| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Effect on postural instability of Melatonine and Zolpidem in healthy elderly subjects |
|
| 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 compare the effect of melatonin (Circadin® 2 mg, RAD Neurim Pharmaceuticals EEC Limited; Berkshire, UK) on postural instability with that of placebo when administered as single doses in the evening |
|
| E.2.2 | Secondary objectives of the trial |
| to compare the effect of zolpidem (Zolpidem STADA® 5 mg, STADApharma, Bad Vilbel, Germany) on postural instability with that of placebo when administered as single doses in the evening |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. The subject is able to read and understand the Subject Information and Informed Consent Form.
2. The subject and the clinical study physician have signed a study-specific Informed Consent Form. No study-related procedures, including any screening procedures, may be performed before the clinical study physician has obtained written informed consent from the subject.
3. The subject is a healthy man or woman.
If a man, the subject must:
use two contraceptive methods together with his female partner, if she is of childbearing potential; this combination of contraceptive methods must be used from the start of the clinical study until at least 3 months after the last dose of IMPs. At least one of the contraceptive methods must be a barrier contraceptive method. Contraceptive methods allowed include the following: condoms; diaphragm in combination with a spermicide; intrauterine device (IUD, loop); contraception implants; ”mini pills” (with gestagens only); injectable gestagens; combination hormonal contraceptive methods (tablet, patch, or vaginal ring with both ethinylestradiol and gestagen), OR
not be sexually active at enrolment in the clinical study and accept using two contraceptive methods should he become sexual active during or within 3 months after the last dose of IMP, OR
have been surgically sterilised before inclusion, OR
have a partner who is post-menopausal and has had her last natural menstruation at least 24 months before his inclusion, OR
have a partner who has had a hysterectomy before his inclusion, OR
have a female partner who has been surgically sterilised before his inclusion
If a woman, the subject must:
be post-menopausal and have had her last natural menstruation at least 24 months before her inclusion
4. The subject is 65 years to 75years of age
5. The subject has a BMI 19 kg/m2 and 30 kg/m2 at the Screening Visit
6. The subject has normal vital signs after resting for 5 minutes in supine position
pulse and heart rate as recorded on the ECG: 51 bpm and 100 bpm
systolic blood pressure: 91 mmHg and 150 mmHg
diastolic blood pressure: 51 mmHg and 90 mmHg
7. The subject has normal 12-lead ECG after 10 minutes resting in supine position (in particular QTc < 450 ms)
8. The subject has an orthostatic blood pressure <20 mmHg (based on the difference between supine and standing [1 minute] systolic blood pressure).
9. The subject has clinical laboratory test values within the reference ranges. Borderline values may be accepted if they are, in the opinion of the investigator, not clinically relevant
10. The subject has a normal circadian rhythm, defined as a person who usually wakes between 06:00 and 09:00 and goes to sleep between 21:00 and 24:00
11. The subject is, in the opinion of the investigator, generally healthy based on assessment of medical history, physical examination, vital signs, ECG, and the results of the haematology, clinical chemistry, urinalysis, serology, and other laboratory tests
12. The subject is covered by a Health Insurance System where applicable, and in compliance with the recommendations of national laws in force relating to biomedical research
13. The subject is not under any administrative or legal supervision.
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|
| E.4 | Principal exclusion criteria |
1. The subject has taken disallowed medication within 1 week prior to the first dose of IMP (or within 5 half-lives prior to baseline for any medication ingested, whichever is longer). Disallowed medication is any prescribed medication or over-the-counter (OTC) medication as well as any herbal medicine known to interfere with the metabolic CYP pathways, such as St. John’s Wort (except for hormonal contraceptives or hormonal substitution therapy). Subjects who have taken any non-prescribed systemic or topical medication may still be entered into the study if, in the opinion of the investigator, the medication will not interfere with the study procedures, study results, or compromise safety.
2. The subject weight >136 kg.
3. The subject cannot stand erect and unsupported for more than 2 to 3 minutes or loses balance when standing on a fixed surface with eyes open.
4. The subject has an excessive consumption of beverages on xanthine bases (more than 4 cups or glasses daily).
5. The subject has a presence or history of alcohol abuse defined as alcohol consumption greater than 21 units per week for men and greater than 14 units per week for women (a unit of alcohol is defined as 250 mL of lager/beer, 100 mL of wine, or 25 mL of spirits); or a presence or history of drug abuse within the last 6 months, or a history of substance abuse deemed relevant by the investigator.
6. The subject has taken any investigational products within 3 months prior to baseline.
7. The subject has taken the IMPs earlier in this clinical study.
8. The subject has participated in a previous clinical study with any of the IMPs
9. The subject has known hypersensitivity to the IMP, zolpidem or their excipients.
10. The subject has a history of severe drug allergy or hypersensitivity.
11. The subject has a presence or history of sleep disorder, fainting, cardiovascular diseases, carotid sinus syndrome, relevant dizziness or arrhythmia.
12. The subject is a regular user (used more than once in a week) of hypnotics, tranquiliers or other drugs to induce sleep.
13. The subject has a history of or presence of any clinically relevant immunological, cardiovascular, pulmonary, metabolic, renal, hepatic, gastrointestinal, endocrinological, haematological, dermatological, venereal, neurological, systemic, ocular or psychiatric or infectious disease or other major disorder, or sign of acute illness.
16. The subject has any concurrent illness that may affect the particular target or the metabolism of the IMPs.
17. The subject has had a clinically relevant illness within 4 weeks before the first dose of IMP.
18. The subject has had surgery or trauma with notable blood loss within the last 3 months before the first dose of IMP.
19. The subject has donated blood within 1 month before the first dose of IMP.
20. The subject has tested positive for anti-human immunodeficiency virus (HIV) 1 and 2 antibodies; hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus antibody (anti-HCV-Ab).
21. The subject’s QTc (Bazett’s or Fridericia’s correction) is >450 ms (at the Screening Visit or at the Safety Baseline Visit) as read on the printout of the ECG produced by the ECG equipment and evaluated by the investigator.
22. The subject smokes more than 10 cigarettes daily or uses equivalent of other nicotine-containing products (such as snuff, nicotine patch, nicotine chewing gum, mock cigarette, inhaler, pipe).
23. The subject has tested positive at the Screening Visit or at the day of admission in each Dosing Period (Day 1, 8 and 15) for drugs of abuse (opiates, methadone, cocaine, amphetamines/methamphetamines (including ecstasy), barbiturates, benzodiazepines and cannabinoids).
24. The subject has tested positive at the Screening Visit or at the day of admission in each Dosing Period (Day 1, 8 and 15) for alcohol.
25. The subject has worked on shifts including night duty within 3 weeks before first the first dose of IMP.
26. The subject exercises extensively in his/her normal life, such as marathon running, triathlon, physical sports at a competitive level.
27. The subject is, in the opinion of the investigator, unlikely to comply with the clinical study protocol or is unsuitable for any other reason.
28. The subject cannot be contacted in case of emergency
29. The subject has failed to give written informed consent prior to any procedure related to the clinical study
30. Any subject who is the investigator or any sub-investigator, research assistant, pharmacist, clinical study coordinator, or other staff thereof, directly involved in the conduct of the clinical study
31. Vulnerable subjects (for example subjects kept in detention).
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Postural instability of Melatonine and Zolpidem after a single oral dose of 2 mg Melatonine and 5 mg Zolpidem respectively. |
|
| 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 | 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Compare effect of Melatonine and Zolpidem on postural instability with Placebo |
|
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| 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 | 1 |
| 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 | Information not present in EudraCT |
| 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
|
| LVLS is defined as the End of Trial |
|
| 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 | 2 |
| E.8.9.1 | In the Member State concerned days | |
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