Clinical trial NCT03015519: A Study to Evaluate Pharmacokinetics, Safety and Efficacy of Albiglutide in Pediatric Subjects With Type 2 Diabetes Mellitus
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: GSK716155
Type 2 diabetes mellitus
albiglutide
safety
pediatric
efficacy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-01-10
Enrollment: 0
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: Area under the curve (AUC) of albiglutide: Part A
timeFrame: Up to 28 days post-dose
measure: Maximum Plasma Concentration (Cmax) of albiglutide: Part A
timeFrame: Up to 28 days post-dose
measure: Apparent clearance (CL/F) of albiglutide: Part A
timeFrame: Up to 28 days post-dose
measure: Apparent volume of distribution (V/F) of albiglutide: Part A
timeFrame: Up to 28 days post-dose
measure: Number of subjects with adverse events (AEs): Part A
timeFrame: Up to Week 8 post dose
measure: Change from Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 24: Part B
timeFrame: Up to Week 24
measure: Time to reach maximum plasma concentration (tmax) of albiglutide: Part A
timeFrame: Up to 28 days post-dose
measure: Time to reach half of the maximum plasma concentration (t1/2) of albiglutide: Part A
timeFrame: Up to 28 days post-dose
Secondary outcomes:
measure: Change from Baseline in fasting Plasma Glucose (FPG): Part B
timeFrame: Up to Week 24
measure: Percentage of subjects reaching HbA1c less than 7%: Part B
timeFrame: Up to Week 24
measure: Time to hyperglycemia rescue: Part B
timeFrame: Up to Week 24
measure: Number of subjects with AEs, serious adverse events (SAEs): Part B
timeFrame: Up to Week 60
measure: Number of hypoglycemic episodes: Part B
timeFrame: Up to Week 60
measure: Evaluation of immunogenicity: Part B
timeFrame: Up to Week 60
measure: Change from Baseline in serum calcitonin levels: Part B
timeFrame: Up to Week 52
measure: Number of subjects with abnormal clinical laboratory parameters: Part B
timeFrame: Up to Week 60
measure: Assessment of Systolic Blood pressure (SBP) and Diastolic Blood Pressure (DBP): Part B
timeFrame: Up to Week 60
measure: Assessment of pulse rate: Part B
timeFrame: Up to Week 60
measure: Number of subjects with abnormal growth and development: Part B
timeFrame: Up to Week 52
measure: CL/F of albiglutide: Part B
timeFrame: Up to Week 24
measure: V/F of albiglutide: Part B
timeFrame: Up to Week 24
measure: First-order absorption rate constant(Ka): Part B
timeFrame: Up to Week 24
measure: Number of subjects showing covariate relationship between PK and clinical measure of interest: Part B
timeFrame: Up to Week 24.
measure: Change from Baseline in Pediatric Quality of Life Inventory (PedsQL) diabetes module total score: Part B
timeFrame: Up to Week 52
measure: Change from Baseline in Children's Depression Inventory 2 Self Report Short Version [CDI 2: SR(S)]
timeFrame: Up to Week 52
Other outcomes:
Locations:
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Morehead City
country: United States
facility: GSK Investigational Site
state: North Carolina
city: El Paso
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: