Type 1 diabetes mellitus MedDRA version: 19.0 Level: LLT Classification code 10012594 Term: Diabetes System Organ Class: 100000004861
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Male or female, aged 18 to 30 years, inclusive, with a diagnosis of T1DM with an interval of 28-56 days between the initial diagnosis and the first dose of study drug. Documentation of the diagnosis of T1DM (and not just insulin deficiency), including the date of diagnosis, must be obtained from the diagnosing physician. 2. Currently requires insulin for T1DM treatment, or has required insulin therapy for T1DM (for greater than 7 days between the date of diagnosis and the first dose of study drug Note: subjects currently taking twice daily commercially available pre-mixed insulin will not be eligible. 3. Positive for at least one of the following autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti-GAD) antibody to protein tyrosine phosphatase-like protein (anti-IA-2) or an insulin autoantibody (IAA). Please note: A subject who is positive for IAA and negative for the other autoantibodies will not be eligible if the subject has been using insulin for a total of =7 days. 4. Evidence of residual functioning pancreatic ß-cells as measured by a peak stimulated C-peptide level > 0.20 nmol/L during the Screening MMTT when plasma glucose level is > 3.9 mmol/L (70 mg/dL) and = 11.1 mmol/L (200 mg/dL). Note: the Screening MMTT should not be performed within one week of resolution of a DKA event. 5. Body mass index = 32.0 kg/m2. 6. Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception (i.e., meeting one of the criteria defined below) from at least 14 days prior to the first dose of randomised study medication until the 12-week post-treatment Follow-up visit • Abstinence from penile-vaginal intercourse, when this is the female’s preferred and usual lifestyle • Oral Contraceptive, either combined or progestogen alone • Injectable progestogen • Implants of etonogestrel or levonorgestrel • Estrogenic vaginal ring • Percutaneous contraceptive patches •Intrauterine device or intrauterine system that has a failure rate of less than 1% per year when used consistently and correctly as stated in the product label • Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject. The information on the male sterility can come from the site personnel’s review of subject’s medical records; medical examination of the subject and/or semen analysis; or interview with the subject on his medical history. • Male condom combined with a female diaphragm, either with or without a vaginal spermicide 7. Able and willing to provide written informed consent and to comply with all study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 68 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Severe gastroparesis i.e., requiring therapy within 6 months prior to Screening 2. History of acute or chronic pancreatitis, or considered clinically at significant risk of developing pancreatitis, during the course of the study (e.g. due to symptomatic gallstones, excess alcohol use). 3. History of significant gastrointestinal surgery that in the opinion of the investigator is likely to significantly affect upper gastrointestinal or pancreatic function (e.g. gastric bypass and banding, antrectomy, Roux en Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper gastrointestinal function) 4. Personal history or family history of thyroid medullary carcinoma or multiple endocrine neoplasia type 2 (MEN2) 5. History of cancer that has not been in full remission for at least 3 years before Screening. (A history of squamous cell or basal cell carcinoma of the skin, or treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed) 6. Fasting triglyceride level >750 mg/dL at Screening. Subjects may be re-tested once during screening, and if the value no longer meets the exclusion criterion, the subject can be randomly assigned to treatment 7. Estimated Glomerular Filtration Rate (eGFR LTET 30 mL/min/1.73 m2 (calculated using the Modification of Diet in Renal Disease (MDRD) formula 8. Haemoglobinopathy that may affect proper interpretation of HbA1c 9. Alanine aminotransferase (ALT) >2.5 × upper limit of normal (ULN) and bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin 1 week) in the year following randomisation. 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. Inhaled, intra-articular, and small quantities of non-potent topical corticosteroids are allowed 16. Receipt of any investigational drug within the 30 days or 5 half-lives, whichever is longer, before Screening, a history of receipt of an investigational anti-diabetic drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Determine the effect of albiglutide therapy versus placebo on endogenous insulin secretion over 52 weeks when added to standard of care in subjects with new onset type 1 diabetes mellitus (NOT1DM);Secondary Objective: •To assess the effect of albiglutide versus placebo on plasma glucagon concentration during a MMTT •Determine the percentage of subjects meeting the definition of a responder (defined as having HbA1c = 7.0% and mean daily insulin use < 0.5 units/kg/day) and the percentage of subjects achieving partial remission status (i.e., defined as subjects with Insulin Dose Adjusted A1c (IDAA1C LTET 9.0) •To assess glycaemic control in both treatment groups as measured by HbA1c •Determine differences in total daily insulin dose between treatment groups •Determine any differences in significant hypoglycaemia (i.e., events with plasma glucose < 3.9 mmol/L and/or requiring third party intervention) between treatment groups •Compare glycaemic variability between treatment groups, as measured by 72-hour continuous glucose monitoring (CGM) and 7 point glucose profile •Determine the effect of albiglutide on body weight Please refer to the protocol P24 for further deatils.;Primary end point(s): Mean change from baseline in stimulated (from MMTT) 2 hour plasma C-peptide area under the curve (AUC) at Week 52;Timepoint(s) of evaluation of this end point: Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Mean change from baseline in stimulated 2 hour plasma C-peptide AUC (from MMTT) at Week 16, 28 and Week 64 • Maximum stimulated plasma C-peptide: the highest value at any time point during the MMTT after the subject has ingested the mixed meal at Baseline, Week 16, Week 28, Week 52 and Week 64 • Mean change from baseline in glucagon AUC (from MMTT) at Week 16, 28, 52 and Week 64 • Percent of responders (as defined as subjects with HbA1c Week 24 and greater than Week 52. • Number and magnitude of hypoglycaemic ( 10.0 mmol/L) from the 7 point glucose profile at Baseline, Week 28 and Week 52 • Time spent with a plasma glucose 10.0 mmol/L, respectively as performed by 72-hour CGM at Baseline, Week 28 and Week 52 • Change from Baseline in body weight (kg) at Week 52 and Weight over time (i.e., at Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64) ;Timepoint(s) of evaluation of this end point: See section E.5.2 | — |
Countries
Germany, Italy, United Kingdom
Contacts
Public ContactClincial Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed