/dL at Screening * AST or ALT \>2xULN, ALP and bilirubin \>1.5xULN (except known Gilbert's syndrome and a fractionated bilirubin that shows conjugated bilirubin \<35% of total bilirubin) * If female, is currently lactating, within 6 weeks post-partum, pregnant, or actively trying to become pregnant * Has significant renal disease as manifested by one or more of the following: * Creatinine clearance at screening \<60 mL/min (calculated by Cockcroft-Gault formula) at Screening * Known loss of a kidney either by surgical ablation, injury or disease level * A hemoglobinopathy that may affect determination of HbA1c level * History of treated diabetic gastroparesis * History of significant gastrointestinal surgery, including gastric bypass and banding, or surgeries thought to significantly affect upper gastrointestinal function * Current ongoing symptomatic biliary disease or history of acute/chronic pancreatitis. * Lipase and amylase at Screening \> ULN * Severe diabetic neuropathy, preproliferative retinopathy or proliferative retinopathy, history of ketoacidosis or hyperosmolar coma * History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 3 years before Screening. (A history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed) * Acute or chronic history of liver disease, positive hepatitis B surface antigen (HBsAg) or positive hepatitis C testing at Screening * Current and history of alcohol or substance abuse * Clinically significant anaemia or any other abnormal haematological profile that is considered by the investigator to be clinically significant * Prior use of a GLP-1 analog * Known allergy to any formulation excipients, or Baker's yeast, or history of drug, or other allergy which, in the opinion of the responsible study physician, contradicts participation * History of or family history of medullary carcinoma of the thyroid. * History of or family history of multiple endocrine neoplasia type 2 * Receipt of any investigational drug within the 12 weeks before Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16 | Baseline and Week 16 | 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 before the start of treatment. Change from Baseline was calculated as the value at Week 16 minus the value at Baseline. Based on Analysis of Covariance (ANCOVA): Change = treatment + Baseline HbA1c + prior therapy. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Baseline; Week 4, Week 8, Week 12, and Week 16 | The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. The LOCF method was used to impute missing post-Baseline FPG values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Baseline; Week 4, Week 8, Week 12, and Week 16 | The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. The LOCF method was used to impute missing post-Baseline weight values. |
| Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | Week 4, Week 8, Week 12, and Week 16 | The number of participants who achieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5% and \<7%) were assessed. |
| Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Baseline; Week 4, Week 8, Week 12, and Week 16 | 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 before the start of treatment. Change from Baseline was calculated as the value at Week 16 minus the value at Baseline. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing. |
| Mean Volume of Distribution of Albiglutide | Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24 | Volume of distribution is defined as the apparent volume in which albiglutide is distributed. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK. |
| Mean Absorption Rate of Albiglutide | Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24 | Absorption rate is defined as the rate at which albiglutide enters the blood circulation. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK. |
| Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG | Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24 | EC50 is defined as the concentration of albiglutide that give a half-maximal HbA1c and FPG response. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. EC50 estimates used PK data as well as HbA1c and FPG efficacy data. EC50 was estimated from an inhibitory Emax (maximal possible effect of albiglutide) model. |
| Mean Clearance of Albiglutide | Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24 | Clearance is defined as the volume of plasma cleared of albiglutide per unit time. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, pharmacokinetic (PK) samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK. |
Countries
Japan
Participant flow
Pre-assignment details
Participants (par.) who met eligibility criteria and completed a 4- to 8-week Run-in Period were then randomized to a 16-week Treatment Period, followed by an 8-week Follow-up Period. A total of 215 participants were randomized, and 212 received \>=1 treatment dose.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received albiglutide-matching placebo administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion. | 53 |
| Albiglutide 15 mg Weekly Participants received albiglutide 15 milligrams (mg) administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion. | 52 |
| Albiglutide 30 mg Weekly Participants received albiglutide 30 mg administered via subcutaneous injection once a week via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion. | 54 |
| Albiglutide 30 mg Every Other Week Participants received albiglutide 30 mg or matching placebo administered via subcutaneous injection on alternating weeks via a fully disposable pen injector system for 16 weeks. The preferred post-rescue add-on treatment was insulin. Other medications may have been added at the investigator's discretion. | 53 |
| Total | 212 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-up (FU) Period (8 Weeks) | Follow-up Not Conducted Due to Earthquak | 0 | 1 | 1 | 0 |
| Follow-up (FU) Period (8 Weeks) | Transferred to Oita (Japan) | 0 | 1 | 0 | 0 |
| Follow-up (FU) Period (8 Weeks) | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Treatment Period (TP) (16 Weeks) | Adverse Event | 1 | 2 | 1 | 3 |
| Treatment Period (TP) (16 Weeks) | Persistent Hypoglycemia | 10 | 2 | 0 | 0 |
| Treatment Period (TP) (16 Weeks) | Transferred to Oita (Japan) | 0 | 1 | 0 | 0 |
| Treatment Period (TP) (16 Weeks) | Withdrawal by Subject | 1 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Albiglutide 15 mg Weekly | Albiglutide 30 mg Weekly | Albiglutide 30 mg Every Other Week | Total |
|---|---|---|---|---|---|
| Age, Continuous | 57.5 Years STANDARD_DEVIATION 11.06 | 53.3 Years STANDARD_DEVIATION 10.29 | 58.0 Years STANDARD_DEVIATION 9.3 | 59.1 Years STANDARD_DEVIATION 8.49 | 57.0 Years STANDARD_DEVIATION 10 |
| Gender Female | 16 Participants | 20 Participants | 16 Participants | 12 Participants | 64 Participants |
| Gender Male | 37 Participants | 32 Participants | 38 Participants | 41 Participants | 148 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 53 participants | 52 participants | 54 participants | 53 participants | 212 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 53 | 27 / 52 | 20 / 54 | 23 / 53 |
| serious Total, serious adverse events | 2 / 53 | 1 / 52 | 2 / 54 | 2 / 53 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16
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 before the start of treatment. Change from Baseline was calculated as the value at Week 16 minus the value at Baseline. Based on Analysis of Covariance (ANCOVA): Change = treatment + Baseline HbA1c + prior therapy. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.
Time frame: Baseline and Week 16
Population: Intent-to-Treat (ITT) Population: all randomized participants with at least one post-Baseline assessment of the primary endpoint, HbA1c. Only those participants with a value available at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were discontinued from active treatment before Week 16.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16 | 0.28 Percentage of HbA1c in the blood | Standard Error 0.099 |
| Albiglutide 15 mg Weekly | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16 | -0.61 Percentage of HbA1c in the blood | Standard Error 0.097 |
| Albiglutide 30 mg Weekly | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16 | -1.27 Percentage of HbA1c in the blood | Standard Error 0.095 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16 | -0.82 Percentage of HbA1c in the blood | Standard Error 0.096 |
p-value: <0.000195% CI: [-1.22, -0.57]t-test, 2 sided
p-value: <0.000195% CI: [-1.88, -1.23]t-test, 2 sided
p-value: <0.000195% CI: [-1.43, -0.78]t-test, 2 sided
Secondary
Change From Baseline in Body Weight at Week 4, 8, 12, and 16
The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. The LOCF method was used to impute missing post-Baseline weight values.
Time frame: Baseline; Week 4, Week 8, Week 12, and Week 16
Population: ITT Population with LOCF. Only those participants with a value available at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were discontinued from active treatment before Week 16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 4 | -0.16 Kilograms | Standard Deviation 0.956 |
| Placebo | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 8 | -0.29 Kilograms | Standard Deviation 1.289 |
| Placebo | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 12 | -0.43 Kilograms | Standard Deviation 1.409 |
| Placebo | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 16 | -0.65 Kilograms | Standard Deviation 1.715 |
| Albiglutide 15 mg Weekly | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 8 | -0.06 Kilograms | Standard Deviation 0.926 |
| Albiglutide 15 mg Weekly | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 12 | 0.09 Kilograms | Standard Deviation 1.277 |
| Albiglutide 15 mg Weekly | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 16 | 0.43 Kilograms | Standard Deviation 1.468 |
| Albiglutide 15 mg Weekly | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 4 | -0.36 Kilograms | Standard Deviation 0.752 |
| Albiglutide 30 mg Weekly | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 12 | -0.20 Kilograms | Standard Deviation 1.906 |
| Albiglutide 30 mg Weekly | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 8 | -0.46 Kilograms | Standard Deviation 1.671 |
| Albiglutide 30 mg Weekly | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 16 | -0.20 Kilograms | Standard Deviation 1.977 |
| Albiglutide 30 mg Weekly | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 4 | -0.25 Kilograms | Standard Deviation 1.268 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 16 | -0.08 Kilograms | Standard Deviation 1.74 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 8 | -0.25 Kilograms | Standard Deviation 1.684 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 4 | -0.02 Kilograms | Standard Deviation 1.12 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in Body Weight at Week 4, 8, 12, and 16 | Week 12 | -0.22 Kilograms | Standard Deviation 1.459 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16
The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. The LOCF method was used to impute missing post-Baseline FPG values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; Week 4, Week 8, Week 12, and Week 16
Population: ITT Population with LOCF. Only those participants with a value available at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were discontinued from active treatment before Week 16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 4 | 0.30 Millimoles per liter (mmol/L) | Standard Deviation 1.19 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 8 | 0.41 Millimoles per liter (mmol/L) | Standard Deviation 1.451 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 12 | 0.38 Millimoles per liter (mmol/L) | Standard Deviation 1.612 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 16 | 0.50 Millimoles per liter (mmol/L) | Standard Deviation 2.448 |
| Albiglutide 15 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 8 | -1.54 Millimoles per liter (mmol/L) | Standard Deviation 1.585 |
| Albiglutide 15 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 12 | -1.25 Millimoles per liter (mmol/L) | Standard Deviation 1.511 |
| Albiglutide 15 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 16 | -0.77 Millimoles per liter (mmol/L) | Standard Deviation 1.583 |
| Albiglutide 15 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 4 | -1.54 Millimoles per liter (mmol/L) | Standard Deviation 1.378 |
| Albiglutide 30 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 12 | -1.92 Millimoles per liter (mmol/L) | Standard Deviation 1.388 |
| Albiglutide 30 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 8 | -2.27 Millimoles per liter (mmol/L) | Standard Deviation 1.652 |
| Albiglutide 30 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 16 | -1.92 Millimoles per liter (mmol/L) | Standard Deviation 1.667 |
| Albiglutide 30 mg Weekly | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 4 | -2.27 Millimoles per liter (mmol/L) | Standard Deviation 1.465 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 16 | -0.78 Millimoles per liter (mmol/L) | Standard Deviation 1.821 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 8 | -1.19 Millimoles per liter (mmol/L) | Standard Deviation 1.458 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 4 | -1.32 Millimoles per liter (mmol/L) | Standard Deviation 1.271 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 | Week 12 | -1.06 Millimoles per liter (mmol/L) | Standard Deviation 1.555 |
Secondary
Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16
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 before the start of treatment. Change from Baseline was calculated as the value at Week 16 minus the value at Baseline. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.
Time frame: Baseline; Week 4, Week 8, Week 12, and Week 16
Population: ITT Population with LOCF. Only those participants with a value available at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were discontinued from active treatment before Week 16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 8 | 0.20 Percentage of HbA1c in the blood | Standard Deviation 0.628 |
| Placebo | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 12 | 0.24 Percentage of HbA1c in the blood | Standard Deviation 0.73 |
| Placebo | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 16 | 0.27 Percentage of HbA1c in the blood | Standard Deviation 0.743 |
| Placebo | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 4 | 0.03 Percentage of HbA1c in the blood | Standard Deviation 0.349 |
| Albiglutide 15 mg Weekly | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 4 | -0.33 Percentage of HbA1c in the blood | Standard Deviation 0.301 |
| Albiglutide 15 mg Weekly | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 16 | -0.63 Percentage of HbA1c in the blood | Standard Deviation 0.548 |
| Albiglutide 15 mg Weekly | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 8 | -0.59 Percentage of HbA1c in the blood | Standard Deviation 0.43 |
| Albiglutide 15 mg Weekly | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 12 | -0.71 Percentage of HbA1c in the blood | Standard Deviation 0.464 |
| Albiglutide 30 mg Weekly | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 4 | -0.61 Percentage of HbA1c in the blood | Standard Deviation 0.377 |
| Albiglutide 30 mg Weekly | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 16 | -1.29 Percentage of HbA1c in the blood | Standard Deviation 0.736 |
| Albiglutide 30 mg Weekly | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 12 | -1.26 Percentage of HbA1c in the blood | Standard Deviation 0.649 |
| Albiglutide 30 mg Weekly | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 8 | -1.07 Percentage of HbA1c in the blood | Standard Deviation 0.578 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 16 | -0.84 Percentage of HbA1c in the blood | Standard Deviation 0.875 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 4 | -0.36 Percentage of HbA1c in the blood | Standard Deviation 0.383 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 8 | -0.74 Percentage of HbA1c in the blood | Standard Deviation 0.618 |
| Albiglutide 30 mg Every Other Week | Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 | Week 12 | -0.84 Percentage of HbA1c in the blood | Standard Deviation 0.72 |
Secondary
Mean Absorption Rate of Albiglutide
Absorption rate is defined as the rate at which albiglutide enters the blood circulation. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK.
Time frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
Population: PK Analysis Population (Pop)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Mean Absorption Rate of Albiglutide | 0.0154 hour^-1 |
Secondary
Mean Clearance of Albiglutide
Clearance is defined as the volume of plasma cleared of albiglutide per unit time. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, pharmacokinetic (PK) samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK.
Time frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
Population: PK Analysis Population: all participants for whom a PK sample was obtained and analyzed
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Mean Clearance of Albiglutide | 47.8 milliliters per hour |
Secondary
Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG
EC50 is defined as the concentration of albiglutide that give a half-maximal HbA1c and FPG response. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. EC50 estimates used PK data as well as HbA1c and FPG efficacy data. EC50 was estimated from an inhibitory Emax (maximal possible effect of albiglutide) model.
Time frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
Population: PK/PD Analysis Pop: all participants in the PK Analysis Pop with sufficient dosing history for inclusion in the PK/PD analysis. Modeled population PK data (analyzed using a non-linear mixed effect modeling approach) are presented. A one-compartment PK model with first-order absorption/elimination processes was selected to describe GSK716155 PK.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG | HbA1c | 3360 nanograms per milliliter |
| Placebo | Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG | FPG | 3850 nanograms per milliliter |
Secondary
Mean Volume of Distribution of Albiglutide
Volume of distribution is defined as the apparent volume in which albiglutide is distributed. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK.
Time frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
Population: PK Analysis Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Mean Volume of Distribution of Albiglutide | 9.34 Liters |
Secondary
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16
The number of participants who achieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5% and \<7%) were assessed.
Time frame: Week 4, Week 8, Week 12, and Week 16
Population: ITT Population with LOCF. Only those participants with a value available at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were discontinued from active treatment before Week 16.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 4 | 0 Participants |
| Placebo | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 8 | 0 Participants |
| Placebo | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 12 | 0 Participants |
| Placebo | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 16 | 0 Participants |
| Placebo | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 4 | 2 Participants |
| Placebo | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 8 | 4 Participants |
| Placebo | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 12 | 3 Participants |
| Placebo | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 16 | 3 Participants |
| Albiglutide 15 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 8 | 12 Participants |
| Albiglutide 15 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 4 | 7 Participants |
| Albiglutide 15 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 8 | 5 Participants |
| Albiglutide 15 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 16 | 9 Participants |
| Albiglutide 15 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 12 | 12 Participants |
| Albiglutide 15 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 16 | 5 Participants |
| Albiglutide 15 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 12 | 6 Participants |
| Albiglutide 15 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 4 | 1 Participants |
| Albiglutide 30 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 12 | 32 Participants |
| Albiglutide 30 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 12 | 19 Participants |
| Albiglutide 30 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 16 | 18 Participants |
| Albiglutide 30 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 4 | 19 Participants |
| Albiglutide 30 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 8 | 27 Participants |
| Albiglutide 30 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 16 | 34 Participants |
| Albiglutide 30 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 4 | 2 Participants |
| Albiglutide 30 mg Weekly | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 8 | 15 Participants |
| Albiglutide 30 mg Every Other Week | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 12 | 8 Participants |
| Albiglutide 30 mg Every Other Week | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 16 | 8 Participants |
| Albiglutide 30 mg Every Other Week | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 8 | 5 Participants |
| Albiglutide 30 mg Every Other Week | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <6.5%, Week 4 | 1 Participants |
| Albiglutide 30 mg Every Other Week | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 4 | 9 Participants |
| Albiglutide 30 mg Every Other Week | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 16 | 21 Participants |
| Albiglutide 30 mg Every Other Week | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 12 | 19 Participants |
| Albiglutide 30 mg Every Other Week | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 | HbA1c <7%, Week 8 | 18 Participants |