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 | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033371 |
E.1.2 | Term | Pain |
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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 |
To assess the safety and tolerability of single ascending 500 mg, 600 mg and 800 mg
doses of E-52862. |
|
E.2.2 | Secondary objectives of the trial |
To describe the cardiovascular safety profile, including rhythm and conduction
abnormalities, categorical QT/QTc interval data and qualitative and quantitative ECG
variations from baseline.
• To describe and compare the number and the rates of adverse events under each
treatment.
• To describe the pharmacokinetic profiles (PK) of E-52862 and metabolites in the
study population.
• To describe effect response relationship, using a battery of cognitive tests. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Healthy male or female subjects aged between 18 and 35 years (inclusive) at
screening.
2. Signed informed consent in the local language prior to any study-mandated procedure.
3. No clinically significant findings on the physical examination at screening and at
admission on Day −2 of Period 1.
4. Body mass index (BMI) between 18 and 25 kg/m2 (inclusive) at screening and at
admission on Day −2 of Period 1, body weight at least 45 kg.
5. Systolic blood pressure 100–130 mmHg, diastolic blood pressure 60–80 mmHg, and
pulse rate 40–90 bpm (all inclusive), measured on the left arm, after 10 minutes in the
supine position at screening and at admission on Day -2 of Period 1.
6. Triplicate 12-lead ECG without clinically relevant abnormalities measured after 10
minutes in the supine position at screening and at admission on Day -2 of Period 1.
7. 24-hour 5-lead Holter ECG without clinically relevant abnormalities measured at
screening.
8. Haematology, biochemistry, and urinalysis test results not deviating from the normal
range to a clinically relevant extent at screening and at admission on Day -2 of Period
1.
9. The Caucasian subjects should be distinguished especially by very light to brown skin
pigmentation and straight to wavy or curly hair, and should be indigenous to Europe,
northern Africa, western Asia, and India. Therefore, the study may as well include
Caucasian subjects from North America, Australia and South Africa.
10. Subjects must agree to use acceptable methods of contraception |
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E.4 | Principal exclusion criteria |
1. History or clinical evidence of any disease and/or existence of any surgical or medical
condition which might interfere with the absorption, distribution, metabolism or
excretion of the study drug (appendectomy and herniotomy allowed, cholecystectomy
not allowed).
2. History of clinically significant syncope.
3. Family history of sudden death.
4. Family history of premature cardiovascular death.
5. Clinically significant history or family history of congenital long QT syndrome (e.g.
Romano-Ward syndrome, Jervell and Lange-Nielson syndrome) or Brugada's
syndrome.
6. History of clinically significant arrhythmias and ischemic heart disease (especially
ventricular arrhythmias, atrial fibrillation, recent conversion from atrial fibrillation or
coronary spasm).
7. Conditions predisposing the volunteer to electrolyte imbalances (e.g. altered nutritional
states, chronic vomiting, anorexia nervosa, bulimia nervosa).
8.ECG abnormalities in the standard 12-lead ECG (at screening and Day -2 of Period 1) and 24-hour 5-lead Holter ECG (at screening) which in the opinion of the Investigator will interfere with the ECG analysis.
9. Any clinically important abnormalities in rhythm, conduction or morphology of resting
ECG that may interfere with the interpretation of QTc interval changes. This includes
subjects with any of the following (at screening and Day -2 of Period 1):
• Sinus node dysfunction.
• Clinically significant PR (PQ) interval prolongation.
• Intermittent second or third degree AV block.
• Incomplete or complete bundle branch block.
• Abnormal T-wave morphology.
• Prolonged QTcB >450 msec or shortened QTcB <350 msec or family history of
long QT syndrome.
Subject with borderline deviations from these criteria may be included if the deviations do not pose a safety risk, and if agreed between the appointed Cardiologist and the Principal Investigator.
10. Signs and/or symptoms of a clinically relevant acute illness in the 4-week period prior to screening.
11. Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture).
12. Known hypersensitivity to any medicines administered in the trial.
13. Treatment with any prescribed medication during the two weeks prior to first baseline day.
14. Treatment with any over-the-counter (OTC) medications during the two weeks prior to first baseline day.
15. Treatment with vitamins and/or minerals within 48 hours prior to the first baseline day.
16. Treatment with another investigational drug within three months prior to dosing or having participated in more than three investigational drug studies within 1 year prior to dosing.
17. Confirmed positive results from urine drug screen (amphetamines, benzodia
cocaine, cannabinoids, opiates, barbiturates and methadone) or from the alcohol
breath test at screening and on Day −2 of Period 1.
18. History or clinical evidence of alcoholism or drug abuse. Alcohol abuse is defined as regular weekly intake of more than 14 units if female and 21 units if male; drug abuse is defined as compulsive, repetitive and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a reduction in dose will lead to withdrawal symptoms.
19. Excessive caffeine consumption, defined as ≥ 800 mg per day at screening (800 mg = 7 cups of coffee or 16 cups of tea).
20. Chronic use of tobacco (smoking, snuff) or other nicotine containing products ) for at least three months.
21. Loss of 250 mL or more blood within three months prior to screening.
22. Positive results from the hepatitis serology, except for vaccinated subjects, at
screening.
23. Positive results from the HIV serology at screening.
24. Any circumstances or conditions, which, in the opinion of the Investigator, may affect
full participation in the study or compliance with the protocol.
25. Legal incapacity or limited legal capacity at screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Calculations of PK parameters for E-52862 - performed after a single oral dose of E-52862: Cmax, tmax, t½, AUC0-t, AUC0-∞.
ECG Evaluation
The following parameters will be collected and reported:
• Uncorrected QT interval (ms)
• RR interval (ms)
• HR (bpm)
• Qualitative ECG variations to include:
o morphological variations of the P wave and T wave,
o occurrence of a U wave
o occurrence of ventricular arrhythmia.
• Quantitative ECG variations including:
o relative and absolute variations of P interval (ms),
o relative and absolute variations PR interval (ms),
o relative and absolute variations of QRS interval (ms).
Cognitive tests
Which will be summarised using descriptive statistics (arithmetic mean, geometric mean, minimum, median, maximum, SD).
Safety analyses
For all subjects who received at least one dose of randomised investigational product, E-52862 or placebo
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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 | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
PK, PD, escalating dose study |
|
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 | 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) | 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
|
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 | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |