Clinical Trials Register

Summary
EudraCT Number:	2005-004281-17
Sponsor's Protocol Code Number:	191622-517-00
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:	2007-09-19
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

2005-004281-17

A.3

Full title of the trial

A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Response
Study to Evaluate the Safety and Efficacy of a Single Treatment of BOTOX®
(Botulinum Toxin Type A) Purified Neurotoxin Complex Injected into the Prostate
for the Treatment of Lower Urinary Tract Symptoms in Patients due to Benign
Prostatic Hyperplasia

A.4.1

Sponsor's protocol code number

191622-517-00

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Allergan Inc.
B.1.3.4	Country	United States
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	BOTOX®
D.2.1.1.2	Name of the Marketing Authorisation holder	Allergan Pharmaceuticals Ireland
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.3.1	Product name	BOTOX®
D.3.2	Product code	9060X
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intraprostatic use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Botulinium toxin type A (from Clostridium botulinium)
D.3.9.1	CAS number	93384-43-1
D.3.9.2	Current sponsor code	AGN 191622
D.3.9.3	Other descriptive name	Clostridium botulinum Type A Neurotoxin complex (900 kD)
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100 Allergan Unit
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Yes
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	Powder for solution for injection
D.8.4	Route of administration of the placebo	Intraprostatic use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with lower urinary tract symptoms due to Benign Prostatic Hyperplasia

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10004446
E.1.2	Term	Benign prostatic hyperplasia

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the safety and efficacy of a single treatment of 100 U, 200 U, or 300 U BOTOX® compared with placebo injected into the prostate to treat lower urinary tract symptoms in patients due to benign prostatic hyperplasia.

E.2.2

Secondary objectives of the trial

None stated

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male, aged 50 years and older
2. Weight at least 50 kg or 110 lbs
3. Lower urinary tract symptoms in patients due to benign prostatic hyperplasia based on medical history and digital rectal exam, respectively.
4. Lower urinary tract symptoms (except incontinence) for at least 3 months by patient report. These symptoms may include any or all of the following obstructive or irritative symptoms: weak urinary stream, prolonged voiding, abdominal straining, hesitancy, intermittency, incomplete bladder emptying,dribbling, frequency, nocturia, urgency, bladder pain, and dysuria.
5. International Prostate Symptom Score (IPSS) greater than or equal to 12 at the
screening visit (day -14).
6. Total prostate volume by transrectal ultrasound of at least 30 mL but not greater
than 100 mL determined at the screening visit (day -14).
7. Peak urinary flow rate of at least 5 mL/sec, but not greater than 15 mL/sec with
a voided urine volume of at least 125 mL at the screening visit (day -14).
8. Post void residual urine volume less than 200 mL measured by ultrasound or bladder scan at the screening visit (day -14).
9. If engaging in sexual activities, all patients must use a male condom for 3 months post-treatment irrespective of other contraceptive methods (e.g., vasectomy).
Patient with a partner of child-bearing potential must also use a spermicide gel or cream with the male condom, if patient has not had a vasectomy or the female partner is not using an oral, patch, injectable contraceptive or intrauterine device (if she has not had a tubal ligation or hysterectomy).
10. Written informed consent obtained including information regarding the collection, use, disclosure and protection of their personal information or Data Protection consent (European sites only).
11. Patient is registered in the French social security system and fulfils necessary
requirements as required by local law (French sites only).
12. Able and willing to comply with study instructions and visit schedule.

E.4

Principal exclusion criteria

1. Previous prostate surgery, including minimally invasive procedures (e.g., transurethral needle ablation, transurethral microwave therapy)
2. Any prostate biopsy within 6 weeks of the screening visit (day -14). Patients will be allowed to be re-screened a minimum of 6 weeks after a negative biopsy result is documented. All other protocol inclusion and exclusion criteria must be met.
3. Prominent median lobe at the screening visit (day -14), as determined by the investigator’s opinion (e.g., transrectal ultrasound or previous cystoscopy).
4. Previous or current diagnosis of prostate cancer.
5. Patient with a Prostate Specific Antigen (PSA) greater than 10 μg/L may not be enrolled. Patients with a total PSA greater than or equal to 4.0 μg/L and less than or equal to 10 μg/L must have prostate cancer ruled out to the satisfaction of the investigator according to local site practice.
6. Alpha-adrenergic antagonists within 15 days prior to the screening visit (day -14) and patient is unwilling to remain off the medication for duration of the study.
7. Medications in the following classes within 15 days of the screening visit (day -14) and patient is unwilling or unable to remain off chronic use of these medications for the duration of the study.
• Alpha-adrenergic agonists
• Drugs with anticholinergic/antimuscarinic activity if they are indicated for any form of urinary symptoms or bowel disease
• Antispasmodics, including those indicated for gastrointestinal discomfort
8. Medication in the following classes within 90 days of the screening visit (day -14) and throughout the duration of the study.
• 5-alpha-reductase inhibitors
• Androgens
• Drugs with anti-androgenic activity (e.g., spironolactone)
9. Phytotherapy taken for the treatment of prostate diseases or non-specific urinary
symptoms within 30 days of the screening visit (day -14) and throughout the duration of the study.
10. Medications with anti-platelet or anti-coagulant (e.g., including acetylsalicylic acid) effect are prohibited for a minimum of 3 days or longer according to clinical judgment of the investigator, prior to any study treatment until the end of the day of treatment (refer to Section 8.2.2 Prohibited Medications/Treatments for details).
11. Symptomatic prostatitis (acute or chronic) within 12 months of the screening visit (day -14), as determined by patient history.
12. History or evidence of any urologic abnormalities (e.g., urethral stricture), bladder surgery, or disease (other than BPH) that may impact bladder function.
13. Evidence of anal stenosis or stricture or any other condition that may preclude the patient from receiving any administration of study procedures which are performed transrectally.
14. Recurrent urinary tract infections (UTI) defined as 2 or more episodes in the 12
months prior to the screening visit (day -14) or UTI in the last 6 months prior to
randomization/ treatment visit (day 1).
15. Urinary tract infection defined as a bacteriuria count of >10^4 CFU/mL conjoint with leukocyturia >5/hpf at the screening visit (day -14). In addition, patients with a
lower bacteriuria count who, in the opinion of the investigator, have a UTI should also be excluded.
16. Urinary tract infection (symptomatic or asymptomatic) at the treatment visit (day 1), prior to randomization. Asymptomatic urinary tract infection defined as positive nitrites, blood and/or leukocyte esterase on urine dipstick reagent test strip.
17. History or evidence of interstitial cystitis based on the investigator’s opinion.
18. History or evidence of bladder cancer.
19. History or evidence of stones in the bladder are excluded. Patients with current
evidence of asymptomatic stones in the kidney may be enrolled if no active intervention is planned.
20. History or evidence of urinary incontinence not directly related to benign prostatic hyperplasia (e.g., sphincter conditions).
21. Acute urinary retention or previous use of indwelling catheter for urinary
retention within 3 months of the screening visit (day -14), except if urinary
retention was associated with unrelated surgery and/or general/regional/local
anesthesia and has resolved without any further intervention.
22. Urethral instrumentation within 15 days of the screening visit (day -14), including urodynamic assessments (e.g. bladder catheterization).
23. Previous radiation therapy to the pelvis.
24. Patient with hematuria (>5 RBC/hpf) at the screening visit (day -14) or a history
of hematuria is excluded: 1) if the hematuria is due to a pathological condition in the investigator’s opinion, or 2) if the hematuria is uninvestigated.
25. Diagnosis or findings at the screening visit (day -14) consistent with a known
primary neurologic condition known to affect bladder function (e.g. multiple sclerosis, Parkinson’s disease, spinal cord injury, stroke).

Please refer to protocol for criterion 26 to 34.

E.5 End points

E.5.1

Primary end point(s)

Change of International Prostate Symptom Score (IPSS) score from baseline at 12 week visit.

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

Yes

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

E.8.7

Trial has a data monitoring committee

Yes

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	No
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	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
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	60
F.4.2	For a multinational trial
F.4.2.1	In the EEA	175
F.4.2.2	In the whole clinical trial	350

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

2007-10-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-06-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-05-27

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