E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 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 evaluate in Muslim patients with T2DM who plan to fast during the Ramadan fasting period:
1. The proportion of patients with at least one HE (Hypoglycaemic event) is lower in the vildagliptin plus metformin arm compared to the gliclazide plus metformin arm during the Ramadan fasting period.
2. The efficacy of vildagliptin plus metformin by testing the hypothesis that the HbA1C reduction with vildagliptin plus metformin is not inferior to that of gliclazide plus metformin from randomisation to the last visit.
The study needs to meet both co-primary objectives to declare positive. |
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E.2.2 | Secondary objectives of the trial |
1. evaluate the proportion of patients with an increase in HbA1c (<=0.3%), taken at visit 3 to the last visit with no HEs during Ramadan in the vildagliptin plus metformin (A) arm versus the gliclazide plus metformin arm (B).
2. evaluate the efficacy of A by testing the hypothesis that the HbA1c reduction with A is superior to that of B from randomisation to the last visit
3. Evaluate HbA1c change, taken at Visit 3 to study end.
4. Evaluate the incidence of severe HEs during Ramadan
5. Evaluate, in a selected sub-group (approx 25 patients/arm), 72h continuous subcutaneous glucose monitoring (CGM, masked to patients) comparing glucose fluctuation during the first 10 days of Ramadan.
6. Evaluate the treatment adherence during Ramadan
7. Evaluate the body weight change taken at Visit 3 to the last visit
8. Evaluate the unscheduled visits to the HCP, at Visit 3 to the last visit
9. Evaluate the number of days fasted during Ramadan
10. Safety and tolerability |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Substudy on evaluation of Glucose fluctuations through Continuous Glucose Monitoring (CGM):
In a subset of about 50 patients (approximately 25 subjects in each arm), 72h continuous glucose monitoring (CGM) will be performed during the first 10 days of Ramadan fasting period at experienced centres.
The CGM data will be downloaded to a computer for evaluation of glucose profiles and
fluctuation. The mean amplitude of glycemic excursions (MAGE) will be used for assessing glucose fluctuations during the day. The MAGE during the day for each patient will be summarised descriptively (with mean, standard deviation, median, minimum and maximum) by treatment and day. A figure indicating the mean MAGE over time (in days) will be shown.
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E.3 | Principal inclusion criteria |
- Confirmed T2DM diagnose
- Plan to fast during Ramadan
-Treated with a combination of a stable dose of metformin and an SU for at least 12 weeks and HbA1c <= 8.5% at Visit 1
- Taking a sulfonylurea treatment less than 3 years prior to Visit 1
- Body mass index (BMI) >= 22 AND <= 45 KG/M2 at Visit 1
Other protocol-defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
-Pregnant or nursing (lactating) women
-History of hypersensitivity to any of the study drugs
-Patients taking any other anti-diabetes drug (oral or injection) other than metformin and an SU component
- Inability to comply with the study procedures or medications
Other protocol-definied exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Proportion of patients experiencing at least one Hypoglycaemic Evenet (HE) during the Ramadan fasting period
2. Change in glycosylated hemoglobin (HbA1c) level from "Baseline" to "endpoint" to test non-inferiority |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. 1 month
2. from baseline to endpoint (average of 21 weeks) |
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E.5.2 | Secondary end point(s) |
1. Proportion of patients without an increase in HbA1c (<=0.3%) with no HE
2. Change in HbA1c from visit 3 to endpoint
3. Number of serious HE during the Ramadan fasting period
4. Mean amplitude of glycaemic excursions (MAGE) to measure glucose fluctuations during the day
5. Change in body weight from pre-Ramadan visit (Visit 3 ) to end of study
6. Treatment adhererence during the Ramadan fasting period
7. Number of unscheduled visit to health care professional
8. Number of days fasted during the Ramadan fasting period
9. Change in HbA1c level from baseline to endpoint to test superiority |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.HbA1c timeframe: From any time within (week -4) to (day-1) before the start of Ramadan fasting period to within 4 weeks post-Ramadan fasting period; HE timeframe: 1month
2. From anytime within (week -4) to (day -1) before the start of Ramadan fasting period to within 4 weeks post-Ramadan fasting period
3. 1 month
4. 10 days
5. From any time within (week-4) to (day -1) before the start of Ramadan fasting period to within 4 weeks post-Ramadan fasting period
6. 1month
7. visit 3 (anytime from week-4 to day-1 before the start of the Ramadan fasting period) to visit 4 (within 4 weeks post-Ramadan fasting period)
8. 1 month
9. from baseline to endpoint (average of 21 weeks) |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Denmark |
Egypt |
Germany |
India |
Indonesia |
Jordan |
Kuwait |
Lebanon |
Malaysia |
Russian Federation |
Saudi Arabia |
Spain |
Sweden |
Tunisia |
Turkey |
United Arab Emirates |
United Kingdom |
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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 | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |