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

NCT03015519 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: 200938
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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

Keywords

GSK716155; Type 2 diabetes mellitus; albiglutide; safety; pediatric; efficacy

Outcome Measures

Primary Outcomes (8)

• 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

  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

Secondary Outcomes (17)

• Change from Baseline in fasting Plasma Glucose (FPG): Part B

  Up to Week 24

• Percentage of subjects reaching HbA1c less than 7%: Part B

  Up to Week 24

• Time to hyperglycemia rescue: Part B

  Up to Week 24

• Number of subjects with AEs, serious adverse events (SAEs): Part B

  Up to Week 60

• Number of hypoglycemic episodes: Part B

  Up to Week 60

Study Arms (6)

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.

Drug: Albiglutide

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.

Drug: Placebo

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.

Drug: Albiglutide

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.

Drug: Placebo

Albiglutide: Part B

EXPERIMENTAL

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

Drug: Albiglutide

Placebo: Part B

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

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.

Albiglutide cohort 1: Part A; Albiglutide cohort 2: Part A; Albiglutide: Part B

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.

Placebo cohort 1: Part A; Placebo cohort 2: Part A; Placebo: Part B

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Chicago, Illinois, 60634, United States

Location

GSK Investigational Site

Morehead City, North Carolina, 28557, United States

Location

GSK Investigational Site

El Paso, Texas, 79935, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

rGLP-1 protein

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2016
• First Posted: January 10, 2017
• Study Start: August 14, 2017
• Primary Completion: April 20, 2020
• Study Completion: April 20, 2020
• Last Updated: January 17, 2019

Record last verified: 2019-01

Locations

US (3)