E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029279 |
E.1.2 | Term | Neurogenic bladder |
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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 |
This study also serves as a long-time open-label extension for a 3-Month double-blind study (Study 527.51).
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E.2.2 | Secondary objectives of the trial |
To characterise the pharmacokinetic (PK)/pharmacodynamic (PD) profile and evaluate the safety and efficacy of tamsulosin hydrochloride in children with elevated detrusor leak point pressure associated with a known neurological disorder (e.g., spina bifida) for up to 12 months of treatment. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Yes, there are two groups of patients in this study those that go through the PK sub-study and those that go through the long-time open-label extension part of the study. The first 27 entered into the study will go through the PK sub-study only. |
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E.3 | Principal inclusion criteria |
Signed and dated written informed consent by the parent or guardian and, where appropriate, informed assent by the child, prior to admission into the study in accordance with GCP and the local legislation, has been obtained. Children of either sex; ages two to 16 years inclusive with a body weight between nine and 100 kg. However, only patients with a body weight of more than 12 kg will be allowed to participate in the PK section. Neuropathic bladder secondary to known neurological disorder (e.g., spina bifida). This includes patients who are performing clean intermittent catheterization (CIC). Elevated detrusor leak point pressures (LPP) ≥40 cm H2O confirmed by two measurements at baseline (for patients who participated in Study 527.51 the baseline value from that study will be used). An LPP recorded while on stable medication and within 3 months prior to starting this study will be allowed as the baseline measurement if this recording is confirmed by two measurements.
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E.4 | Principal exclusion criteria |
Clinically significant abnormalities found at, or before entering the study [i.e., abnormal vital signs (e.g., hypotension, abnormal ECG)], as well as significant findings during the physical examination, as determined by the investigator. Clinically significant conditions which, in the opinion of the investigator, may put patients at risk because of participation in the study or may influence either the results of the study or the patient’s ability to participate in the study. These clinically significant conditions include, but are not limited to, the following: gastrointestinal, cardiovascular, hepatic, renal, hematologic, metabolic (including uncontrolled diabetes mellitus), immunological, hormonal disorders, respiratory disease or cancer. A history of relevant orthostatic hypotension, fainting spells or blackouts. Postural symptoms occurring (e.g., light-headedness, dizziness, and fainting) with or without a change in blood pressure and/or pulse rate within 6 weeks of Visit 1. Patients with clinically significant laboratory abnormalities, or values greater than 2x times the upper limit of normal range. Severe hydronephrosis (greater than Grade 3, see Section 5.1.2). A renal ultrasound performed within 3 months prior to entering the study will be acceptable as baseline assessment, if this assessment was performed while the patient was on stable medication. Patients who have a history of bladder neck surgery, bladder augmentation or exteriorized bladder drainage procedure and those who had a surgical procedure under general anesthesia within the last 30 days prior to Visit 1 (screening). Patients who have a significant psychiatric disorder that prevents their ability to comply with the protocol. Patients on drug therapy or non-drug therapy (including electro-stimulation) for their neuropathic bladder initiated during the 4 weeks prior to screening. Patients taking cimetidine, ranitidine or warfarin. Patients who have a history of allergy/hypersensitivity (including drug and sulpha allergy) which is deemed relevant to the trial as judged by the investigator. Use of alpha-blockers (e.g., terazosin, alfuzosin, doxazosin and tamsulosin) within 30 days of screening visit, except for patients who participated in tamsulosin Study 527.51 who may have been randomized to tamsulosin. Patients having a symptomatic urinary tract infection (UTI) at screening. Patients may be entered into the study after UTI has been treated and stabilized (i.e., patients are no longer symptomatic). Participation in another trial with an investigational drug within 1 month prior to administration or during the trial, excluding those patients who have participated in tamsulosin Study 527.51. A positive pregnancy test or patients who are lactating. All female patients of child bearing potential, who are sexually active in the opinion of the investigator, must use two accepted methods of birth control. All patients, whose parents and/or guardians in the investigator’s opinion cannot understand the terms of the informed consent form and/or patient information form.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is response defined as patients who achieve a detrusor leak point pressure (LPP) to less than 40 cm H2O based upon two confirmatory measurements at the end of treatment. |
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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 | Yes |
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 | No |
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 | 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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |