Omnic and associated names (tamsulosin hydrochloride)

Public Assessment Report
for paediatric studies submitted in accordance
with Article 46 of Regulation (EC) No1901/2006, as
amended
Omnic / Omnic Ocas / Tamsulosini Hydrochloridum /
Yamanaouchi / Tamsulosin Hydrochloridum / Mapelor /
Mapelor Ocas
tamsulosin hydrochloride
NL/W/0014/pdWS/001
Marketing Authorisation Holder:
Boehringer Ingelheim International GmbH
6 June 2011
Rapporteur: The Netherlands
Finalisation procedure (day 120): 16 October 2010
Date of finalisation of PAR 5 june 2012
Nl/w/0014/PDws/001 CMDh Page 1/10

ADMINISTRATIVE INFORMATION
Invented name of the medicinal
product:
INN (or common name) of the active
substance(s):
Omnic, Omnic Ocas, Tamsulosini Hydrochloridum
Yamanaouchi, Tamsulosin Hydrochloridum ,
Mapelor and Mapelor Ocas
Tamsulosin hydrochloride
MAH: Boehringer Ingelheim International GmbH
Currently approved Indication(s) Lower urinary tract symptoms (LUTS) associated
with benign prostatic hyperplasia (BPH).
Pharmaco-therapeutic group
(ATC Code):
Pharmaceutical form(s) and
strength(s):
G04CA02
capsules (modified release), tablets (controlled
release) and WOWTABs (orodispersible controlled
release tablets)
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I. EXECUTIVE SUMMARY
SmPC and PL changes are proposed in sections 4.2 and 5.1.
Summary of outcome
X Paediatric information clarified: section(s) 4.2, 5.1
II. RECOMMENDATION
The information obtained from the submitted studies is considered important for clinical practice. The
conclusions of these two studies are in contrast with the general opinion reported in literature based on
non comparative studies. It is therefore useful to include the results of these placebo controlled study in
SPC section 4.2 and 5.1.
III. INTRODUCTION
On 2 November 2009 the MAH submitted 2 completed paediatric studies for tamsulosin, in accordance
with Article 46 of Regulation (EC) No1901/2006, as amended, on medicinal products for paediatric use.
A short critical expert overview has also been provided by the MAH.
The MAH stated that the submitted paediatric studies do not influence the benefit risk for tamsulosin and
that there is no consequential regulatory action.
IV. SCIENTIFIC DISCUSSION
IV.1 Information on the pharmaceutical formulation used in the study(ies)
Tamsulosin was provided in capsules with a strength of 0.025 mg , 0.1 mg, and 0.2 mg. The mode of
administration was per os - Contents of 2 capsules sprinkled over a single teaspoonful (5 mL) of
applesauce or yogurt. A spoonful of water was taken after ingesting the applesauce or yogurt.
IV.2 Clinical aspects
1. Introduction
The MAH submitted 2 final reports for tamsulosin:
� 527.51 A Phase IIb/III, multi-centre, double-blind, randomised, placebo controlled, dose
ranging study of tamsulosin hydrochloride (low, medium and high dose) as
treatment in children with neuropathic bladder for three months
� 527.66 An uncontrolled, open-label, titration, long-term safety (up to 12 months) and
efficacy study of tamsulosin hydrochloride in children with neuropathic bladder,
with a randomized pharmacokinetic sub-study investigating low, medium and high
dose ranges
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2. Clinical studies
The two submitted studies are described below.
2.1 A Phase IIb/III, multi-centre, double-blind, randomised, placebo-controlled, dose ranging
study of tamsulosin hydrochloride (low, medium and high dose) as treatment in children with
neuropathic bladder for three months. (527.51/ U09-3267-01)
Objectives: To evaluate the efficacy and safety of a range of doses of tamsulosin hydrochloride as
treatment in children with an elevated detrusor leak point pressure associated with a known neurological
deficit (e.g., spina bifida).
Methodology: Double-blind, randomised, placebo controlled, dose ranging trial stratified by age (2-

geographic region. Hochberg procedure was used to adjust for multiple pair-wise testing against the
placebo group. As a secondary analysis a test of trend in the proportion of responders across the dose
levels was performed. Dichotomous secondary endpoints were analysed with the same method used for
the primary endpoint. Continuous secondary endpoints were analysed using analysis of covariance with
treatment variable and following covariates: age group, concomitant use of anti-cholinergic medication,
geographic region and the baseline value for the continuous endpoint.
Efficacy / clinical pharmacology results:
LPP Response (OT): Of the 135 patients (FAS-LPP) who completed the study, 51 patients were LPP
responders (LPP

Orthostatic Testing: The incidence of orthostatic hypotension was low for the placebo and tamsulosin
HCl patients. None were reported as AEs.
Other endpoints: There were no clinically meaningful trends in clinical laboratory endpoints, hormonal
assay results, visual acuity, and cognitive testing for patients on placebo or tamsulosin HCl, nor did there
appear to be a trend among the tamsulosin HCl treatment groups.
ECG assessments: No ECG findings were noted as clinically significant except for one ECG finding of
mild sinus tachycardia that was reported as an AE in a high dose tamsulosin HCl patient.
Conclusions: Tamsulosin HCl showed no statistically significant difference in efficacy from placebo in
pediatric patients with neuropathic bladder based on the absence of statistical and clinical significance
for all primary and secondary endpoints. The overall response rate for the primary endpoint in the
placebo group was comparable to tamsulosin HCl response rates in low, medium, high dose groups,
respectively. The child’s age group and use of anti-cholinergic medication at baseline were not
associated with LPP response rates. No dose response trend was observed.
Tamsulosin HCl was safe and well tolerated across all treatment groups. There were no new or
unexpected adverse events observed. There was no dose response across safety parameters and there
were few serious or related adverse events and their rates were similar across treatment groups.
Efficacy outcomes of this trial indicate that there is no therapeutic value of tamsulosin HCl as a treatment
for pediatric patients with elevated detrusor leak point pressure associated with a known neurological
deficit.
2.2 An uncontrolled, open-label, titration, long-term safety (up to 12 months) and efficacy
study of tamsulosin hydrochloride in children with neuropathic bladder, with a randomized
pharmacokinetic sub-study investigating low, medium and high dose ranges (527.66/U09-3809-
01).
Objectives: 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.
The PK / PD results have been previously summarized and are provided in a separate report (U07-
3384). PK and Denovo patients have been previously summarized and are provided in a separate report
(U09-3250-01).
This report summarizes results for Rollover patients (patients who entered Study 527.66 from Study
527.51).
Methodology: Open-label, uncontrolled, multicenter, safety study of patients who entered from the
double-blind Study 527.51 (U09-3267-01). These patients were titrated to their individual efficacious
dose level.
No. of subjects:
planned: Planned enrolled: 120; Planned entered: 100
actual: Actual enrolled: 105; Actual entered: 96
Patients from the 527.51 study were continued in this study as part of an open-label rollover; the
numbers above represent the number of Rollover patients.
Diagnosis and main criteria for inclusion:
Children between 2 and 16 years of age with elevated detrusor leak point pressure associated with a
known neurological disorder.
dose: 0.025 mg, 0.05 mg, 0.1 mg, 0.2 mg and 0.4 mg
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Active treatment groups:
Weight (kg) Tamsulosin HCl
Low dose
(0.001 – 0.002 mg/kg)
tamsulosin HCl
Medium dose
(0.002 – 0.004 mg/kg)
9.0 – 12.0 0.025 mg 0.05 mg
12.5 – 25.0 0.025 mg 0.05 mg 0.1 mg
25.1 – 50.0 0.05 mg 0.1 mg 0.2 mg
50.1 – 100.0 0.1 mg 0.2 mg 0.4 mg
Tamsulosin HCl
High dose
(0.004 – 0.008 mg/kg)
mode of admin.: Per os. Content of capsule(s) sprinkled over a spoonful of apple sauce or yogurt (per
Amendment No. 2) taken 30 minutes after breakfast
Duration of treatment: Up to 12 months
Criteria for evaluation:
Efficacy / clinical pharmacology:
Efficacy parameters:
Given that the 527.66 trial was prematurely terminated, the analysis plan was modified since there was
less data collected and analyzed. The following alternative endpoints were analyzed:
Primary: response defined as patients who achieved a decrease in their detrusor leak point pressure
(LPP) to less than 40 cm H2O based upon two confirmatory measurements at the last value on
treatment and LPP measurements over time.
Secondary: change from baseline in LPP; improvement or stabilization of hydronephrosis and / or
hydroureter based upon ultrasound grading at the last value on treatment compared to baseline.
Safety: Physical examination, vital signs measurements (blood pressure, pulse rate, respiration rate),
orthostatic testing, electrocardiogram (ECG), standard laboratory measures, urinalysis, vision, cognitive
testing and adverse events.
Statistical methods: Since limited data was collected due to the premature termination of the trial, it
was not feasible to analyze the efficacy and safety variables according to the protocol. Refer to Section
9.8 for a detail description of the changes to the analysis plan.
Descriptive statistics were used to summarize the efficacy and safety. The primary analysis of LPP
responders included the Full Analysis Set of patients based on last value on treatment (FAS-LPP). All
secondary endpoints were analyzed by last value on treatment.
Results
Efficacy: The Group D-Rollover portion of Study 527.66 was terminated early based on data from Study
527.51 that showed lack of efficacy in reducing LPP to

Safety results: Adverse events: tamsulosin HCl treatment was well tolerated during the study; 44.8% of
patients experienced adverse events during the study, all of which were mild to moderate in intensity.
The most frequently occurring adverse events were urinary tract infection (18.8%), nasopharyngitis
(8.3%), influenza (5.2%), and vomiting (5.2%). There was no apparent relationship between the
incidence of these adverse events and the dose of tamsulosin HCl. These adverse events were not
unexpected in this patient population and were consistent with previous findings for the PK and Denovo
patients.
A total of 3 (3.1%) patients had serious adverse events, none of which were considered related to
tamsulosin HCl treatment; no deaths occurred during the study.
Orthostatic testing: there were no reports of orthostatic hypotension during orthostatic testing or reports
of hypotension.
Clinical laboratory measures: There were no clinically meaningful trends in clinical hematology,
chemistry, or urinary laboratory measures with tamsulosin HCl treatment.
Cognitive measures: no clinically relevant deterioration in cognition measures was observed.
Conclusions: The Group D-Rollover portion of Study 527.66 was terminated early based on data from
placebo-controlled Study 527.51 that showed lack of efficacy in reducing LPP to

2.4 Conclusion on clinical safety
The safety profile of tamsulosin was shown to be good in this population of children presenting with
neuropathic bladder secondary to a known neurological disorder (e.g. spina bifida). The AEs that were
reported were expected, with events such as urinary tract infection being common in this group of patients
due to their inherent medical problems. The adverse events that were associated with tamsulosin
treatment e.g. orthostatic hypotension, were expected and are already reported as adverse drug reactions
in the labeling for tamsulosin in adults patients being treated for BPH. No new safety concerns were
raised from these 2 studies. Subgroup analysis did not show any differences that would require dose
modifications, apart from the weight-based dosing scheme already implemented in these trials to
appropriately control the exposure to tamsulosin in paediatric patients.
3. Benefit-risk balance
No unexpected or unlisted side effects were reported during the 2 studies. It therefore can be concluded
that the safety profile in children is - in general terms - comparable with that known from the elderly patient
population with BPH.
Of more interest is the conclusion of the company that in children suffering with neuropathic bladder,
treatment with tamsulosine is ineffective. Although the results obtained are comparable with those
reported in open, non-controlled studies from literature, this placebo controlled study could not distinguish
between the results obtained with placebo and tamsulosin (in various strengths). This is the first indication
that the use of tamsulosin is not effective in children with neuropathic bladder.
The information obtained from the submitted studies is considered important for the conclusions of the
studies are in contrast with the opinion found in literature. It is therefore useful to include the results of
these placebo controlled study in section 4.2 and 5.1.
V. MEMBER STATES OVERALL CONCLUSION AND
RECOMMENDATION
The information obtained from the submitted studies is considered important because the conclusions of
the studies are in contrast with the opinion found in literature. It is therefore concluded to include the
results of these placebo controlled study in section 4.2 and 5.1 (Annex I).
The MAH requested to submit the type 1B variation for practical reasons after variation NL/W/0014/
pdWS/001 is finalized.
� Overall conclusion / Recommendation
The RMS concluded to mention the results of the studies in the SPC. A few minor changes to the text
were proposed by one of the member states. These were agreed by the Rapporteur and by the MAH.
The proposal to submit the type 1B variation 30 days after the pending variation NL/W/0014/ pdWS/001 is
finalized can be accepted. This applies for the product from both manufacturers.
In the type 1B variation the patient leaflet should be amended as well.
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ANNEX I - Proposed Changes to the SPC and PIL
SPC
4.2 Posology
Paediatric population
The safety and efficacy of tamsulosine in children