Diabetes Mellitus, Type 2
Conditions
Keywords
Pharmacodynamics, Safety, Albiglutide, Tolerability, Type 2 Diabetes Mellitus, Efficacy
Brief summary
This is a phase III, randomized, double-blind, multicenter, parallel group, repeat-dose, study of 26 weeks duration to evaluate the efficacy, safety, tolerability and pharmacodynamic response of albiglutide liquid drug product relative to the commercial lyophilized drug product. The study will specifically evaluate the potential for immunogenicity (example \[e.g.\] incidences of anti-drug antibodies \[ADA\]) and injection site reactions (ISRs). Albiglutide is a novel analogue of glucagon-like peptide-1 (GLP-1) with a sufficiently long half-life to permit once a week injection. Currently, lyophilized albiglutide and the diluent are provided in a dual chamber cartridge (DCC), single-dose pen injector, requiring reconstitution prior to use. A liquid formulation of albiglutide will enable the commercialization of a liquid product in a single dose, ready-to-use prefilled syringe in an auto-injector. The primary hypothesis of this study is to test that liquid drug product will provide glycemic control (as measured by HbA1c change from baseline) non-inferior to lyophilized drug product for a period of 26 weeks of treatment in subjects with T2DM. This study will comprise of 3 study periods : screening (2 weeks), treatment (26 weeks) and for those subjects not entering the extension study a follow-up period (8 weeks). Approximately 300 subjects will be randomized in a 1:1 ratio to either Albiglutide active liquid auto-injector (LAI) plus Placebo lyophilized DCC pen injector (lyophilized DCC PI); or, Albiglutide lyophilized DCC PI plus Placebo LAI.
Interventions
DRUGLyophilized albiglutide DCC pen injector
A fixed-dose, fully disposable pen injector system with a prefilled dual chamber glass cartridge (DCC) containing lyophilized albiglutide (30mg or 50mg) delivering an injection volume of 0.5mL.
DRUGLyophilized albiglutide DCC pen injector matching placebo
A fixed-dose, fully disposable pen injector system with a prefilled DCC containing matching placebo delivering an injection volume of 0.5mL
A fixed-dose, single use, disposable auto-injector containing albiglutide liquid (30mg or 50mg) in a prefilled glass syringe. The auto-injector delivers the albiglutide liquid in an injection volume of 0.6 mL for the 30mg dose and 1.0 mL for the 50mg dose.
DRUGAlbiglutide liquid auto-injector matching placebo
A fixed-dose, single use, disposable auto-injector containing matching placebo in a prefilled glass syringe. The auto-injector delivers the matching placebo in an injection volume of 0.6 mL for the 30mg dose and 1.0 mL for the 50mg dose.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 80 years of age inclusive * Historical diagnosis of type 2 diabetes mellitus (T2DM) (at least 3 months), experiencing inadequate glycemic control on current regimen of diet and exercise or on a stable maximal tolerated dose of metformin, maintained for approximately 8 weeks prior to screening. * HbA1c \>=7.0 percent (%) and \<=10%. * Hemoglobin \>=11 grams per deciliter (g/dL) (\>=110 grams per liter \[g/L\]) for males and \>=10 g/dL (\>=100 g/L) for females. * Body mass index \<=40 kilograms per squared meter (kg/m\^2) * Male or female * Able and willing to provide informed consent.
Exclusion criteria
* Type 1 diabetes mellitus * History of cancer that has not been in full remission for at least 3 years before screening. (A history of squamous cell or basal cell carcinoma of the skin or treated cervical intra-epithelial neoplasia I or II is allowed). * Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. * History of acute or chronic pancreatitis. * History of thyroid dysfunction or an abnormal (i.e., outside the normal reference range) thyroid function test assessed by thyroid stimulating hormone at screening. * Severe gastroparesis, i.e., requiring regular therapy within 6 months before screening. * History of significant gastrointestinal (GI) surgery that in the opinion of the investigator is likely to significantly affect upper GI or pancreatic function * History of severe hypoglycemia unawareness * Diabetic complications or any other clinically significant abnormality . * Clinically significant Cardiovascular (CV) and/or cerebrovascular disease within 3 months before screening * QT interval corrected for heart rate according to Fridericia's formula (QTcF) \> 470 milliseconds (msec). * ALT \>2.5x upper limit of the normal range (ULN) or bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). * Estimated glomerular filtration rate (eGFR) \<=30 milliliter (mL)/minute (min)/1.73 squared meter (m\^2) (calculated using the Modification of Diet in Renal Disease \[MDRD\] formula) at screening. * Fasting triglyceride level \>750 milligrams per deciliter (mg/dL) at screening. * Hemoglobinopathy that may affect proper interpretation of HbA1c. * Medical or psychiatric disorders that would preclude effective participation in study. * Use of oral or systemically injected glucocorticoids within the 3 months before randomization or high likelihood of a requirement for prolonged treatment (\>1 week) in the 6 months following randomization. * Use of dipeptidyl peptidase-IV inhibitors within the 3 months before randomization. * History of alcohol or substance abuse within one year before screening. * Known allergy to albiglutide or any product components (including yeast and human albumin), any other glucagon-like peptide-1 (GLP-1) analogue, or other study medication's excipients OR other contraindications (per the prescribing information) for the use of potential study medications. * A positive pre-study drug/alcohol screen. * A positive test for human immunodeficiency virus (HIV) antibody. * The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26 | Baseline and Week 26 | Blood samples will be collected from participants at specific time points to evaluate HbA1c to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a mixed-effect model with repeated measures (MMRM) method. The primary analysis will include all HbA1c values collected at scheduled visits from Week 4 up to Week 26. This will include values after hyperglycemia rescue and discontinuation from investigational product. Imputation under the non-inferiority null hypothesis for missing data will be incorporated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Up to Week 26 | Chemistry parameters for which PCC values were identified were alanine aminotransferase (ALT) (if value \>3 \* upper limit of normal \[ULN\]), albumin (if value \>5 gram/liter \[g/L\] above ULN or below lower limit of normal \[LLN\]), alkaline phosphatase (alk.phosph.) (if value \>3\*ULN), aspartate aminotransferase (AST) (if value \>3\*ULN), total bilirubin (if value \>1.5 ULN), calcium (if value \<1.8 or \>3.0 millimoles per liter \[mmol/L\]), carbon di oxide (CO2) (if value \<16 or \>40 mmol/L), creatinine (if value \>159 micromoles per liter \[µmol/L\]), direct bilirubin (if value \>1.35\*ULN), gamma glutamyl transferase (GGT) (if value \>3\*ULN), potassium (if value \>0.5 mmol/L below LLN and \>1.0 mmol/L above ULN), protein (if value \>15 g/L above ULN or below LLN), sodium (\>5 mmol/L below LLN or above ULN), urate (if value \>654 µmol/L) and urea (if value \>2\*ULN). Number of participants with chemistry parameters of PCC at 'any visit post-Baseline' are presented. |
| Number of Participants With Hematology Parameters of PCC | Up to Week 26 | Hematology parameters for which PCC values were identified were hematocrit (if value \>0.05 below LLN or \>0.04 above ULN), Hemoglobin (Hb) (if value \>20 g/L below LLN or \>10 g/L above ULN), lymphocytes (if value \<0.5\*LLN), neutrophils (if value \<1 giga unit per liter \[GI/L\]) and platelets (if value \<80 GI/L or \>500 GI/L). Number of participants with hematology parameters of PCC at 'any visit post-Baseline' are presented. |
| Number of Participants With Vital Signs of PCC | Up to Week 34 | Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a seated position after at least 5 minutes of rest. SBP values \<100 millimeters of mercury (mmHg) and \>170 mmHg, DBP values \<50 mmHg and \>110 mmHg, pulse rate values \<50 beats per minute (bpm) and \>120 bpm were considered as PCC values. Number of participants with PCC values of vital signs for 'any visit post-Baseline' are presented. |
| Number of Participants With Electrocardiogram (ECG) Parameters of PCC | Up to Week 26 | Single measurements of 12-lead ECG were obtained in semi recumbent position using an ECG machine that automatically calculates the heart rate and measures PR and QT interval corrected for heart rate according to Fridericia's formula (QTcF). Number of participants with ECG values of PCC at 'any visit post-Baseline' are presented. ECG mean heart rate values \<50 or \>120, PR interval \>300 milliseconds (msec), QRS interval \>200 msec, QTcF interval \>=500 msec were considered as PCC values. Number of participants with PCC values of ECG parameters for 'any visit post-Baseline' are presented. |
| Number of Participants With Positive Result for Anti-albiglutide Antibody | Up to Week 34 | Blood samples were obtained from participants at specific time points before administration of study treatment. The presence of anti-albiglutide antibodies was assessed using a validated enzyme linked immunosorbent assay (ELISA). The assay involves screening, confirmation, and titration steps (tiered-testing approach). Number of participants with positive anti- albiglutide antibody results at 'any visit post-Baseline' are presented. |
| Number of Participants With On-therapy Adverse Events (AEs) and Serious AEs (SAEs) | Up to Week 26 | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | Baseline and Week 26 | Blood samples were collected from participants at specific time points to evaluate FPG to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a MMRM model. |
| Change From Baseline in HbA1c Over Time | Baseline and up to Week 26 | Blood samples were collected from participants at specific time points to evaluate HbA1c to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a MMRM model and model-adjusted least square mean (LS mean) and standard error have been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). |
| Change From Baseline in FPG Over Time | Baseline and up to Week 26 | Blood samples were collected from participants at specific time points to evaluate FPG to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a MMRM model. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). |
| Trough Plasma Concentration of Albiglutide Over Time | Pre-dose at Week 12 and Week 26 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of albiglutide. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). |
| Number of Participants With Injection Site Reactions (ISR) | Up to Week 34 | Number of participants with ISR incidences were evaluated at specific time points. Each week included those participants with the onset of an ISR during that particular week as well as those participants with ISR from previous weeks that have not resolved. |
Countries
United States
Participant flow
Recruitment details
This repeat-dose study of albiglutide was conducted at 153 sites in the United States (US). A total of 624 participants with type 2 diabetes mellitus (T2DM) were screened; of these 316 were screen failures and 308 were randomized to receive albiglutide liquid drug product or lyophilized drug product in a 1:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| Albiglutide Liquid Eligible participants received 30 milligrams (mg) of albiglutide active liquid auto-injector along with placebo lyophilized dual chamber cartridge (DCC) pen injector once weekly for 4 weeks by subcutaneous (SC) injection in the abdomen, thigh, or upper arm. After 4 weeks, albiglutide dose was up-titrated to 50 mg for the remaining 22 weeks of the study treatment period. | 153 |
| Albiglutide Lyophilized Eligible participants received 30 mg of albiglutide active lyophilized DCC pen injector along with placebo liquid auto-injector once weekly for 4 weeks by SC injection in the abdomen, thigh, or upper arm. After 4 weeks, albiglutide dose was up-titrated to 50 mg for the remaining 22 weeks of the study treatment period. | 154 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lost to Follow-up | 5 | 6 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Albiglutide Liquid | Albiglutide Lyophilized | Total |
|---|---|---|---|
| Age, Continuous | 57.6 Years STANDARD_DEVIATION 9.25 | 56.6 Years STANDARD_DEVIATION 10.08 | 57.1 Years STANDARD_DEVIATION 9.67 |
| Race/Ethnicity, Customized Race/ethnicity customized American Indian (AI) or Alaska native Heritage | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Race/ethnicity customized Asian- Central/ South Asian Heritage | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/ethnicity customized Asian- Japanese/East Asian (EA)/South EA Heritage | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Race/ethnicity customized Black or African American (AA) Heritage | 15 Participants | 24 Participants | 39 Participants |
| Race/Ethnicity, Customized Race/ethnicity customized Multiple- AI or Alaska Native and White Heritage | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race/ethnicity customized Multiple- Black or AA and White Heritage | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race/ethnicity customized Native Hawaiian or Other Pacific Islander Heritage | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race/ethnicity customized White Heritage | 129 Participants | 122 Participants | 251 Participants |
| Sex: Female, Male Female | 70 Participants | 79 Participants | 149 Participants |
| Sex: Female, Male Male | 83 Participants | 75 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 153 | 0 / 154 |
| other Total, other adverse events | 101 / 153 | 94 / 154 |
| serious Total, serious adverse events | 7 / 153 | 9 / 154 |
Outcome results
Primary
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26
Blood samples will be collected from participants at specific time points to evaluate HbA1c to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a mixed-effect model with repeated measures (MMRM) method. The primary analysis will include all HbA1c values collected at scheduled visits from Week 4 up to Week 26. This will include values after hyperglycemia rescue and discontinuation from investigational product. Imputation under the non-inferiority null hypothesis for missing data will be incorporated.
Time frame: Baseline and Week 26
Population: Intent-To-Treat (ITT) Population comprised of all randomized participants who received at least one dose of study treatment and have a Baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide Liquid | Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26 | -1.12 Percentage of total hemoglobin | Standard Error 0.072 |
| Albiglutide Lyophilized | Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26 | -1.18 Percentage of total hemoglobin | Standard Error 0.072 |
p-value: 0.000295% CI: [-0.13, 0.24]MMRM model
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
Blood samples were collected from participants at specific time points to evaluate FPG to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a MMRM model.
Time frame: Baseline and Week 26
Population: ITT Population. Only those participants available at Week 26 were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide Liquid | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | -2.22 Mmol/L | Standard Error 0.191 |
| Albiglutide Lyophilized | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | -1.88 Mmol/L | Standard Error 0.195 |
95% CI: [-0.83, 0.14]
Secondary
Change From Baseline in FPG Over Time
Blood samples were collected from participants at specific time points to evaluate FPG to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a MMRM model. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time frame: Baseline and up to Week 26
Population: ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 26; n= 141, 136 | -2.22 Mmol/L | Standard Error 0.191 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 1; n= 148, 144 | -1.04 Mmol/L | Standard Error 0.165 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 2; n= 143, 145 | -1.52 Mmol/L | Standard Error 0.18 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 3; n= 145, 140 | -1.71 Mmol/L | Standard Error 0.168 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 4; n= 142, 145 | -1.93 Mmol/L | Standard Error 0.162 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 5; n= 146, 143 | -2.04 Mmol/L | Standard Error 0.16 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 6; n= 145, 145 | -2.07 Mmol/L | Standard Error 0.167 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 7; n= 146, 144 | -1.93 Mmol/L | Standard Error 0.176 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 8; n= 143, 141 | -2.19 Mmol/L | Standard Error 0.169 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 9; n= 142, 141 | -2.05 Mmol/L | Standard Error 0.178 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 10; n= 141, 142 | -2.03 Mmol/L | Standard Error 0.173 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 11; n= 141, 139 | -2.01 Mmol/L | Standard Error 0.181 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 12; n= 137, 137 | -2.16 Mmol/L | Standard Error 0.176 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 13; n= 140, 136 | -2.04 Mmol/L | Standard Error 0.202 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 16; n= 140, 140 | -2.02 Mmol/L | Standard Error 0.189 |
| Albiglutide Liquid | Change From Baseline in FPG Over Time | Week 20; n= 139, 134 | -1.87 Mmol/L | Standard Error 0.197 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 12; n= 137, 137 | -2.19 Mmol/L | Standard Error 0.178 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 26; n= 141, 136 | -1.88 Mmol/L | Standard Error 0.195 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 8; n= 143, 141 | -2.38 Mmol/L | Standard Error 0.171 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 1; n= 148, 144 | -1.29 Mmol/L | Standard Error 0.167 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 9; n= 142, 141 | -2.08 Mmol/L | Standard Error 0.18 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 2; n= 143, 145 | -1.77 Mmol/L | Standard Error 0.181 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 13; n= 140, 136 | -2.09 Mmol/L | Standard Error 0.205 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 3; n= 145, 140 | -1.70 Mmol/L | Standard Error 0.17 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 10; n= 141, 142 | -2.17 Mmol/L | Standard Error 0.175 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 4; n= 142, 145 | -1.91 Mmol/L | Standard Error 0.164 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 20; n= 139, 134 | -1.90 Mmol/L | Standard Error 0.201 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 5; n= 146, 143 | -2.23 Mmol/L | Standard Error 0.162 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 11; n= 141, 139 | -2.12 Mmol/L | Standard Error 0.184 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 6; n= 145, 145 | -2.22 Mmol/L | Standard Error 0.169 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 16; n= 140, 140 | -2.09 Mmol/L | Standard Error 0.191 |
| Albiglutide Lyophilized | Change From Baseline in FPG Over Time | Week 7; n= 146, 144 | -2.20 Mmol/L | Standard Error 0.179 |
95% CI: [-0.15, 0.65]
95% CI: [-0.2, 0.69]
95% CI: [-0.42, 0.4]
95% CI: [-0.42, 0.36]
95% CI: [-0.19, 0.57]
95% CI: [-0.26, 0.55]
95% CI: [-0.16, 0.71]
95% CI: [-0.22, 0.6]
95% CI: [-0.41, 0.47]
95% CI: [-0.28, 0.57]
95% CI: [-0.34, 0.56]
95% CI: [-0.41, 0.46]
95% CI: [-0.47, 0.57]
95% CI: [-0.41, 0.54]
95% CI: [-0.47, 0.53]
95% CI: [-0.83, 0.14]
Secondary
Change From Baseline in HbA1c Over Time
Blood samples were collected from participants at specific time points to evaluate HbA1c to monitor for potential hyperglycemia. The last measurement collected prior to the first dose of randomized study treatment was considered as Baseline value. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The analysis was performed using a MMRM model and model-adjusted least square mean (LS mean) and standard error have been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time frame: Baseline and up to Week 26
Population: ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide Liquid | Change From Baseline in HbA1c Over Time | Week 8; 145, 147 | -0.96 Percent of total hemoglobin | Standard Error 0.057 |
| Albiglutide Liquid | Change From Baseline in HbA1c Over Time | Week 16; n= 136, 144 | -1.25 Percent of total hemoglobin | Standard Error 0.07 |
| Albiglutide Liquid | Change From Baseline in HbA1c Over Time | Week 4; n= 148, 149 | -0.50 Percent of total hemoglobin | Standard Error 0.045 |
| Albiglutide Liquid | Change From Baseline in HbA1c Over Time | Week 12; n= 137, 145 | -1.15 Percent of total hemoglobin | Standard Error 0.065 |
| Albiglutide Liquid | Change From Baseline in HbA1c Over Time | Week 26; n= 138, 141 | -1.16 Percent of total hemoglobin | Standard Error 0.071 |
| Albiglutide Liquid | Change From Baseline in HbA1c Over Time | Week 20; n= 137, 142 | -1.24 Percent of total hemoglobin | Standard Error 0.067 |
| Albiglutide Lyophilized | Change From Baseline in HbA1c Over Time | Week 26; n= 138, 141 | -1.17 Percent of total hemoglobin | Standard Error 0.071 |
| Albiglutide Lyophilized | Change From Baseline in HbA1c Over Time | Week 4; n= 148, 149 | -0.54 Percent of total hemoglobin | Standard Error 0.046 |
| Albiglutide Lyophilized | Change From Baseline in HbA1c Over Time | Week 8; 145, 147 | -1.02 Percent of total hemoglobin | Standard Error 0.057 |
| Albiglutide Lyophilized | Change From Baseline in HbA1c Over Time | Week 12; n= 137, 145 | -1.23 Percent of total hemoglobin | Standard Error 0.064 |
| Albiglutide Lyophilized | Change From Baseline in HbA1c Over Time | Week 16; n= 136, 144 | -1.27 Percent of total hemoglobin | Standard Error 0.07 |
| Albiglutide Lyophilized | Change From Baseline in HbA1c Over Time | Week 20; n= 137, 142 | -1.26 Percent of total hemoglobin | Standard Error 0.066 |
p-value: <0.000195% CI: [-0.07, 0.13]MMRM model
p-value: <0.000195% CI: [-0.07, 0.2]MMRM model
p-value: <0.000195% CI: [-0.08, 0.24]MMRM model
p-value: <0.000195% CI: [-0.16, 0.2]MMRM model
p-value: <0.000195% CI: [-0.15, 0.19]MMRM model
p-value: <0.000195% CI: [-0.17, 0.2]MMRM model
Secondary
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC)
Chemistry parameters for which PCC values were identified were alanine aminotransferase (ALT) (if value \>3 \* upper limit of normal \[ULN\]), albumin (if value \>5 gram/liter \[g/L\] above ULN or below lower limit of normal \[LLN\]), alkaline phosphatase (alk.phosph.) (if value \>3\*ULN), aspartate aminotransferase (AST) (if value \>3\*ULN), total bilirubin (if value \>1.5 ULN), calcium (if value \<1.8 or \>3.0 millimoles per liter \[mmol/L\]), carbon di oxide (CO2) (if value \<16 or \>40 mmol/L), creatinine (if value \>159 micromoles per liter \[µmol/L\]), direct bilirubin (if value \>1.35\*ULN), gamma glutamyl transferase (GGT) (if value \>3\*ULN), potassium (if value \>0.5 mmol/L below LLN and \>1.0 mmol/L above ULN), protein (if value \>15 g/L above ULN or below LLN), sodium (\>5 mmol/L below LLN or above ULN), urate (if value \>654 µmol/L) and urea (if value \>2\*ULN). Number of participants with chemistry parameters of PCC at 'any visit post-Baseline' are presented.
Time frame: Up to Week 26
Population: Safety Population. Only those participants present at 'any visit post-Baseline' are analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Potassium; >0.5 mmol/L below LLN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | ALT; >3*ULN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Albumin; >5 g/L below LLN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Albumin; >5 g/L above ULN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Alk.phosph.; >3*ULN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | AST; >3*ULN | 1 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Bilirubin; >1.5*ULN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Calcium; <1.8 mmol/L | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Calcium; >3.0 mmol/L | 1 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | CO2; <16 mmol/L | 1 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | CO2; >40 mmol/L | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Creatinine; >159 µmol/L | 1 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Direct bilirubin; >1.35ULN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | GGT; >3*ULN | 1 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Potassium; >1.0 mmol/L above ULN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Protein; >15 g/L below LLN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Protein; >15 g/L above ULN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Sodium; >5 mmol/L below LLN | 1 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Sodium; >5 mmol/L above ULN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Urate; >654 µmol/L | 1 Participants |
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Urea; >2*ULN | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | CO2; >40 mmol/L | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Sodium; >5 mmol/L above ULN | 2 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Protein; >15 g/L below LLN | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | ALT; >3*ULN | 1 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Creatinine; >159 µmol/L | 1 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Albumin; >5 g/L below LLN | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Urate; >654 µmol/L | 1 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Albumin; >5 g/L above ULN | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Direct bilirubin; >1.35ULN | 1 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Alk.phosph.; >3*ULN | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Protein; >15 g/L above ULN | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | AST; >3*ULN | 1 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | GGT; >3*ULN | 4 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Bilirubin; >1.5*ULN | 2 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Potassium; >0.5 mmol/L below LLN | 1 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Calcium; <1.8 mmol/L | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Urea; >2*ULN | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Calcium; >3.0 mmol/L | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Potassium; >1.0 mmol/L above ULN | 1 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | CO2; <16 mmol/L | 6 Participants |
| Albiglutide Lyophilized | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern (PCC) | Sodium; >5 mmol/L below LLN | 0 Participants |
Secondary
Number of Participants With Electrocardiogram (ECG) Parameters of PCC
Single measurements of 12-lead ECG were obtained in semi recumbent position using an ECG machine that automatically calculates the heart rate and measures PR and QT interval corrected for heart rate according to Fridericia's formula (QTcF). Number of participants with ECG values of PCC at 'any visit post-Baseline' are presented. ECG mean heart rate values \<50 or \>120, PR interval \>300 milliseconds (msec), QRS interval \>200 msec, QTcF interval \>=500 msec were considered as PCC values. Number of participants with PCC values of ECG parameters for 'any visit post-Baseline' are presented.
Time frame: Up to Week 26
Population: Safety Population. Only those participants present at 'any visit post-Baseline' are analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Liquid | Number of Participants With Electrocardiogram (ECG) Parameters of PCC | QTcF interval; >=500 msec | 0 Participants |
| Albiglutide Liquid | Number of Participants With Electrocardiogram (ECG) Parameters of PCC | ECG mean heart rate; <50 bpm | 2 Participants |
| Albiglutide Liquid | Number of Participants With Electrocardiogram (ECG) Parameters of PCC | ECG mean heart rate; >120 bpm | 1 Participants |
| Albiglutide Liquid | Number of Participants With Electrocardiogram (ECG) Parameters of PCC | PR interval; >300 msec | 1 Participants |
| Albiglutide Liquid | Number of Participants With Electrocardiogram (ECG) Parameters of PCC | QRS duration; >200 msec | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Electrocardiogram (ECG) Parameters of PCC | QRS duration; >200 msec | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Electrocardiogram (ECG) Parameters of PCC | PR interval; >300 msec | 2 Participants |
| Albiglutide Lyophilized | Number of Participants With Electrocardiogram (ECG) Parameters of PCC | ECG mean heart rate; <50 bpm | 2 Participants |
| Albiglutide Lyophilized | Number of Participants With Electrocardiogram (ECG) Parameters of PCC | QTcF interval; >=500 msec | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Electrocardiogram (ECG) Parameters of PCC | ECG mean heart rate; >120 bpm | 0 Participants |
Secondary
Number of Participants With Hematology Parameters of PCC
Hematology parameters for which PCC values were identified were hematocrit (if value \>0.05 below LLN or \>0.04 above ULN), Hemoglobin (Hb) (if value \>20 g/L below LLN or \>10 g/L above ULN), lymphocytes (if value \<0.5\*LLN), neutrophils (if value \<1 giga unit per liter \[GI/L\]) and platelets (if value \<80 GI/L or \>500 GI/L). Number of participants with hematology parameters of PCC at 'any visit post-Baseline' are presented.
Time frame: Up to Week 26
Population: Safety Population. Only those participants present at 'any visit post-Baseline' are analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Liquid | Number of Participants With Hematology Parameters of PCC | Hematocrit; >0.05 (fraction of 1) below LLN | 2 Participants |
| Albiglutide Liquid | Number of Participants With Hematology Parameters of PCC | Hematocrit; >0.04 (fraction of 1) above ULN | 5 Participants |
| Albiglutide Liquid | Number of Participants With Hematology Parameters of PCC | Hb; >20 g/L below LLN | 3 Participants |
| Albiglutide Liquid | Number of Participants With Hematology Parameters of PCC | Hb; >10 g/L above ULN | 2 Participants |
| Albiglutide Liquid | Number of Participants With Hematology Parameters of PCC | Lymphocytes; <0.5*LLN | 0 Participants |
| Albiglutide Liquid | Number of Participants With Hematology Parameters of PCC | Neutrophils; <1 GI/L | 1 Participants |
| Albiglutide Liquid | Number of Participants With Hematology Parameters of PCC | Platelets; <80 GI/L | 0 Participants |
| Albiglutide Liquid | Number of Participants With Hematology Parameters of PCC | Platelets; >500 GI/L | 1 Participants |
| Albiglutide Lyophilized | Number of Participants With Hematology Parameters of PCC | Platelets; >500 GI/L | 1 Participants |
| Albiglutide Lyophilized | Number of Participants With Hematology Parameters of PCC | Hematocrit; >0.05 (fraction of 1) below LLN | 6 Participants |
| Albiglutide Lyophilized | Number of Participants With Hematology Parameters of PCC | Lymphocytes; <0.5*LLN | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Hematology Parameters of PCC | Hematocrit; >0.04 (fraction of 1) above ULN | 2 Participants |
| Albiglutide Lyophilized | Number of Participants With Hematology Parameters of PCC | Platelets; <80 GI/L | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Hematology Parameters of PCC | Hb; >20 g/L below LLN | 9 Participants |
| Albiglutide Lyophilized | Number of Participants With Hematology Parameters of PCC | Neutrophils; <1 GI/L | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Hematology Parameters of PCC | Hb; >10 g/L above ULN | 2 Participants |
Secondary
Number of Participants With Injection Site Reactions (ISR)
Number of participants with ISR incidences were evaluated at specific time points. Each week included those participants with the onset of an ISR during that particular week as well as those participants with ISR from previous weeks that have not resolved.
Time frame: Up to Week 34
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide Liquid | Number of Participants With Injection Site Reactions (ISR) | 17 Participants |
| Albiglutide Lyophilized | Number of Participants With Injection Site Reactions (ISR) | 18 Participants |
Secondary
Number of Participants With On-therapy Adverse Events (AEs) and Serious AEs (SAEs)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function.
Time frame: Up to Week 26
Population: Safety Population comprised of all enrolled participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Liquid | Number of Participants With On-therapy Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 101 Participnats |
| Albiglutide Liquid | Number of Participants With On-therapy Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 7 Participnats |
| Albiglutide Lyophilized | Number of Participants With On-therapy Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 94 Participnats |
| Albiglutide Lyophilized | Number of Participants With On-therapy Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 9 Participnats |
Secondary
Number of Participants With Positive Result for Anti-albiglutide Antibody
Blood samples were obtained from participants at specific time points before administration of study treatment. The presence of anti-albiglutide antibodies was assessed using a validated enzyme linked immunosorbent assay (ELISA). The assay involves screening, confirmation, and titration steps (tiered-testing approach). Number of participants with positive anti- albiglutide antibody results at 'any visit post-Baseline' are presented.
Time frame: Up to Week 34
Population: Safety Population. Only those participants present at 'any visit post-Baseline' are analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide Liquid | Number of Participants With Positive Result for Anti-albiglutide Antibody | 17 Participants |
| Albiglutide Lyophilized | Number of Participants With Positive Result for Anti-albiglutide Antibody | 16 Participants |
Secondary
Number of Participants With Vital Signs of PCC
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a seated position after at least 5 minutes of rest. SBP values \<100 millimeters of mercury (mmHg) and \>170 mmHg, DBP values \<50 mmHg and \>110 mmHg, pulse rate values \<50 beats per minute (bpm) and \>120 bpm were considered as PCC values. Number of participants with PCC values of vital signs for 'any visit post-Baseline' are presented.
Time frame: Up to Week 34
Population: Safety Population. Only those participants present at 'any visit post-Baseline' are analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Liquid | Number of Participants With Vital Signs of PCC | Pulse rate; > 120 bpm | 1 Participants |
| Albiglutide Liquid | Number of Participants With Vital Signs of PCC | SBP: <100 mmHg | 18 Participants |
| Albiglutide Liquid | Number of Participants With Vital Signs of PCC | SBP; >170 mmHg | 11 Participants |
| Albiglutide Liquid | Number of Participants With Vital Signs of PCC | DBP; <50 mmHg | 0 Participants |
| Albiglutide Liquid | Number of Participants With Vital Signs of PCC | DBP; > 110 mmHg | 3 Participants |
| Albiglutide Liquid | Number of Participants With Vital Signs of PCC | Pulse rate; < 50 bpm | 5 Participants |
| Albiglutide Lyophilized | Number of Participants With Vital Signs of PCC | DBP; > 110 mmHg | 3 Participants |
| Albiglutide Lyophilized | Number of Participants With Vital Signs of PCC | Pulse rate; > 120 bpm | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Vital Signs of PCC | DBP; <50 mmHg | 0 Participants |
| Albiglutide Lyophilized | Number of Participants With Vital Signs of PCC | SBP: <100 mmHg | 16 Participants |
| Albiglutide Lyophilized | Number of Participants With Vital Signs of PCC | Pulse rate; < 50 bpm | 2 Participants |
| Albiglutide Lyophilized | Number of Participants With Vital Signs of PCC | SBP; >170 mmHg | 13 Participants |
Secondary
Trough Plasma Concentration of Albiglutide Over Time
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of albiglutide. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time frame: Pre-dose at Week 12 and Week 26
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide Liquid | Trough Plasma Concentration of Albiglutide Over Time | Week 12; n= 127, 130 | 3996.9 Nanograms per milliliter (ng/mL) | Standard Deviation 1613.02 |
| Albiglutide Liquid | Trough Plasma Concentration of Albiglutide Over Time | Week 26; n= 127, 127 | 4196.6 Nanograms per milliliter (ng/mL) | Standard Deviation 1500.57 |
| Albiglutide Lyophilized | Trough Plasma Concentration of Albiglutide Over Time | Week 12; n= 127, 130 | 3927.1 Nanograms per milliliter (ng/mL) | Standard Deviation 1537.45 |
| Albiglutide Lyophilized | Trough Plasma Concentration of Albiglutide Over Time | Week 26; n= 127, 127 | 3929.1 Nanograms per milliliter (ng/mL) | Standard Deviation 1338.08 |