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A Study to Evaluate Pharmacokinetics, Safety and Efficacy of Albiglutide in Pediatric Subjects With Type 2 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT03015519
Recruitment Status : Withdrawn (The study did not start recruiting as albiglutide would have been withdrawn from the market prior to study end.)
First Posted : January 10, 2017
Last Update Posted : January 17, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Albiglutide Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo Controlled, Multi-center Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Albiglutide for the Treatment of Type 2 Diabetes Mellitus in Pediatric Patients
Estimated Study Start Date : August 14, 2017
Estimated Primary Completion Date : April 20, 2020
Estimated Study Completion Date : April 20, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Albiglutide

Arm Intervention/treatment
Experimental: Albiglutide cohort 1: Part A
Approximately 12 eligible subjects, aged between 14 to 18 years, will receive a single dose of 30 mg albiglutide post-randomization.
Drug: Albiglutide
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.

Placebo Comparator: Placebo cohort 1: Part A
Approximately 3 eligible subjects, aged between 14 to 18 years, will receive a single dose of matching placebo post-randomization.
Drug: Placebo
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.

Experimental: Albiglutide cohort 2: Part A
Approximately 12 eligible subjects, aged between 10 to 14 years, will receive a single dose of 30 mg albiglutide post-randomization.
Drug: Albiglutide
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.

Placebo Comparator: Placebo cohort 2: Part A
Approximately 3 eligible subjects, aged between 10 to 14 years, will receive a single dose of matching placebo post-randomization.
Drug: Placebo
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.

Experimental: Albiglutide: Part B
Approximately 120 eligible subjects, aged between 10 to 18 years, will receive albiglutide 30 mg once weekly post-randomization.
Drug: Albiglutide
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.

Placebo Comparator: Placebo: Part B
Approximately 60 eligible subjects, aged between 10 to 18 years, will receive matching placebo once weekly post-randomization.
Drug: Placebo
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.




Primary Outcome Measures :
  1. Area under the curve (AUC) of albiglutide: Part A [ Time Frame: Up to 28 days post-dose ]
    Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points

  2. Maximum Plasma Concentration (Cmax) of albiglutide: Part A [ Time Frame: Up to 28 days post-dose ]
    Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points.

  3. Apparent clearance (CL/F) of albiglutide: Part A [ Time Frame: Up to 28 days post-dose ]
    Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points.

  4. Apparent volume of distribution (V/F) of albiglutide: Part A [ Time Frame: Up to 28 days post-dose ]
    Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points.

  5. Number of subjects with adverse events (AEs): Part A [ Time Frame: Up to Week 8 post dose ]
    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.

  6. Change from Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 24: Part B [ Time Frame: Up to Week 24 ]
    Change in HbA1c values from Baseline will be evaluated at Week 24. The superiority of albiglutide over placebo will be assessed.

  7. Time to reach maximum plasma concentration (tmax) of albiglutide: Part A [ Time Frame: Up to 28 days post-dose ]
    Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points.

  8. Time to reach half of the maximum plasma concentration (t1/2) of albiglutide: Part A [ Time Frame: Up to 28 days post-dose ]
    Blood samples will be collected prior to dosing at Baseline and following single-dose administration of albiglutide at indicated time points.


Secondary Outcome Measures :
  1. Change from Baseline in fasting Plasma Glucose (FPG): Part B [ Time Frame: Up to Week 24 ]
    FPG will be assessed as a measure of glycemic control.

  2. Percentage of subjects reaching HbA1c less than 7%: Part B [ Time Frame: Up to Week 24 ]
    Subjects reaching HbA1c less than 7% at the end of double-blind phase will be analyzed using logistic regression.

  3. Time to hyperglycemia rescue: Part B [ Time Frame: Up to Week 24 ]
    Time to hyperglycemia rescue will be measured at specific timeframe. Addition of or adjustment to metformin will be the first option for rescue therapy.

  4. Number of subjects with AEs, serious adverse events (SAEs): Part B [ Time Frame: Up to Week 60 ]
    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.

  5. Number of hypoglycemic episodes: Part B [ Time Frame: Up to Week 60 ]
    Hypoglycaemic events as per American Diabetes Association (ADA) criteria: severe hypoglycaemia, documented symptomatic hypoglycaemia, asymptomatic hypoglycaemia, probable symptomatic hypoglycaemia and pseudo hypoglycaemia.

  6. Evaluation of immunogenicity: Part B [ Time Frame: Up to Week 60 ]
    Blood samples will be collected at intervals for the determination of anti-albiglutide antibodies.

  7. Change from Baseline in serum calcitonin levels: Part B [ Time Frame: Up to Week 52 ]
    Blood samples will be collected to measure serum calcitonin.

  8. Number of subjects with abnormal clinical laboratory parameters: Part B [ Time Frame: Up to Week 60 ]
    Hematological, clinical chemistry and urine parameters will be evaluated.

  9. Assessment of Systolic Blood pressure (SBP) and Diastolic Blood Pressure (DBP): Part B [ Time Frame: Up to Week 60 ]
    SBP and DBP will be measured in a seated position after at least a 5-minute rest.

  10. Assessment of pulse rate: Part B [ Time Frame: Up to Week 60 ]
    Pulse rate will be measured in a seated position after at least a 5-minute rest.

  11. Number of subjects with abnormal growth and development: Part B [ Time Frame: Up to Week 52 ]
    Height, weight, tanner stage, menstrual history, sex hormones will be evaluated.

  12. CL/F of albiglutide: Part B [ Time Frame: Up to Week 24 ]
    Blood samples will be collected after repeat dose administration of study treatment at indicated time points

  13. V/F of albiglutide: Part B [ Time Frame: Up to Week 24 ]
    Blood samples will be collected after repeat dose administration of study treatment at indicated time points

  14. First-order absorption rate constant(Ka): Part B [ Time Frame: Up to Week 24 ]
    Blood samples will be collected after repeat dose administration of study treatment at indicated time points

  15. Number of subjects showing covariate relationship between PK and clinical measure of interest: Part B [ Time Frame: Up to Week 24. ]
    The relationship between albiglutide PK parameters and covariates will be evaluated graphically and in the population PK model.

  16. Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) diabetes module total score: Part B [ Time Frame: Up to Week 52 ]
    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).

  17. Change from Baseline in Children's Depression Inventory 2 Self Report Short Version [CDI 2: SR(S)] [ Time Frame: Up to Week 52 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Between 10 to less than 18 years of age inclusive at the time of screening.
  • Diagnosis of T2DM with HbA1c more than or equal to 7.0% [53 millimole per mole (mmol/mol)] and less than 10.0% (85.8 mmol/mol) assessed at screening. Currently treated with regimen of diet and exercise with or without metformin. Subjects on metformin monotherapy should have been treated for a minimum of 8 weeks prior to randomization on a dose above 1000 milligram per day (mg/day) or prior documented maximum tolerated dose (MTD) less than or equal to 1000 mg/day.
  • FPG less than 240 mg/deciliter (dL) at screening.
  • Fasting C-peptide more than or equal to 0.8 nanogram per milliliter (ng/mL) at screening.
  • Negative central laboratory assays for Glutamic Acid Decarboxylase 65 (GAD-65) and Islet Cell Autoantigen 512 (ICA512) autoantibodies at screening.
  • Body weight more than or equal to 30 kilogram (kg) at screening.
  • Male subjects will be included. Female subjects who have achieved menarche and are of childbearing potential must be practicing adequate contraception for the duration of participation in the study.
  • Signed informed consent of parent or legal guardian and assent as appropriate will be obtained from the child.

Exclusion Criteria:

  • Subjects with Type 1 diabetes mellitus or secondary diabetes mellitus (i.e. any type other than T2DM)
  • Female subject is pregnant (confirmed by laboratory testing), planning a pregnancy or lactating.
  • History of cancer that has not been in full remission for at least 3 years before screening.
  • History of thyroid cancer.
  • Personal history or family history of thyroid medullary carcinoma or multiple endocrine neoplasia type 2 (MEN2).
  • History of pancreatitis or considered clinically at significant risk of developing pancreatitis during the course of the study (e.g. due to symptomatic gallstones).
  • Severe gastroparesis within 6 months prior to screening.
  • History of significant gastrointestinal (GI) surgery that in the opinion of the investigator is likely to significantly affect upper GI or pancreatic function.
  • Have a history of at least one episode of diabetic ketoacidosis (DKA) after receiving anti-diabetic medication.
  • Fasting triglyceride level more than 750 mg/dL at screening.
  • Serum calcitonin more than 50 picogram (pg/mL) at screening.
  • Hemoglobinopathy that may affect determination of HbA1c.
  • Uncontrolled hypertension at screening.
  • Estimated Glomerular Filtration Rate (eGFR) less than 90 mL/minute/1.73 meter^2 (calculated using the Schwartz equation) at screening.
  • ALT more than 2.5x upper limit of normal (ULN) or Bilirubin more than 1.5xULN (isolated bilirubin more than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin more than 35%) at screening.
  • 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).
  • Current or previous insulin therapy used for more than 4 weeks (continuously) in the 3 months prior to screening.
  • Use of a GLP-1receptor agonist at study entry and during the study.
  • Any oral diabetic medications, except metformin, at study entry and during the study.
  • Use of oral or systemically injected glucocorticoids is generally not allowed within the 3 months before randomization; however, short courses of oral steroids (single dose or multiple doses for up to 7 days) may be permitted provided these cases are discussed with the medical monitor.
  • Weight loss medications.
  • Antiretroviral drugs.
  • Known allergy or serious hypersensitivity reaction to albiglutide or any product components (including yeast and human albumin), any other GLP 1 analogue, insulin, or other study medication's excipients or other contraindications.
  • Any other reason the investigator deems the subject to be unsuitable for the study or may interfere with trial compliance (e.g. significant medical or psychiatric history).
  • The subject has participated in a clinical trial and has received an investigational product or device 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03015519


Locations
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United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60634
United States, North Carolina
GSK Investigational Site
Morehead City, North Carolina, United States, 28557
United States, Texas
GSK Investigational Site
El Paso, Texas, United States, 79935
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03015519    
Other Study ID Numbers: 200938
First Posted: January 10, 2017    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
GSK716155
Type 2 diabetes mellitus
albiglutide
safety
pediatric
efficacy
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
rGLP-1 protein
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs