E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | Diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To identify the dose of glibenclamide that causes a significant decrease in fasting plasma glucagon concentration. |
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E.2.2 | Secondary objectives of the trial |
1. To determine whether low doses of glibenclamide can result in an overall improvement in blood glucose control throughout the day.
2. To determine the effect low-dose glibenclamide has on fasting glucose, insulin and C-peptide levels.
3. To determine the blood level of glibenclamide prior to each dose increase.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Concentration of plasma glucagon using fasting blood samples prior to each dose change. |
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E.5.1.1 | 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. |
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E.5.2 | 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.
2. Concentration of plasma insulin and C-peptide using fasting blood samples prior to each dose change. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Continuous glucose monitoring readings will be downloaded from the sensor at visits 3 – 9.
2. Pre-dose blood sampling on day 0, 3, 7, 10, 14, 17 and 21 of the trial. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 31 |