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The study did not start recruiting as albiglutide would have been withdrawn from the market prior to study end.
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The incidence of Type 2 Diabetes Mellitus (T2DM) is increasing day by day but the treatment options are limited in children and adolescents. Albiglutide, approved for the treatment of T2DM in adult population, is a novel analogue of glucagon-like peptide-1 (GLP-1) with a sufficiently long half-life to permit once a week injection. The study will be conducted in 2 parts: Part A is a single dose pharmacokinetic (PK) study to confirm the dose and safety of albiglutide in pediatric subjects aged 10 to less than 18 years and Part B is a randomized double-blind placebo controlled study to evaluate the safety and efficacy (glycemic control) of albiglutide in the pediatric population. Treatment duration in Part B is 52 weeks (24 weeks double-blind placebo-controlled and 28 weeks open-label during which all subjects will receive albiglutide). Approximately 210 eligible male and female subjects will be included in the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Albiglutide cohort 1: Part A | Experimental | Approximately 12 eligible subjects, aged between 14 to 18 years, will receive a single dose of 30 mg albiglutide post-randomization. |
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| Placebo cohort 1: Part A | Placebo Comparator | Approximately 3 eligible subjects, aged between 14 to 18 years, will receive a single dose of matching placebo post-randomization. |
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| Albiglutide cohort 2: Part A | Experimental | Approximately 12 eligible subjects, aged between 10 to 14 years, will receive a single dose of 30 mg albiglutide post-randomization. |
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| Placebo cohort 2: Part A | Placebo Comparator | Approximately 3 eligible subjects, aged between 10 to 14 years, will receive a single dose of matching placebo post-randomization. |
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| Albiglutide: Part B | Experimental | Approximately 120 eligible subjects, aged between 10 to 18 years, will receive albiglutide 30 mg once weekly post-randomization. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Albiglutide | Drug | 30 mg of lyophilized albiglutide will be delivered from a prefilled dual chamber glass cartridge (DCC). The pen injector system will deliver 0.5 mL albiglutide as a single subcutaneous injection once a week. |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the curve (AUC) of albiglutide: Part A | Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points | Up to 28 days post-dose |
| Maximum Plasma Concentration (Cmax) of albiglutide: Part A | Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points. | Up to 28 days post-dose |
| Apparent clearance (CL/F) of albiglutide: Part A | Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points. | Up to 28 days post-dose |
| Apparent volume of distribution (V/F) of albiglutide: Part A | Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points. | Up to 28 days post-dose |
| Number of subjects with adverse events (AEs): Part A | An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AESI including gastrointestinal events, hypoglycemia, injection site reactions, pancreatitis, medullary thyroid cancer, atrial fibrillation/flutter, and pneumonia etc will also be evaluated. | Up to Week 8 post dose |
| Change from Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 24: Part B |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in fasting Plasma Glucose (FPG): Part B | FPG will be assessed as a measure of glycemic control. | Up to Week 24 |
| Percentage of subjects reaching HbA1c less than 7%: Part B | Subjects reaching HbA1c less than 7% at the end of double-blind phase will be analyzed using logistic regression. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Chicago | Illinois | 60634 | United States | ||
| GSK Investigational Site |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C534611 | rGLP-1 protein |
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| Placebo: Part B | Placebo Comparator | Approximately 60 eligible subjects, aged between 10 to 18 years, will receive matching placebo once weekly post-randomization. |
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| Placebo | Drug | Matching placebo will be delivered from a prefilled dual chamber glass cartridge DCC. The pen injector system will deliver 0.5 mL matching placebo as a single subcutaneous injection once a week. |
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Change in HbA1c values from Baseline will be evaluated at Week 24. The superiority of albiglutide over placebo will be assessed. |
| Up to Week 24 |
| Time to reach maximum plasma concentration (tmax) of albiglutide: Part A | Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points. | Up to 28 days post-dose |
| Time to reach half of the maximum plasma concentration (t1/2) of albiglutide: Part A | Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points. | Up to 28 days post-dose |
| Up to Week 24 |
| Time to hyperglycemia rescue: Part B | Time to hyperglycemia rescue will be measured at specific timeframe. Addition of or adjustment to metformin will be the first option for rescue therapy. | Up to Week 24 |
| Number of subjects with AEs, serious adverse events (SAEs): Part B | An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE. AESI including gastrointestinal events, hypoglycemia, injection site reactions, pancreatitis, medullary thyroid cancer, atrial fibrillation/flutter, and pneumonia etc will be evaluated. | Up to Week 60 |
| Number of hypoglycemic episodes: Part B | Hypoglycaemic events as per American Diabetes Association (ADA) criteria: severe hypoglycaemia, documented symptomatic hypoglycaemia, asymptomatic hypoglycaemia, probable symptomatic hypoglycaemia and pseudo hypoglycaemia. | Up to Week 60 |
| Evaluation of immunogenicity: Part B | Blood samples will be collected at intervals for the determination of anti-albiglutide antibodies. | Up to Week 60 |
| Change from Baseline in serum calcitonin levels: Part B | Blood samples will be collected to measure serum calcitonin. | Up to Week 52 |
| Number of subjects with abnormal clinical laboratory parameters: Part B | Hematological, clinical chemistry and urine parameters will be evaluated. | Up to Week 60 |
| Assessment of Systolic Blood pressure (SBP) and Diastolic Blood Pressure (DBP): Part B | SBP and DBP will be measured in a seated position after at least a 5-minute rest. | Up to Week 60 |
| Assessment of pulse rate: Part B | Pulse rate will be measured in a seated position after at least a 5-minute rest. | Up to Week 60 |
| Number of subjects with abnormal growth and development: Part B | Height, weight, tanner stage, menstrual history, sex hormones will be evaluated. | Up to Week 52 |
| CL/F of albiglutide: Part B | Blood samples will be collected after repeat dose administration of study treatment at indicated time points | Up to Week 24 |
| V/F of albiglutide: Part B | Blood samples will be collected after repeat dose administration of study treatment at indicated time points | Up to Week 24 |
| First-order absorption rate constant(Ka): Part B | Blood samples will be collected after repeat dose administration of study treatment at indicated time points | Up to Week 24 |
| Number of subjects showing covariate relationship between PK and clinical measure of interest: Part B | The relationship between albiglutide PK parameters and covariates will be evaluated graphically and in the population PK model. | Up to Week 24. |
| Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) diabetes module total score: Part B | The diabetes module of the PedsQL is a disease specific instrument used to assess the degree of difficulty youth experience with different aspects of everyday living, including treatment adherence and barriers, diabetes-related worries, and communication with others about diabetes. Scores range from 0 to 100, with a higher PedsQL scores indicating better levels of functioning and quality of life (QOL). | Up to Week 52 |
| Change from Baseline in Children's Depression Inventory 2 Self Report Short Version [CDI 2: SR(S)] | The CDI 2: SR(S) is a revision of the Children's Depression Inventory and is used to evaluate depressive symptoms in children and adolescents. The CDI 2: SR(S) Form contains 12 items and the domains include emotional problems and functional problems, with additional subscales of negative mood/physical symptoms, negative self-esteem, interpersonal problems and ineffectiveness. | Up to Week 52 |
| Morehead City |
| North Carolina |
| 28557 |
| United States |
| GSK Investigational Site | El Paso | Texas | 79935 | United States |
| D004700 | Endocrine System Diseases |