Type 1 diabetes mellitus MedDRA version: 14.1 Level: PT Classification code 10012601 Term: Diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Lyxumia
Product Name: Lixisenatide 10 micrograms
Product Code: N/A
Pharmaceutical Form: Injection
INN or Proposed INN: Lixis
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The following inclusion criteria apply to both Part A and B studies: The patient may enter the study if ALL the following criteria apply: • Has provided written informed consent • Type 1 diabetes • Diabetes duration for at least 12 months • Insulin treatment since the diagnosis of diabetes • Age 18-65 years (upper age limit specified for clinical safety as there is limited experience of using lixisenatide beyond 65 years) • Basal-Bolus insulin regimen • HbA1c between 7.0% and 9.0% (inclusive) • Stable insulin dose (within 20%) over 3 months prior to recruitment. Patients on low doses of insulin, who have had a change of insulin dose by >20% over the preceding 3 months maybe included at the discretion of the Principal Investigator. • BMI 4 mmol/l Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 33 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: The following inclusion criteria apply to both Part A and B studies: The patient may not enter the study if ANY of the following apply: • Type 2 diabetes • Maturity Onset Diabetes of the Young (MODY) • Pregnancy or women of childbearing age without adequate contraception • Women who are breast-feeding • Major psychiatric disease including diagnosed eating disorders, history of drug or alcohol abuse • Renal impairment (eGFR = 50 ml/min) • Abnormal liver function tests (> 1.5 x upper limit of the normal range) • Have high blood pressure (>180 mmHg systolic or >100 mmHg diastolic) • Known ischaemic heart disease or heart failure • History of stroke • Patient has received any investigational drug within 30 days prior to screening • Oral steroid treatment 30 days prior to randomisation • Known malignancy or any other condition or circumstance, which, in the opinion of the investigator, would affect the patient’s ability to participate in the protocol • Non-English speakers will be excluded due to the nature and complexity of the hypoglycaemic clamp methodology • Known allergy to the drugs or any of the components • Severe hypoglycaemia requiring 3rd party intervention on more than one occasion in the preceding 12 months • Felt to be unsuitable to participate in the trial in the opinion of the Principal Investigator • Currently taking domperidone, metoclopramide or warfarin The following criterion applies to Part B study only: • (For Part B study), took part in the lixisenatide prandial dose finding Part A study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: There are no secondary objectives for the Part A trial. The secondary objective of the Part B trial is to determine 1) If there is an overall improvement in glycaemic control (blood sugar levels) over 24 hours when lixisenatide is added to insulin 2) If there is an improvement in post prandial (i.e. after a meal) glycaemic status, to determine whether • this is only in participants with residual ß cell function, • this is associated with C-peptide / insulin response to hyperglycaemia (low blood sugar episodes) • this is associated with change in glucagon and counter-regulatory hormone response to hyperglycaemia (low blood sugar episodes). 3) To assess if adding lixisenatide to insulin delays decline in cognitive function with hypoglycaemia There are no secondary objectives for the sub-study. ; Primary end point(s): The primary outcome measure for the Part A study is as follows: The percentage reduction in prandial insulin that, when co-prescribed with lixisenatide (10µg/d), will maintain blood glucose levels within 6-9mmol/l, without any instance of blood glucose level dropping below 4mmol/l. The primary outcome measure for the Part B study is as follows: The change in the percentage of Continuous Glucose Monitoring (CGM) readings between 4 and 10 mmol/l (inclusive) during the 3 hour post-prandial period, before and after treatment with lixisenatide compared to matching placebo. The primary outcome measure for the sub-study is as follows: To develop an algorithm using integrated vital sign monitoring that could be used to improve sensitivity and specificity of hypoglycaemia prediction in patients with type 1 diabetes in the future. ;Timepoint(s) of evaluation of this end point: Baseline results ta | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): There are no secondary end points for the Part A study. The secondary end points for the Part B study are as follows: 1) Difference in area under the curve for glucose during a mixed meal test with and without lixisenatide 2) Change in the percentage of CGM readings above 10 mmol/l (hyperglycaemia) and below 3mmol/l (hypoglycaemia, classified in section 13.6) during the 24-hour period before and after treatment with lixisenatide. 3) Change in counter regulatory hormones during the hypoglycaemic clamp with and without lixisenatide. 4) Comparison in CGM outcomes (defined above) between C-peptide positive and C-peptide negative participants with and without lixisenatide. 5) Comparison in the rate of decline of cognitive function with hypoglycaemia between participants with or without lixisenatide. 6) Differences in C-peptide/insulin response during the meal tolerance test between C-peptide positive and C-peptide negative participants with lixisenatide. 7) Differences in counter regulatory response in the hypoglycaemic clamp between C-peptide positive and C-peptide negative participants with lixisenatide. 8) Differences in insulin dose requirement between lixisenatide and placebo groups 9) Differences in bode weight between lixisenatide and placebo groups. There are no secondary end points for the Part B sub-study. ;Timepoint(s) of evaluation of this end point: Baseline results taken at the randomisation visit will be compared to those results obtained following the two study interventions. | — |
Countries
United Kingdom
Contacts
Public ContactIrene Kennedy
Diabetes Trials Unit, University of Oxford
Outcome results
None listed