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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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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 |
The main objective is to investigate whether yohimbine improves insulin secretion during an oral glucose tolerance test in patients with type 2 diabetes carrying the genetic risk variant for ADRA2A rs553668. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to determine the optimal yohimbine dose regarding effect vs. adverse effects, to examine whether daily yohimbine administration affects the treatment response compared with acute doses, to study whether yohimbine is more effective in risk allele carriers for rs553668 compared with non-risk allele carriers, and to study whether yohimbine in addition to insulin could also affect other metabolic parameters. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written informed consent
Males between 18 and 70 years; postmenopausal women below 70 years
C-peptide 0.35-1.8 nmol/L
HbA1c ≤ 80 mmol/mol according to IFCC |
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E.4 | Principal exclusion criteria |
Ongoing treatment with insulin, other injected antidiabetic treatment, or oral antidiabetic treatment except metformin
GAD antibodies
Dysregulated hypertension
Glaucoma
Known coronary artery disease or arrythmia
Known current or previous ventricular or duodenal ulcer
Known anxiety syndrome
Ongoing treatment with alpha- or beta-adrenergic blockers
Creatinine > 130 micromol/L
Liver failure
Mental disability |
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E.5 End points |
E.5.1 | Primary end point(s) |
Improved insulin secretion by 11% in risk allele carriers for ADRA2A rs553668 measured by the insulin levels at 30 minutes during an oral glucose tolerance test. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During dose escalation phase, i.e. within 6 weeks from start of study for each patient. |
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E.5.2 | Secondary end point(s) |
Improved plasma insulin at 0 and 120 minutes during an oral glucose tolerance test. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During dose escalation phase, i.e. within 6 weeks from start of study for each patient. |
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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 | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Dose escalation with two yohimbine doses and one random placebo dose followed by one-week treatment |
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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 | 1 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |