Pain MedDRA version: 12.1 Level: LLT Classification code 10033371 Term: Pain
Conditions
Interventions
Product Name: E 52862
Product Code: E 52862
Pharmaceutical Form: Capsule*
Current Sponsor code: E52862
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharma
Sponsors
Laboratorios del Dr Esteve S.A
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of single ascending 500 mg, 600 mg and 800 mg doses of E-52862.;Secondary Objective: 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.;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, AUC0-8. 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 | — |
Countries
United Kingdom
Outcome results
None listed