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] - Hormonal diseases [C19] |
MedDRA Classification |
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 assess if sitagliptin can improve the glucagon secretory response to mild hypoglycemia in elderly patients with metformin-treated type 2 diabetes. |
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E.2.2 | Secondary objectives of the trial |
To assess if sitagliptin can improve the cotisol, eipnephrine, norepinephrine and glucose counterregulatory responses to mild hypoglycemia in edlerly patients with metformin-treated T2DM. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written consent has been given.
2. Patients with metformin treated T2DM (metformin dose >=0.5/day and stable during the preceeding 3 months)
3. Age >=65 years.
4. HbA1c 6.0-8.5% (43-67 mmol/mol; inclusive) at visit 1.
5. Ability to complete the study
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E.4 | Principal exclusion criteria |
1. Use of other glucose-lowering therapy than metformin within three months prior to visit 1.
2. A history of any secondary forms of diabetes, e.g., Cushing’s syndrome and acromegaly.
3. Type 2 diabetes, positive GAD antibodies
4. eGFR <60 ml/min
5. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1
6. Any history of recent (<2 weeks) recurrent or severe hypoglycemic episodes.
7. Any history of acute pancreatitis
8. Any history of anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome.
9. Liver disease such as cirrhosis or chronic active hepatitis
10. History of coronary heart disease or heart failure class III or IV
11. Donation of one unit (500 ml) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks.
12. Treatment with growth hormone of chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1.
13. Use of other investigational drugs at visit 1 or within 30 days of visit 1, unsuitable for the study
14. Hypersensitivity to sitagliptin or any compound in the tablet core (microcrystalline cellulose (E460), calcium hydrogen phosphate, anhydrous (E341), croscarmellose sodium (E468), magnesium stearate (E470b) or sodium stearyl fumarate) or in the film coating (poly(vinyl alcohol), macrogol (E3350), talc (E553b), titanium dioxide (E171), red iron oxide (E172) or yellow iron oxide (E172))
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E.5 End points |
E.5.1 | Primary end point(s) |
The effect of sitagliptin on glucagon counter-regulation to hypoglycemia measured as ∆glucagon (min 165-135) and ∆glucagon (min 195-165) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. The effect of sitagliptin compared to placebo on the counter-regulatory hormones cortisol, epinephrine and norepinephrine at the hypoglycemic clamp steps, determined as ∆ for these variables min 165-135 and 195-165, respectively,
2- The effect of sitagliptin compared to placebo on the insulin secretory rate estimated from the C-peptide responses and GLP-1 and GIP levels at the hypoglycemic clamp steps determined as ∆ for these variables min 165-135 and 195-165, respectively.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | 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 | 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 | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |