Diabetes Mellitus, Type 2
Conditions
Keywords
pharmacokinetics, pharmacodynamics, GSK716155, albiglutide
Brief summary
The first part of the study includes a single dose treatment period to evaluate the pharmacokinetic bioequivalence of a subcutaneous injection of albiglutide from process 2 drug substance compared with process 3 drug substance. The second part of the treatment period will evaluate additional pharmacokinetic and pharmacodynamic parameters and safety and tolerability of repeat doses of albiglutide given weekly for 12 weeks from process 2 drug substance compared with process 3 drug substance. Subjects with type 2 diabetes whose glycemia is inadequately controlled on their current regimen of diet and exercise or stable dose of metformin will be recruited into the study.
Detailed description
This is a randomized, double-blind, multicenter, 2 parallel group study. The first part of the treatment period will evaluate the pharmacokinetic bioequivalence of a single dose of a subcutaneous injection of 30mg of albiglutide from process 2 drug substance compared with process 3 drug substance. The second part of the treatment period will evaluate additional pharmacokinetic parameters, pharmacodynamic parameters, immunogenicity, effects on glycosylated hemoglobin and fasting plasma glucose, and safety and tolerability of repeat doses of subcutaneous injections of 30mg of albiglutide given weekly for 12 weeks from process 2 drug substance compared with process 3 drug substance. Subjects with type 2 diabetes whose glycemia is inadequately controlled on their current regimen of diet and exercise or stable dose of metformin will be recruited into the study.
Interventions
BIOLOGICALalbiglutide (GSK716155)
subcutaneous injection administered once a week
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
* Subjects with a historical diagnosis of type 2 diabetes mellitus who are experiencing inadequate glycemic control on their current regimen of diet and exercise or on a stable dose of metformin * Body mass index ≥20 kg/m2 and ≤45 kg/m2 * Fasting C-peptide ≥0.8 ng/mL (≥0.26 nmol/L) * Thyroid-stimulating hormone level is normal or clinically euthyroid * Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception.
Exclusion criteria
* Current ongoing symptomatic biliary disease or history of pancreatitis * History of significant GI surgery * Recent clinically significant cardiovascular and/or cerebrovascular disease * History of human immunodeficiency virus infection * History of, or current hepatic disease * History of alcohol or substance abuse * Female subject is pregnant, lactating, or \<6 weeks postpartum * History of type 1 diabetes * Receipt of any investigational drug within the 30 days, or 5 half-lives whichever is longer, before Screening or a history of receipt of an investigational antidiabetic drug within the 3 months before randomization, or receipt of any GLP-1 agents including albiglutide * History of, or family history of thyroid disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-inf) of Albiglutide in the Bioequivalence (BE) Phase | Pre-dose at Baseline; 24 hours (hr), 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose | To assess the bioequivalence of the two formulations of albiglutide, an analysis of variance (ANOVA) model with treatment as a fixed effect was applied to the natural-log-transformed parameter AUC(0-inf) estimated from the BE Phase. AUC is a measure of how much albiglutide is in the blood at certain time points. The Process 2 treatment group (albiglutide derived from process 2) was the reference group and was compared with the Process 3 treatment group (albiglutide derived from process 3) as the test group (i.e., treatment comparisons based on the ratio of Process 3:Process 2). Blood samples for pharmacokinetic analysis were collected prior to dosing at Baseline and 24 hours (hr), 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication. |
| Maximum Observed Plasma Concentration (Cmax) of Albiglutide in the BE Phase | Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose | To assess the bioequivalence of the two formulations of study drug, an analysis of variance (ANOVA) model with treatment as a fixed effect was applied to the natural-log-transformed parameter Cmax estimated from the BE phase. The Process 2 treatment group (albiglutide derived from process 2) was the reference group and was compared with the Process 3 treatment group (albiglutide derived from process 3) as the test group (i.e., treatment comparisons based on the ratio of Process 3:Process 2). Blood samples for pharmacokinetic analysis were collected prior to dosing at Baseline and 24 hours (hr), 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC (0-last) and AUC (0-inf) of Albiglutide in the BE Phase | Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose | The area under the concentration-time (AUC) curve from time zero to the last quantifiable concentration (0-last) and AUC (0-inf) of albiglutide in the BE Phase were measured. AUC is a measure of how much albiglutide is in the blood at certain time points. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication. |
| Tmax and Tlag of Albiglutide in the BE Phase | Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose | Time of the maximum observed plasma concentration (tmax) and the observed time prior to the first quantifiable plasma concentration (tlag) of albiglutide in the BE Phase were measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication. |
| Cmax of Albiglutide in the BE Phase | Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose | Cmax of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication. |
| t1/2 of Albiglutide in the BE Phase | Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose | The terminal elimination half-life (t1/2) of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication. |
| Apparent Clearance of Albiglutide in the BE Phase | Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose | The apparent clearance (CL/F) of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication. |
| Apparent Volume of Distribution in the Terminal Phase of Albiglutide in BE Phase | Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose | The apparent volume of distribution in the terminal phase (V/F) of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication. |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 17 | Baseline and Week 17 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. This analysis used the last observation carried forward (LOCF) method for missing post-Baseline HbA1c values. HbA1c values obtained after hyperglycemic rescue were treated as missing and replaced with pre-rescue values. Baseline is defined as the last available assessment on or prior to the day on which the first dose of study drug was received. Based on analysis of covariance (ANCOVA): Change = treatment + Baseline HbA1c + age category + weight category + background antidiabetic therapy category. |
| Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Immediately pre-dose at Week 5, Week 9, Week 13, Week 17 (End of Treatment [EOT]), and Week 25 (Follow-up) | The trough concentration of albiglutide at Week 5, Week 9, Week 13, Week 17 (EOT), and Week 25 (Follow-up) following multiple-dose administration was estimated. The time and date of sample collection pre-dose was to be recorded. |
| Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | From the time the participant consented to participate in the study through Visit 28 (Week 25) or the final follow-up visit, for participants who discontinued active participation in the study | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. Hypoglycemic events are excluded from this table, except for serious adverse events. |
| Number of Participants With Indicated Adverse Events of Special Interest | From the time the participant consented to participate in the study through Visit 28 (Week 25) or the final follow-up visit, for participants who discontinue active participation in the study | Adverse events of special interest included cardiovascular events, hypoglycemic events, pancreatitis events, thyroid events, gastrointestinal (GI) events, diabetic retinopathy events, systemic allergic reactions (SAR), injection site reactions (ISR), and liver events (AEs from investigations and hepatobiliary disorders were considered). |
| Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit | Week 1 through Week 25 | Criteria for values of potential concern were determined by the medical monitors. For hematocrit, a \>0.1 decrease from Baseline was considered to be of clinical concern. For hemoglobin, a \>25 grams per liter (g/L) decrease from Baseline was considered to be of clinical concern. |
| Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | Week 1 through Week 25 | Vital signs measured included systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate. Criteria for values of potential concern were determined by the medical monitors. For SBP, a decrease or increase \>30 millimeters of mercury (mmHg) from Baseline was considered to be of clinical concern. For DBP, a decrease or increase \>20 mmHg from Baseline was considered to be of clinical concern. For heart rate, a decrease or increase \>30 beats per minute (bpm) was considered to be of clinical concern. |
| Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Screening and Week 17 | A complete physical examination was performed at Screening and at Week 17 and included evaluation of the following organ or body systems: skin (including injection site); head; eyes; ears, sose, and throat (ENT); thyroid; respiratory system; cardiovascular system; abdomen (liver, spleen); lymph nodes; central nervous system (CNT); and extremities. The assessment was categorized as improved, no change, worsened, and not done. |
| Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit | Week 1 through Week 25 | ECG parameters include heart rate, QRS interval, QTinterval, QT interval - Bazett correction (QTcB), QT interval - Fridericia correction (QTcF), RR interval, and PR interval. Criteria for values of potential concern were determined by the medical monitors. For the QRS interval, an increase of \>25% when Baseline QRS \>100 milliseconds (msec) and an increase of \>50% when Baseline QRS \<=100 msec was considered to be of clinical concern. For QTcF, a \>=60 msec change from Baseline was considered to be of clinical concern. For the PR interval, an increase of \>25% when Baseline PR \>200 msec and an increase of \>50% when Baseline PR \<=200 msec was considered to be of clinical concern. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 17 | Baseline and Week 17 | This analysis used the LOCF method for missing post-Baseline FPG values. FPG values obtained after hyperglycemic rescue were treated as missing and replaced with pre-rescue values. Baseline is defined as the last available assessment on or prior to the day on which the first dose of study drug was received. Based on ANCOVA: Change = treatment + Baseline FPG + age category + weight category + background antidiabetic therapy category. |
| Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Baseline, Week 5, Week 9, Week 13, Week 17, and Week 25 (Follow-up) | The presence of anti-albiglutide antibodies after repeat-dose administration was assessed using a qualified enzyme-linked immunosorbent assay. The assay involved screening, confirmation, and titration steps (tiered-testing approach). The number of participants who tested positive for anti-albiglutide antibodies are presented by visit. |
Countries
United States
Participant flow
Recruitment details
The enrollment number reflects the 283 participants starting the Multiple-dose Phase.
Pre-assignment details
This study was comprised of a Screening Period (up to 2 weeks), a Run-in Period (4 weeks), a Treatment Period (TP: 17 weeks), and a Follow-up (8 weeks) Period. The TP had a Single-dose Phase (Bioequivalence \[BE\] Phase: 28 days) and a 12-week Multiple-dose Phase. In the BE Phase, 186 participants were randomized; 167 received \>=1 treatment dose.
Participants by arm
| Arm | Count |
|---|---|
| Albiglutide Process 2 During the BE Phase, participants received a single dose of albiglutide 30 mg from the Process 2 drug product, injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen. After completing the BE phase, participants progressed into the Multiple-dose Phase of the study, beginning at Week 5, during which participants received 12 weekly injections of albiglutide 30 mg from the Process 2 drug product, injected subcutaneously into the abdomen, alternating between the right and left sides of the body, using a fixed-dose, prefilled, single-use injector pen. Additional participants (other than those completing the BE Phase and progressing to the Multiple-dose Phase) were randomized into the Multiple-dose Phase of the study. All participants returned for the 8-week post-treatment follow-up visit. | 141 |
| Albiglutide Process 3 During the BE Phase, participants received a single dose of albiglutide 30 mg from the Process 3 drug product, injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen. After completing the BE phase, participants progressed into the Multiple-dose Phase of the study, beginning at Week 5, during which participants received 12 weekly injections of albiglutide 30 mg from the Process 3 drug product, injected subcutaneously into the abdomen, alternating between the right and left sides of the body, using a fixed-dose, prefilled, single-use injector pen. Additional participants (other than those completing the BE Phase and progressing to the Multiple-dose Phase) were randomized into the Multiple-dose Phase of the study. All participants returned for the 8-week post-treatment follow-up visit. | 142 |
| Total | 283 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Phase (FUP) (8 Weeks) | Hyperglycemia | 1 | 0 |
| Follow-up Phase (FUP) (8 Weeks) | Lost to Follow-up | 0 | 4 |
| Follow-up Phase (FUP) (8 Weeks) | Noncompliance | 1 | 0 |
| Follow-up Phase (FUP) (8 Weeks) | Withdrawal by Subject | 1 | 0 |
| Multiple-dose Phase (MDP) (Overall) | Adverse Event | 2 | 2 |
| Multiple-dose Phase (MDP) (Overall) | Lost to Follow-up | 0 | 2 |
| Multiple-dose Phase (MDP) (Overall) | Noncompliance | 0 | 2 |
| Multiple-dose Phase (MDP) (Overall) | Physician Decision | 2 | 1 |
| Multiple-dose Phase (MDP) (Overall) | Withdrawal by Subject | 5 | 2 |
| Multiple-dose Phase (MDP) (Overall) | Withdrawn Due to Hyperglycemia | 7 | 7 |
| Single-dose Phase (BE Phase: 28 Days) | Persistent Hyperglycemia | 1 | 1 |
| Single-dose Phase (BE Phase: 28 Days) | Physician Decision | 1 | 0 |
| Single-dose Phase (BE Phase: 28 Days) | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Albiglutide Process 2 | Albiglutide Process 3 | Total |
|---|---|---|---|
| Age, Continuous | 52.6 Years STANDARD_DEVIATION 11.18 | 54.4 Years STANDARD_DEVIATION 10.53 | 53.5 Years STANDARD_DEVIATION 10.88 |
| Gender Female | 78 Participants | 76 Participants | 154 Participants |
| Gender Male | 63 Participants | 66 Participants | 129 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 15 Participants | 20 Participants | 35 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 120 Participants | 117 Participants | 237 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 84 / 141 | 69 / 142 |
| serious Total, serious adverse events | 5 / 141 | 1 / 142 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-inf) of Albiglutide in the Bioequivalence (BE) Phase
To assess the bioequivalence of the two formulations of albiglutide, an analysis of variance (ANOVA) model with treatment as a fixed effect was applied to the natural-log-transformed parameter AUC(0-inf) estimated from the BE Phase. AUC is a measure of how much albiglutide is in the blood at certain time points. The Process 2 treatment group (albiglutide derived from process 2) was the reference group and was compared with the Process 3 treatment group (albiglutide derived from process 3) as the test group (i.e., treatment comparisons based on the ratio of Process 3:Process 2). Blood samples for pharmacokinetic analysis were collected prior to dosing at Baseline and 24 hours (hr), 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.
Time frame: Pre-dose at Baseline; 24 hours (hr), 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
Population: Albiglutide Pharmacokinetic (PK) Population: all participants who had sufficient samples to calculate PK parameters of albiglutide. Participants with insufficient concentration data or an unestimable terminal elimination rate constant were excluded from analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide Process 2 | Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-inf) of Albiglutide in the Bioequivalence (BE) Phase | 496190.200 nanograms*hour/milliliter | Geometric Coefficient of Variation 42 |
| Albiglutide Process 3 | Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-inf) of Albiglutide in the Bioequivalence (BE) Phase | 464985.355 nanograms*hour/milliliter | Geometric Coefficient of Variation 40 |
90% CI: [0.842, 1.042]ANOVA
Primary
Maximum Observed Plasma Concentration (Cmax) of Albiglutide in the BE Phase
To assess the bioequivalence of the two formulations of study drug, an analysis of variance (ANOVA) model with treatment as a fixed effect was applied to the natural-log-transformed parameter Cmax estimated from the BE phase. The Process 2 treatment group (albiglutide derived from process 2) was the reference group and was compared with the Process 3 treatment group (albiglutide derived from process 3) as the test group (i.e., treatment comparisons based on the ratio of Process 3:Process 2). Blood samples for pharmacokinetic analysis were collected prior to dosing at Baseline and 24 hours (hr), 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.
Time frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
Population: Albiglutide PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide Process 2 | Maximum Observed Plasma Concentration (Cmax) of Albiglutide in the BE Phase | 1881.053 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 58 |
| Albiglutide Process 3 | Maximum Observed Plasma Concentration (Cmax) of Albiglutide in the BE Phase | 1743.053 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49 |
90% CI: [0.813, 1.056]ANOVA
Secondary
Apparent Clearance of Albiglutide in the BE Phase
The apparent clearance (CL/F) of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.
Time frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
Population: Albiglutide PK Population. Participants with insufficient concentration data or an unestimable terminal elimination rate constant were excluded from analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide Process 2 | Apparent Clearance of Albiglutide in the BE Phase | 0.06046 Liters per hour | Geometric Coefficient of Variation 41.8 |
| Albiglutide Process 3 | Apparent Clearance of Albiglutide in the BE Phase | 0.06452 Liters per hour | Geometric Coefficient of Variation 39.7 |
Secondary
Apparent Volume of Distribution in the Terminal Phase of Albiglutide in BE Phase
The apparent volume of distribution in the terminal phase (V/F) of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.
Time frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
Population: Albiglutide PK Population. Participants with insufficient concentration data or an unestimable terminal elimination rate constant were excluded from analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide Process 2 | Apparent Volume of Distribution in the Terminal Phase of Albiglutide in BE Phase | 9.283 Liters | Geometric Coefficient of Variation 44 |
| Albiglutide Process 3 | Apparent Volume of Distribution in the Terminal Phase of Albiglutide in BE Phase | 10.595 Liters | Geometric Coefficient of Variation 44.3 |
Secondary
AUC (0-last) and AUC (0-inf) of Albiglutide in the BE Phase
The area under the concentration-time (AUC) curve from time zero to the last quantifiable concentration (0-last) and AUC (0-inf) of albiglutide in the BE Phase were measured. AUC is a measure of how much albiglutide is in the blood at certain time points. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.
Time frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
Population: Albiglutide PK Population. Participants with insufficient concentration data or an unestimable terminal elimination rate constant were excluded from analysis. Different par. may have been analyzed at different time points; the overall number of par. analyzed reflects everyone in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide Process 2 | AUC (0-last) and AUC (0-inf) of Albiglutide in the BE Phase | AUC (0-inf), n=75, 74 | 496190.2 nanograms*hour/milliliter | Geometric Coefficient of Variation 41.8 |
| Albiglutide Process 2 | AUC (0-last) and AUC (0-inf) of Albiglutide in the BE Phase | AUC (0-last), n=84, 80 | 447294.0 nanograms*hour/milliliter | Geometric Coefficient of Variation 55.5 |
| Albiglutide Process 3 | AUC (0-last) and AUC (0-inf) of Albiglutide in the BE Phase | AUC (0-last), n=84, 80 | 426263.5 nanograms*hour/milliliter | Geometric Coefficient of Variation 45.2 |
| Albiglutide Process 3 | AUC (0-last) and AUC (0-inf) of Albiglutide in the BE Phase | AUC (0-inf), n=75, 74 | 464985.4 nanograms*hour/milliliter | Geometric Coefficient of Variation 39.7 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 17
This analysis used the LOCF method for missing post-Baseline FPG values. FPG values obtained after hyperglycemic rescue were treated as missing and replaced with pre-rescue values. Baseline is defined as the last available assessment on or prior to the day on which the first dose of study drug was received. Based on ANCOVA: Change = treatment + Baseline FPG + age category + weight category + background antidiabetic therapy category.
Time frame: Baseline and Week 17
Population: Efficacy Population - LOCF
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide Process 2 | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 17 | -1.11 millimoles per liter | Standard Error 0.231 |
| Albiglutide Process 3 | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 17 | -1.21 millimoles per liter | Standard Error 0.231 |
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 17
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. This analysis used the last observation carried forward (LOCF) method for missing post-Baseline HbA1c values. HbA1c values obtained after hyperglycemic rescue were treated as missing and replaced with pre-rescue values. Baseline is defined as the last available assessment on or prior to the day on which the first dose of study drug was received. Based on analysis of covariance (ANCOVA): Change = treatment + Baseline HbA1c + age category + weight category + background antidiabetic therapy category.
Time frame: Baseline and Week 17
Population: Efficacy Population - LOCF: all participants who received a dose of study medication and who had a Baseline measurement and at least 1 post-Baseline HbA1c or fasting plasma glucose (FPG) measurement. Only participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide Process 2 | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 17 | -0.75 Percentage of HbA1c in blood | Standard Error 0.082 |
| Albiglutide Process 3 | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 17 | -0.84 Percentage of HbA1c in blood | Standard Error 0.082 |
Secondary
Cmax of Albiglutide in the BE Phase
Cmax of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.
Time frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
Population: Albiglutide PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide Process 2 | Cmax of Albiglutide in the BE Phase | 1881.05 ng/mL | Geometric Coefficient of Variation 58.3 |
| Albiglutide Process 3 | Cmax of Albiglutide in the BE Phase | 1743.05 ng/mL | Geometric Coefficient of Variation 49.1 |
Secondary
Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit
ECG parameters include heart rate, QRS interval, QTinterval, QT interval - Bazett correction (QTcB), QT interval - Fridericia correction (QTcF), RR interval, and PR interval. Criteria for values of potential concern were determined by the medical monitors. For the QRS interval, an increase of \>25% when Baseline QRS \>100 milliseconds (msec) and an increase of \>50% when Baseline QRS \<=100 msec was considered to be of clinical concern. For QTcF, a \>=60 msec change from Baseline was considered to be of clinical concern. For the PR interval, an increase of \>25% when Baseline PR \>200 msec and an increase of \>50% when Baseline PR \<=200 msec was considered to be of clinical concern.
Time frame: Week 1 through Week 25
Population: Safety Population. Only those participants available at the specified time points were analyzed. Different par. may have been analyzed at different time points; the overall number of par. analyzed reflects everyone in the Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit | QRS, Increase of > 25% or >50%, n=139, 137 | 1 Participants |
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit | QTcF, >=60 msec, n=139, 137 | 0 Participants |
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit | PR, Increase of > 25% or >50%, n=137, 135 | 0 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit | QRS, Increase of > 25% or >50%, n=139, 137 | 0 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit | QTcF, >=60 msec, n=139, 137 | 0 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit | PR, Increase of > 25% or >50%, n=137, 135 | 0 Participants |
Secondary
Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit
Criteria for values of potential concern were determined by the medical monitors. For hematocrit, a \>0.1 decrease from Baseline was considered to be of clinical concern. For hemoglobin, a \>25 grams per liter (g/L) decrease from Baseline was considered to be of clinical concern.
Time frame: Week 1 through Week 25
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit | Hematocrit >0.1 decrease | 1 Participants |
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit | Hemoglobin >25 g/L | 1 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit | Hematocrit >0.1 decrease | 0 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit | Hemoglobin >25 g/L | 1 Participants |
Secondary
Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit
Vital signs measured included systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate. Criteria for values of potential concern were determined by the medical monitors. For SBP, a decrease or increase \>30 millimeters of mercury (mmHg) from Baseline was considered to be of clinical concern. For DBP, a decrease or increase \>20 mmHg from Baseline was considered to be of clinical concern. For heart rate, a decrease or increase \>30 beats per minute (bpm) was considered to be of clinical concern.
Time frame: Week 1 through Week 25
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | SBP, decrease >30 mmHg | 18 Participants |
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | SBP, increase >30 mmHg | 10 Participants |
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | DBP, decrease >20 mmHg | 19 Participants |
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | DBP, increase >20 mmHg | 7 Participants |
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | Heart rate, decrease >30 bpm | 1 Participants |
| Albiglutide Process 2 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | Heart rate, increase >30 bpm | 5 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | Heart rate, decrease >30 bpm | 4 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | SBP, decrease >30 mmHg | 16 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | DBP, increase >20 mmHg | 8 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | SBP, increase >30 mmHg | 10 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | Heart rate, increase >30 bpm | 4 Participants |
| Albiglutide Process 3 | Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit | DBP, decrease >20 mmHg | 16 Participants |
Secondary
Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase
The presence of anti-albiglutide antibodies after repeat-dose administration was assessed using a qualified enzyme-linked immunosorbent assay. The assay involved screening, confirmation, and titration steps (tiered-testing approach). The number of participants who tested positive for anti-albiglutide antibodies are presented by visit.
Time frame: Baseline, Week 5, Week 9, Week 13, Week 17, and Week 25 (Follow-up)
Population: Safety Population: all par. who received at least 1 dose of study medication. Only those par. available at the specified time points were analyzed (represented by n= X, X in the category titles). Different par. may have been analyzed at different time points, so the overall number of par. analyzed reflects everyone in the Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Process 2 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Baseline, n=139, 140 | 1 Participants |
| Albiglutide Process 2 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Week 5, n=131, 132 | 1 Participants |
| Albiglutide Process 2 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Week 9, n=124, 120 | 0 Participants |
| Albiglutide Process 2 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Week 13, n=119, 122 | 1 Participants |
| Albiglutide Process 2 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Week 17, n=119, 127 | 0 Participants |
| Albiglutide Process 2 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Week 25, n=116, 118 | 0 Participants |
| Albiglutide Process 3 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Week 17, n=119, 127 | 5 Participants |
| Albiglutide Process 3 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Baseline, n=139, 140 | 0 Participants |
| Albiglutide Process 3 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Week 13, n=119, 122 | 3 Participants |
| Albiglutide Process 3 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Week 5, n=131, 132 | 0 Participants |
| Albiglutide Process 3 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Week 25, n=116, 118 | 2 Participants |
| Albiglutide Process 3 | Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase | Week 9, n=124, 120 | 0 Participants |
Secondary
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. Hypoglycemic events are excluded from this table, except for serious adverse events.
Time frame: From the time the participant consented to participate in the study through Visit 28 (Week 25) or the final follow-up visit, for participants who discontinued active participation in the study
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Process 2 | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 106 Participants |
| Albiglutide Process 2 | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 5 Participants |
| Albiglutide Process 3 | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAE | 1 Participants |
| Albiglutide Process 3 | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 91 Participants |
Secondary
Number of Participants With Indicated Adverse Events of Special Interest
Adverse events of special interest included cardiovascular events, hypoglycemic events, pancreatitis events, thyroid events, gastrointestinal (GI) events, diabetic retinopathy events, systemic allergic reactions (SAR), injection site reactions (ISR), and liver events (AEs from investigations and hepatobiliary disorders were considered).
Time frame: From the time the participant consented to participate in the study through Visit 28 (Week 25) or the final follow-up visit, for participants who discontinue active participation in the study
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Process 2 | Number of Participants With Indicated Adverse Events of Special Interest | Any cardiovascular AE | 15 Participants |
| Albiglutide Process 2 | Number of Participants With Indicated Adverse Events of Special Interest | Any hypoglycemic AE | 11 Participants |
| Albiglutide Process 2 | Number of Participants With Indicated Adverse Events of Special Interest | Any thyroid AE | 2 Participants |
| Albiglutide Process 2 | Number of Participants With Indicated Adverse Events of Special Interest | Any GI AE | 36 Participants |
| Albiglutide Process 2 | Number of Participants With Indicated Adverse Events of Special Interest | Any SAR AE | 1 Participants |
| Albiglutide Process 2 | Number of Participants With Indicated Adverse Events of Special Interest | Any ISR AE | 13 Participants |
| Albiglutide Process 2 | Number of Participants With Indicated Adverse Events of Special Interest | Any hepatobiliary AE | 2 Participants |
| Albiglutide Process 2 | Number of Participants With Indicated Adverse Events of Special Interest | Any investigations | 5 Participants |
| Albiglutide Process 2 | Number of Participants With Indicated Adverse Events of Special Interest | Any pancreatitis AE | 0 Participants |
| Albiglutide Process 2 | Number of Participants With Indicated Adverse Events of Special Interest | Any diabetic retinopathy AE | 0 Participants |
| Albiglutide Process 3 | Number of Participants With Indicated Adverse Events of Special Interest | Any investigations | 10 Participants |
| Albiglutide Process 3 | Number of Participants With Indicated Adverse Events of Special Interest | Any cardiovascular AE | 9 Participants |
| Albiglutide Process 3 | Number of Participants With Indicated Adverse Events of Special Interest | Any ISR AE | 7 Participants |
| Albiglutide Process 3 | Number of Participants With Indicated Adverse Events of Special Interest | Any hypoglycemic AE | 7 Participants |
| Albiglutide Process 3 | Number of Participants With Indicated Adverse Events of Special Interest | Any diabetic retinopathy AE | 0 Participants |
| Albiglutide Process 3 | Number of Participants With Indicated Adverse Events of Special Interest | Any thyroid AE | 1 Participants |
| Albiglutide Process 3 | Number of Participants With Indicated Adverse Events of Special Interest | Any hepatobiliary AE | 2 Participants |
| Albiglutide Process 3 | Number of Participants With Indicated Adverse Events of Special Interest | Any GI AE | 32 Participants |
| Albiglutide Process 3 | Number of Participants With Indicated Adverse Events of Special Interest | Any pancreatitis AE | 0 Participants |
| Albiglutide Process 3 | Number of Participants With Indicated Adverse Events of Special Interest | Any SAR AE | 0 Participants |
Secondary
Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17
A complete physical examination was performed at Screening and at Week 17 and included evaluation of the following organ or body systems: skin (including injection site); head; eyes; ears, sose, and throat (ENT); thyroid; respiratory system; cardiovascular system; abdomen (liver, spleen); lymph nodes; central nervous system (CNT); and extremities. The assessment was categorized as improved, no change, worsened, and not done.
Time frame: Screening and Week 17
Population: Safety Population. Only participants analyzed at Week 17 are presented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Head, Eyes, ENT, Improved | 3 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Lymph Nodes, Worsened | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Respiratory system, Improved | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Head, Eyes, ENT, Not done | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | CNS, Improved | 1 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Respiratory system, No Change | 120 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | CNS, Worsened | 1 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Skin, Not done | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Extremities, Improved | 4 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Respiratory system, Not done | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Extremities, No Change | 114 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Cardiovascular system, Improved | 1 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Extremities, Worsened | 2 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Abdomen (Liver and Spleen), Improved | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Extremities, Not done | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Head, Eyes, ENT, No Change | 115 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Thyroid, Improved | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Thyroid, No Change | 120 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Cardiovascular system, No Change | 119 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Thyroid, Worsened | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Abdomen (Liver and Spleen), Worsened | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Thyroid, Not done | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Cardiovascular system, Worsened | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Skin, Improved | 2 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Abdomen (Liver and Spleen), Not done | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Head, Eyes, ENT, Worsened | 2 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Skin, Worsened | 6 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Respiratory system, Worsened | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Lymph Nodes, Improved | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Abdomen (Liver and Spleen), No Change | 120 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Lymph Nodes, Not done | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Cardiovascular system, Not done | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | CNS, No Change | 118 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | CNS, Not done | 0 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Lymph Nodes, No Change | 120 Participants |
| Albiglutide Process 2 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Skin, No Change | 112 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Thyroid, Improved | 0 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Skin, No Change | 117 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Skin, Worsened | 4 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Skin, Not done | 1 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Head, Eyes, ENT, Improved | 0 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Head, Eyes, ENT, No Change | 122 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Head, Eyes, ENT, Worsened | 2 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Head, Eyes, ENT, Not done | 1 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Cardiovascular system, Improved | 0 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Cardiovascular system, Worsened | 0 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Cardiovascular system, Not done | 1 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Respiratory system, Improved | 1 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Respiratory system, No Change | 123 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Respiratory system, Not done | 1 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Abdomen (Liver and Spleen), Improved | 0 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Abdomen (Liver and Spleen), No Change | 121 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Abdomen (Liver and Spleen), Worsened | 3 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Abdomen (Liver and Spleen), Not done | 1 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Lymph Nodes, Improved | 0 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Lymph Nodes, No Change | 123 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Lymph Nodes, Worsened | 0 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Lymph Nodes, Not done | 2 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | CNS, No Change | 122 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | CNS, Worsened | 0 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Extremities, Improved | 1 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Extremities, No Change | 118 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Extremities, Worsened | 4 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Extremities, Not done | 2 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Thyroid, No Change | 123 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Thyroid, Worsened | 0 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Thyroid, Not done | 2 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Skin, Improved | 3 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Cardiovascular system, No Change | 124 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | Respiratory system, Worsened | 0 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | CNS, Improved | 2 Participants |
| Albiglutide Process 3 | Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17 | CNS, Not done | 1 Participants |
Secondary
t1/2 of Albiglutide in the BE Phase
The terminal elimination half-life (t1/2) of albiglutide in the BE Phase was measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.
Time frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
Population: Albiglutide PK Population. Participants with insufficient concentration data or an unestimable terminal elimination rate constant were excluded from analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide Process 2 | t1/2 of Albiglutide in the BE Phase | 106.42 Hours | Geometric Coefficient of Variation 16.3 |
| Albiglutide Process 3 | t1/2 of Albiglutide in the BE Phase | 113.83 Hours | Geometric Coefficient of Variation 22.5 |
Secondary
Tmax and Tlag of Albiglutide in the BE Phase
Time of the maximum observed plasma concentration (tmax) and the observed time prior to the first quantifiable plasma concentration (tlag) of albiglutide in the BE Phase were measured. Blood samples for PK analysis were collected prior to dosing at Baseline and 24 hr, 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.
Time frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
Population: Albiglutide PK Population. Participants with insufficient concentration data or terminal elimination rate constant not estimable were excluded.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Albiglutide Process 2 | Tmax and Tlag of Albiglutide in the BE Phase | tmax, n=85, 80 | 95.50 Hours |
| Albiglutide Process 2 | Tmax and Tlag of Albiglutide in the BE Phase | tlag, n=84, 80 | 0.00 Hours |
| Albiglutide Process 3 | Tmax and Tlag of Albiglutide in the BE Phase | tmax, n=85, 80 | 96.08 Hours |
| Albiglutide Process 3 | Tmax and Tlag of Albiglutide in the BE Phase | tlag, n=84, 80 | 0.00 Hours |
Secondary
Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP)
The trough concentration of albiglutide at Week 5, Week 9, Week 13, Week 17 (EOT), and Week 25 (Follow-up) following multiple-dose administration was estimated. The time and date of sample collection pre-dose was to be recorded.
Time frame: Immediately pre-dose at Week 5, Week 9, Week 13, Week 17 (End of Treatment [EOT]), and Week 25 (Follow-up)
Population: PK Concentration Population (PKCP): participants (par.) in the MDP for whom a PK sample was collected/analyzed. Only par. available at the specified time points were analyzed (n= X, X in the category titles). Different par. may have been analyzed at different time points; the overall number of par. analyzed reflects everyone in the PKCP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide Process 2 | Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Week 13, n=126, 127 | 2352.94 ng/mL | Standard Deviation 984.488 |
| Albiglutide Process 2 | Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Week 17 (EOT), n=123, 125 | 2360.19 ng/mL | Standard Deviation 1005.598 |
| Albiglutide Process 2 | Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Week 9, n=127, 130 | 2420.95 ng/mL | Standard Deviation 1064.204 |
| Albiglutide Process 2 | Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Week 25 (follow-up), n=121, 123 | 28.20 ng/mL | Standard Deviation 291.287 |
| Albiglutide Process 2 | Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Week 5, n=131, 135 | 10.55 ng/mL | Standard Deviation 34.847 |
| Albiglutide Process 3 | Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Week 25 (follow-up), n=121, 123 | 14.45 ng/mL | Standard Deviation 160.245 |
| Albiglutide Process 3 | Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Week 5, n=131, 135 | 8.70 ng/mL | Standard Deviation 25.547 |
| Albiglutide Process 3 | Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Week 9, n=127, 130 | 2519.62 ng/mL | Standard Deviation 911.794 |
| Albiglutide Process 3 | Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Week 17 (EOT), n=123, 125 | 2436.63 ng/mL | Standard Deviation 1089.381 |
| Albiglutide Process 3 | Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP) | Week 13, n=126, 127 | 2356.27 ng/mL | Standard Deviation 987.143 |