E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 assess the efficacy, safety and tolerability of thymol 4% solution when administered to the ear canal of children diagnosed with mild or moderate AOM compared to placebo.
The subject’s immune profile (MBL, IgG and sub-classes and CRP) will be assessed for exploratory purposes.
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Two years of age or older at randomisation 2. Written informed consent obtained from subject’s parent or legal guardian 3. Confirmed diagnosis of mild to moderate AOM by a ENT specialist (confirmed by an otoscopic examination and tympanometry) 4. Intact tympanic membrane 5. Ability of the parent or legal guardian to understand and comply with the requirements of the protocol
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E.4 | Principal exclusion criteria |
Individuals are excluded from participation in the study if any of the following criteria apply on Day 1 of study.
1. Lacking informed consent 2. Severe AOM (clinical assessment of the ENT specialist and supported by high body temperature (above 39°C) and composite score of TM parameters 9-13, see protocol section 14.4.1 3. History of hypersensitivity to thymol 4. Ear infection during the last 4 weeks prior to randomisation 5. Known renal dysfunction 6. Known hepatic dysfunction 7. Known diabetes 8. Chronic seizure or neurologic disorder 9. Congenital heart disease 10. Chromosomal defects (children with Down’s syndrome) 11. Any known immunosuppressive condition or immune deficiency disease (including HIV infection), or ongoing receipt of any immunosuppressive therapy 12. Anatomical changes in ear and nearby structures, e.g. skeletal abnormalities or persisting changes following a fracture of the base of the skull 13. Cleft palte 14. Ear surgery, especially if artificial implants have been used (does not apply to grommets) 15. Perforated tympanic membrane 16. Grommets in situ 17. Receipt of an investigational product within 30 days prior to enrolment or expected receipt during this study
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E.5 End points |
E.5.1 | Primary end point(s) |
The analysis of efficacy endpoints (response to treatment/healing) will be based on all subjects randomised who complete treatment with investigational medicinal product according to protocol.
Analysis will be performed on the efficacy data collected during visit 1 (baseline), visit 2 (end of treatment visit) and at follow-up visit (visit 3) taking place 5 days + 1 day following last treatment.
Reduction of the composite score at end of treatment and at the end of follow-up will be calculated and compare between treatment groups using appropriate statistical methods as described below:
As a primary efficacy analysis, the proportion of “healing” patients at Visit 2 and Visit 3, as measured using the composite score, where healing is defined as an improvement to ‘Cured’ or ‘Minimal AOM’. The difference between healing proportion of the the test and placebo products will be tested using proportion test (Z-test) at 0.05 level of significance, if the assumptions of normality are satisfied. Nonparametric statistical methodologies will be used when the assumptions of normality are not met. The proportion of “healing” patients, as measured using the composite score, will be compared using a chi-square test.
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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 | 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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
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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 | 4 |
E.8.9.1 | In the Member State concerned days | |