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

NCT ID: NCT03015519

Last Updated: 2019-01-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-14
• Study Completion Date: 2020-04-20

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Albiglutide

Intervention Type: 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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Albiglutide

Intervention Type: 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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Albiglutide: Part B

Approximately 120 eligible subjects, aged between 10 to 18 years, will receive albiglutide 30 mg once weekly post-randomization.

Group Type: EXPERIMENTAL

Albiglutide

Intervention Type: 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.

Placebo: Part B

Approximately 60 eligible subjects, aged between 10 to 18 years, will receive matching placebo once weekly post-randomization.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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).

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Morehead City, North Carolina, United States

GSK Investigational Site

El Paso, Texas, United States

Countries

United States

Other Identifiers

200938

Identifier Type: -

Identifier Source: org_study_id