| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10015595 |
| E.1.2 | Term | Excessive daytime sleepiness |
|
| 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 determine the effectiveness of VSF-173 compared to placebo in healthy subjects with induced excessive sleepiness (ES) as assessed by the Maintenance of Wakefulness test (MWT). |
|
| E.2.2 | Secondary objectives of the trial |
(1) to assess the effect of VSF-173 compared to placebo on subjective sleepiness as measured by Karolinska Sleepiness Scale (KSS) in healthy subjects with induced ES;
(2) to assess the effect of VSF-173 compared to placebo on objective performance as measured by Psychomotor Vigilance Task (PVT) in healthy subjects with induced ES;
(3) to assess the effect of VSF-173 compared to placebo on mood as measured by a visual analog scale (VAS) in healthy subjects with induced ES;
(4) to assess the safety and tolerability of VSF-173 in healthy subjects. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
General
1. ability and acceptance to provide written informed consent;
2. male or female ≥ 18 and ≤ 40 years old;
3. Body Mass Index [BMI] of > 18 and < 30 kg/m² (BMI = weight (kg)/ [height (m)]²);
4. all women of childbearing potential must be using an acceptable method of birth control (e.g. pill, steroidal contraceptive, IUD, diaphragm or condom with spermicidal jelly or foam, abstinence, surgical sterility, patch, cervical cap) for a period of at least 1 month before dosing and must have negative serum test (minimum sensitivity 25 IU/L of beta-HCG) and must agree to use a double barrier method to prevent pregnancy during the study and for at least three months after the study ends;
5. willing to complete all aspects of the study, and capable of doing so;
Sleep History:
6. between 6 and 9 hrs (inclusive) of sleep per night at least 5 times per week 1 month prior to the screening visit;
7. consistent (within 2 hrs) habitual bedtime and wake time at least 5 times per week 1 month prior to the screening visit;
8. bedtime between 9:30 PM and 12:30 AM at least 5 times per week 1 month prior to the screening visit;
9. between 6 to 9 hrs (inclusive) time in bed for the 5 days prior to Day 1.
Somatic Health
10. good health as determined by the lack of clinically significant deviations from normal in medical history, clinical laboratory determination, ECGs, vital signs and physical examinations conducted during the screening visit;
11. no past or current psychiatric or sleep disorders.
12. subjects must be affiliated with, or a beneficiary of, a French social security system. |
|
| E.4 | Principal exclusion criteria |
Sleep History
1. history or evidence of excessive daytime sleepiness as determined by a score of more than 10 in the Epworth Sleepiness Scale ;
2. history or evidence of sleep apnea as determined by a high-risk score in any two of the three categories in the Berlin Questionnaire ;
3. evidence of insomnia as determined by a score of more than 10 in the Athens Insomnia Scale-5 (AIS-5) ;
4. history or evidence of any other sleep disorder;
5. evidence of daytime nap (per actiwatch) of more than two hrs for the 5 days prior to Day 1.
Medical History
6. history of hypotension or syncope;
7. history of drug induced allergy;
8. history of more than 3 episodes of hives within the last 12 months;
9. history or current evidence of cardiovascular, hepatic, hematopoietic, endocrine, renal, gastrointestinal or metabolic dysfunction;
10. known history of leukopenia or thrombocytopenia;
11. a systolic blood pressure of less than 95 mmHg or greater than 140 mmHg; or a diastolic blood pressure of less than 60 mmHg or greater than 90 mmHg after lying supine for 10 minutes and standing for 3 minutes, or a heart rate less than 50 bpm or more than 90 bpm;
12. loss or withdrawal of one pint (approximately 450 mL) or more of blood within one month before the screening visit;
13. a positive hepatitis B surface antigen (HBsAg) test result;
14. a positive hepatitis C antibody or HIV serology test result;
15. pregnancy or lactation;
16. active disease of the gastrointestinal (GI) system, liver, or kidneys that could result in altered absorption, excess accumulation, or impaired metabolism or excretion of drugs;
17. a history or a current diagnosis of cerebrovascular disease (e.g., stroke, transient ischemic attacks, aneurysms);
18. psychiatric or neurological disorders requiring chronic medication (including but not limited to psychotropic medication) or liable to prejudice subject compliance;
19. unstable, severe, or clinically significant cardiovascular disease (e.g., myocardial infarction in the past 5 years, or unstable angina, cardiac failure [New York Heart Association, Class II or more], or second or third degree atrioventricular block);
20. past history or current diagnosis of seizure disorder;
21. a significant physical illness that requires hospitalization in the 4-week period preceding and during the screening visit;
22. a known exaggerated pharmacological sensitivity or hypersensitivity to NDD094/VSF-173 or fumarate salts;
23. any other medical condition, not previously mentioned, that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical or mental status of the subject to a significant degree or put the subject at special risk;
24. subjects who have participated in a previous NDD094/VSF-173 trials;
Medication Use
25. any subjects who smoke cigarettes or has a urine cotinine greater than 1.2 µmol/L (200ng/mL);
26. consume more than 450 mg of caffeine per day for the 2 weeks preceding Day 1 or consume any caffeine after lunch during screening; The Investigator should be guided by Appendix 12.7 (Caffeine Content of Selected Drugs and Food) to calculate the average subject’s caffeine consumption per day.
27. consume more than 40 g/day of alcohol within the 3 weeks preceding the screening visit;
28. history of drug abuse, known drug addiction or positive test for drug abuse at screening or on Day 1;
29. use of any prescription medications (except for menopausal-related hormone replacement therapy, contraceptives, and non-systemic prescription medication) or sleep aides including herbal or other nontraditional sleep-inducing preparation, within 2 weeks of Day 1 or on Day 1;
30. use of any OTC medication or supplements that could alter the sleep-wake cycle and interfere with the assessment of study medication (See Section 5.5 for examples) within 7 days of Day 1 or on Day 1;
31. recent intake of any of the following substances:
a. an investigational drug, during the three months preceding the screening visit, according to the French National File for Healthy Subjects and/or total annual amount higher than 4500 Euros.
b. a drug treatment known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen), during the four weeks preceding the screening visit.
32. any use of psychotropic drugs.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint will be defined as the average of the 6 post-baseline MWT tests performed every 2 hours during the study. |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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 | 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) | No |
| 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.8.5 | 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
| |
| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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