ow dose Glibenclamide in Diabetes - Part A (LEGEND-A)

Phase 1

• Conditions: Type 2 diabetes mellitus.; MedDRA version: 19.0 Level: PT Classification code 10012601 Term: Diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2015-002837-23-GB
• Lead Sponsor: niversity of Oxford

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-04-21
• Study Completion: 2018-02-19
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 16

Inclusion Criteria

1. Diagnosis of T2DM.
2. Age 18 years or over.
3. Diet controlled or on metformin only for diabetic control.
4. Body mass index 40 kg/m2 or less.
5. HbA1c 7.0% to 9.5% (53mmol/mol to 80mmol/mol) inclusive.

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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1.Taking anti-diabetic therapies other than metformin
2.Pregnancy or women of childbearing age without adequate contraception
3.Women who are breastfeeding
4.Major psychiatric disease including diagnosed eating disorders, history of drug or alcohol abuse
5.Known sight-threatening retinopathy
6.Renal impairment (eGFR < 60 ml/min; CKD Stage 3)
7.Abnormal liver function tests (> 1.5 x upper limit of normal range)
8.Known ischaemic heart disease or heart failure
9.Known history of a stroke
10.Known history of porphyria
11.Concomitant use of miconazole or other oral antifungal medication.
12.Known or suspected allergy to trial product or related products
13.Oral steroid treatment 30 days prior to randomisation or at any time during the trial period.
14.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.
15.Ketoacidosis
16.Felt to be unsuitable to participate in the trial in the opinion of the Chief Investigator.
17.Receipt of any investigational trial drug within 3 month prior to participation in the current trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Concentration of plasma glucagon using fasting blood samples prior to each dose change.;Timepoint(s) of evaluation of this end point: Pre-dose blood sampling on day 0, 3, 7, 10, 14, 17 and 21 of the trial.;Main Objective: To identify the dose of glibenclamide that causes a significant decrease in fasting plasma glucagon concentration.;<br> Secondary Objective: 1. To determine whether low doses of glibenclamide can result in an overall improvement in blood glucose control throughout the day.<br><br> 2. To determine the effect low-dose glibenclamide has on fasting glucose, insulin and C-peptide levels.<br><br> 3. To determine the blood level of glibenclamide prior to each dose increase.<br>

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): 1. Change in the mean percentage of Continuous Glucose Monitoring (CGM) readings above 10 mmol/L before starting glibenclamide and prior to each change in dose.<br><br> 2. Concentration of plasma insulin and C-peptide using fasting blood samples prior to each dose change.<br> ;<br> Timepoint(s) of evaluation of this end point: 1. Continuous glucose monitoring readings will be downloaded from the sensor at visits 3 – 9.<br><br> 2. Pre-dose blood sampling on day 0, 3, 7, 10, 14, 17 and 21 of the trial.<br>