| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| A trial on healthy volunteer fore the development of a treatment for cataplexy and excessive daytime sleepiness in narcolepsy. |
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| E.1.1.1 | Medical condition in easily understood language |
Cataplexy is an abrupt temporary loss of voluntary muscular function and tone.
Narcolepsy which is an neurological disorder that affects the control of sleep and wakefulness. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10007738 |
| E.1.2 | Term | Cataplexy and narcolepsy |
| E.1.2 | System Organ Class | 100000004852 |
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| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the pharmacokinetics (PK) and relative bioavailability of a single dose of 6 g FT218 formulation taken 2 hours post-evening meal versus 2 doses of 3 g of Xyrem® administered 4 hours apart, first intake 2 hours post-evening meal in healthy volunteers. |
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| E.2.2 | Secondary objectives of the trial |
| To assess the safety and tolerability of a single dose of 6 g FT218 formulation taken 2 hours post-evening meal versus 2 doses of 3 g of the reference treatment (Xyrem®) administered 4 hours apart, first intake 2 hours post-evening meal, in healthy volunteers. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
The following inclusion criteria must be met for a subject to be eligible for inclusion in the study:
1. Gender: male or female; females may be of childbearing potential, of non childbearing potential, or postmenopausal
2. Age: 18-65 years, inclusive, at screening
3. Body mass index (BMI) : 18.0-28.0 kg/m2
4. Weight : ≥60 kg
5. Status: healthy subjects
6. Race/Ethnicity: “White” (Caucasian)/“Not Hispanic or Latino”
7. Female subjects must be:
• postmenopausal for at least 1 year before the screening visit with follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status, as per PI judgment, OR
• surgically sterile, OR
• if of childbearing potential, agree to practice at least one highly effective method of contraception from the time of signing informed consent through 90 days after the last dose of study drug or complete abstinence during the study if in line with the preferred and usual lifestyle of the subject.
Birth control methods considered as highly effective include:
o Combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation; oral, intravaginal or transdermal
o Progesterone-only hormonal contraception associated with inhibition of ovulation; oral, intravaginal or transdermal
o Hormonal or copper intrauterine device
o Bilateral tubal occlusion
o Vasectomized partner
8. Female subjects of childbearing potential must be non-pregnant and non lactating, and have a negative pregnancy test at screening and each admission to the clinical research center
9. Male subjects, if not surgically sterilized, must agree to use adequate contraception and not donate sperm from first admission to the clinical research center until 90 days after the follow-up visit. Adequate contraception for the male subject is defined as using hormonal contraceptives or an intrauterine device by his female partner. Also, total abstinence, in accordance with the lifestyle of the subject is acceptable
10. Normal blood pressure and heart rate (HR) at the screening visit after 5 minutes in supine position:
• 95 mmHg ≤ systolic blood pressure (SBP) ≤ 140 mmHg
• 50 mmHg ≤ diastolic blood pressure (DBP) ≤ 90 mmHg
• 45 beats per minute (bpm) ≤ HR ≤ 90 bpm
Or considered as not clinically significant as per PI judgment
11. Normal ECG recording on a 12-lead ECG
• 120 < PR < 210 ms
• QRS < 120 ms
• QTc-interval (Fridericia’s) ≤ 430 ms for male and < 450 ms for female
• No signs of sick sinus syndrome
Or considered as not-clinically significant as per PI judgment
12. Laboratory parameters within the normal range of the laboratory (hematological, blood chemistry tests, urinalysis). Individual values out of the normal range can be accepted if judged as not clinically significant by the PI.
13. Medical history without major pathology as judged by the PI
14. All prescribed medication must have been stopped at least 30 days prior to the first admission to the clinical research center. An exception is made for hormonal contraceptives, which may be used throughout the study.
15. All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (eg, St. John’s Wort) must have been stopped at least 14 days prior to each admission to the clinical research center. An exception is made for paracetamol, which is allowed up to admission to the clinical research center
16. No known eating disorder such as hyperphagia or food restriction
17. Willing and able to give written informed consent prior to selection
18. Willing and able to comply with all study mandated requirements and procedures for the duration of the clinical study
19. Willing and able to adhere to all study restrictions including:
• Willingness to comply with the requirement to remain in bed for a minimum of 6 hours after taking the study drug
• Adherence to concomitant drug washout requirements, as applicable, for the duration of the clinical study
• Willing to refrain from operating a car or heavy machinery if determined necessary by the PI
• Willing to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, energy drinks), and grapefruit (juice) from 48 hours prior to each admission to the clinical research center and during the stays in the clinical research center
• Willing to abstain from intensive muscular effort from 96 hours prior to each admission to the clinical research center and during the stays in the clinical research center
• Willing to abstain from smoking or consuming nicotine during the stays in the clinical research center
20. Covered by Health Insurance System
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| E.4 | Principal exclusion criteria |
A subject who meets any of the following exclusion criteria will not be eligible for inclusion in the study:
1. Employee of PRA or the Sponsor
2. The presence of any unstable or clinically significant medical or psychiatric disorders (as determined by medical or psychiatric history, physical examination, and/or clinical laboratory test) which in the opinion of the PI may either put the subject at risk by participation in the study, or may influence the results of the study
3. History of seizure, head trauma, or past-intracranial surgery
4. Any finding in the medical history, physical examination or clinical laboratory tests giving reasonable suspicion of a disease that would contraindicate taking FT218, or a known poor tolerability to the active compound
5. Subjects with a previous history or current ideation of suicide attempt
6. Subjects with a medical diagnosis of Major Depression, as defined by the DSM-IV Criteria for Major Depression Disorder, which in the opinion of the PI would impact subject safety and place the subject at risk by participation in the study
7. Subjects with an O2 saturation of less than 95% at screening or first admission, as measured by pulse oximetry (on room air while fully awake), or subjects with known or suspected respiratory difficulty or any condition that may compromise a subject’s breathing or ability to maintain adequate O2 saturation.
8. Subjects diagnosed with sleep apnea or at high risk for sleep apnea, reporting a history of loud snoring (louder than talking or loud enough to be heard through closed doors), or observed to stop breathing during sleep.
9. Subjects who have a history of drug or alcohol use that, in the opinion of the PI would interfere with study subject safety and adherence to study requirements
10. Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants and alcohol)
11. Occurrence of heartburn, or any surgical intervention (e.g., cholecystectomy) which would be expected to influence the absorption of drugs
12. Frequent headaches and/or migraine, recurrent nausea and/or vomiting
13. Symptomatic hypotension whatever the decrease of blood pressure or asymptomatic postural hypotension defined by a decrease in SBP or DBP ≥ 20 mmHg within 2 minutes when changing from the supine to the standing position
14. Donation or loss of more than 100 mL of blood within 60 days prior to the first drug administration. Donation or loss of more than 1.5 liters of blood (for men) / more than 1.0 liters of blood (for women) in the 10 months prior to the first drug administration in the current study
15. General anesthesia scheduled during the study
16. Known contraindication/allergy/sensitivity/intolerance to the study drug, sodium oxybate, or the inactive ingredients of FT218
17. Subject who cannot be contacted in case of emergency
18. Excessive consumption of beverages with xanthine bases (> 8 cups or glasses/day)
19. Received any known hepatic or renal clearance altering agents for a period of 30 days prior to first drug administration
20. Known hepatitis B surface antigen (HBsAg)-positive status or known or suspected active hepatitis C virus (HCV) infection
21. Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome related illness
22. Subject who, in the judgment of the PI, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development
23. Subject in the exclusion period of a previous study as registered in the applicable databases
24. Subject under administrative or legal supervision
25. Known succinic semialdehyde dehydrogenase deficiency
26. Participation in a drug study within 60 days prior to the first drug administration in the current study. Participation in more than 3 other drug studies (for men) / more than 2 other drug studies (for women) in the 10 months prior to the first drug administration in the current study
27. Significant and/or acute illness within 5 days prior to the first drug administration that may impact safety assessments, in the opinion of the PI
Please note that subjects should refrain from consumption of any foods containing poppy seeds within 48 hours (2 days) prior to screening and each admission to the clinical research center to avoid false positive drug screen results. In addition, they should refrain from strenuous exercise within 96 hours (4 days) prior to screening and each admission as this could result in abnormal clinical laboratory values.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Plasma PK parameters estimated using non-compartmental analysis (NCA), as appropriate: tlag,Cmax, C8h, tmax, λz, t½, AUClast, AUC0-inf, AUC0 8h, AUC%extra, Frel |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1 on Period 1
Day 1 on Period 2 |
|
| E.5.2 | Secondary end point(s) |
| Clinical and laboratory safety: safety will be evaluated based on reported adverse events, physical examination, vital signs, ECG and safety laboratory test results. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Throughout the duration of 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 | 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) | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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 | No |
| 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 | 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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| Defined as the date of the last visit of the last subject. |
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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 | 1 |
| E.8.9.1 | In the Member State concerned days | |
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