Clinical Trials Register

Summary
EudraCT Number:	2012-003159-12
Sponsor's Protocol Code Number:	8405011
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-08-22
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2012-003159-12

A.3

Full title of the trial

Efficacy of propiverine hydrochloride extended release (ER) 45 mg in patients with neurogenic detrusor overactivity – an active-controlled single center crossover trial

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Efficacy of propiverine in patients with neurogenic detrusor overactivity

A.4.1

Sponsor's protocol code number

8405011

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	APOGEPHA Arzneimittel GmbH
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	APOGEPHA Arzneimittel GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	APOGEPHA Arzneimittel GmbH
B.5.2	Functional name of contact point	Cornelia Feustel
B.5.3	Address:
B.5.3.1	Street Address	Kyffhäuserstr. 27
B.5.3.2	Town/ city	Dresden
B.5.3.3	Post code	01309
B.5.3.4	Country	Germany
B.5.4	Telephone number	+493513363529
B.5.5	Fax number	+493513363479
B.5.6	E-mail	cfeustel@apogepha.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Mictonorm Uno
D.2.1.1.2	Name of the Marketing Authorisation holder	Apogepha Arzneimittel GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Modified-release capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	PROPIVERINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB04087MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	45
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Mictonorm
D.2.1.1.2	Name of the Marketing Authorisation holder	Apogepha Arzneimittel GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	PROPIVERINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB04087MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

neurogenic detrusor overactivity

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10012547
E.1.2	Term	Detrusor hyperreflexia
E.1.2	System Organ Class	100000004857

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to compare the efficacy of propiverine hydrochloride ER 45 mg s.i.d. versus propiverine hydrochloride IR 15 mg t.i.d. in patients with NDO in terms of percent change of bladder volume at first detrusor contraction in relation to the baseline value measured after the run-in phase.

E.2.2

Secondary objectives of the trial

The secondary objectives are to compare the efficacy of the study medication (Test vs. Reference) assessed by additional cystometric and clinical parameters and to assess the tolerability of propiverine hydrochloride ER 45 mg s.i.d. vs. propiverine hydrochloride IR 15 mg t.i.d. in patients with NDO. The secondary variables will also be reported in terms of relative change from baseline, if applicable.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Patients with stable neurogenic detrusor overactivity (NDO) due to spinal cord injuries.
2.Ability to understand the patient information and presence of a personally signed and dated informed consent to participate in the study before completing any study related procedures.
3.Female and male patients aged 18 years or older at the time of consent. The date of signing informed consent is defined as the beginning of the Screening Period.
4.Primarily proven NDO with evidence of reflex detrusor contractions in previous pressure-flow-studies.
5.Ability to practice clean intermittent catheterization (by the patient himself or a nurse/relative) at least 4 to 6 times daily.
6.The patient is co-operative and without time-limit available for the entire study duration.

E.4

Principal exclusion criteria

1.Acute urinary tract infection (≥ 105 bacteria/ml urine) as defined by the investigator.
2.Multiple sclerosis and other systemic neurological disease under unstable conditions leading to voiding and/or bladder storage problems.
3.Botulinum toxin injections into the bladder within the last 12 month.
4.Bladder surgery (e.g. augmentation cystoplasty) or stomata for catheterization
(e.g. Mitrofanoff, Mainz pouch).
5.Sacral nerve stimulation (neuromodulation) or electrostimulation therapy within the last 4 weeks before randomization into the study.
6.Presence of bladder or ureteral stones.
7.Surgeries of the lower genitourinary tract within the last 6 months before randomization (e.g. prostatectomy, hysterectomy, tumor surgery) that endanger the integrity of the study in the opinion of the investigator.
8.Medical history of previous radiotherapy of the bladder, prostate, or pelvis.
9.Medical history of cancer of the bladder, prostate, or pelvis that endanger the integrity of the study in the opinion of the investigator.
10.Anomalies of the lower genitourinary tract (e.g. ectopic ureters, fistulas, urethral stenosis) that endanger the integrity of the study in the opinion of the investigator.
11.Medical history of cardiac insufficiency (NYHA stage IV).
12.Evidence of severe renal, hepatic or metabolic disorders that endanger the integrity of the study in the opinion of the investigator and/or that are confirmed by clinical significant laboratory results.
13.Medical history of pre-existing medical contraindications for antimuscarinics (e.g. obstruction of the bowel, Barrett syndrome, toxic megacolon, severe colitis ulcerosa, bladder or intestinal atony, significant degree of bladder outflow obstruction where urinary retention may be anticipated, pollakiuria of cardiac or renal genesis, tachyarrhythmia, angle-closure glaucoma, myasthenia gravis).
14.Known hypersensitivity to propiverine hydrochloride or excipients contained in the trial medication (e.g. lactose monohydrate, coloring agent cochineal red), respectively.
15.Concomitant medication known to have a potential to interfere with the trial medication or the goals of the trial (see section 8.4.6).
16.Pregnant or breast-feeding women or women of childbearing potential without using any reliable contraceptive methods.
17.Patients with impaired co-operation or who are unable to understand the nature, scope and possible consequences of the study.
18.Current or history of impaired renal function as indicated by clinically significantly abnormal creatinine or urea values and abnormal creatinine clearance calculated with the Larsson formula.
19.Participation in another clinical trial with an investigational medicinal product within the last month prior to randomization.
20.An inability to swallow all investigational medicinal products.

E.5 End points

E.5.1

Primary end point(s)

Relative change of bladder volume at first detrusor contraction (reflex volume) in relation to the baseline values determined by standardized cystometric measurements after the run-in phase

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 35

E.5.2

Secondary end point(s)

- Maximum detrusor pressure, maximum cystometric capacity, bladder compliance, detrusor pressure at the time of the first detrusor contraction, occurrence of leakage, leak point volume and leak point pressure as determined by standardized cystometric measurement
- Intake and voiding diary: number of voidings and/or clean intermittent catheterizations (CIC), voided and catheterized volume, incontinence episodes, number and size of pads used, fluid intake
- Quality of Life (QoL)
The secondary variables will be reported in terms of percent change from baseline as well, if applicable.

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 35

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

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

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	18
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	2
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	20

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-09-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-09-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-12-16

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