Clinical Trials Register

Summary
EudraCT Number:	2010-022111-19
Sponsor's Protocol Code Number:	FDC114615
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:	2010-09-21
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

2010-022111-19

A.3

Full title of the trial

Study FDC114615: Comparative efficacy of DuodartTM plus lifestyle advice versus watchful waiting plus lifestyle advice with step-up therapy to tamsulosin in the management of treatment naïve men with moderately symptomatic benign prostatic hyperplasia and prostate enlargement.

A.3.1

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

Comparative efficacy of DuodartTM versus watchful waiting with step-up therapy to tamsulosin, in the management of treatment naïve men with symptomatic BPH

A.3.2

Name or abbreviated title of the trial where available

CONDUCT

A.4.1

Sponsor's protocol code number

FDC114615

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	GlaxoSmithKline Research and Development Ltd
B.1.3.4	Country	United Kingdom
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	GlaxoSmithKline Research & Development Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline
B.5.2	Functional name of contact point	GSK Clinical Support Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	GlaxoSmithKline, Iron Bridge Road, Stockley Park West
B.5.3.2	Town/ city	Uxbridge
B.5.3.3	Post code	UB11 1BU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44(0)2089904466
B.5.5	Fax number	+44(0)2089904968
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

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	Duodart
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline GmbH & Co. Kg
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	Duodart
D.3.4	Pharmaceutical form	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.3.8	INN - Proposed INN	DUTASTERIDE
D.3.9.1	CAS number	164656-23-9
D.3.9.3	Other descriptive name	DUTASTERIDE
D.3.9.4	EV Substance Code	SUB06430MIG
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	0.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TAMSULOSIN HYDROCHLORIDE
D.3.9.1	CAS number	106463-17-6
D.3.9.4	EV Substance Code	SUB04673MIG
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	0.4
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	Stronazon
D.2.1.1.2	Name of the Marketing Authorisation holder	Actavis UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Stronazon
D.3.4	Pharmaceutical form	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.3.8	INN - Proposed INN	TAMSULOSIN HYDROCHLORIDE
D.3.9.1	CAS number	106463-17-6
D.3.9.4	EV Substance Code	SUB04673MIG
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	0.4
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Benign prostatic hyperplasia

E.1.1.1

Medical condition in easily understood language

Changes or problems with urination, such as;a hesitant, interrupted, weak stream, urgency and leaking or dribbling, more frequent urination, especially at night

E.1.1.2

Therapeutic area

Diseases [C] - Male diseases of the urinary and reproductive systems [C12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10004446
E.1.2	Term	Benign prostatic hyperplasia
E.1.2	System Organ Class	10038604 - Reproductive system and breast disorders

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 efficacy of DUODART treatment plus lifestyle advice in providing superior symptomatic improvement to treatment naïve BPH subjects compared with watchful waiting plus lifestyle advice plus step-up therapy with tamsulosin.

E.2.2

Secondary objectives of the trial

To assess the efficacy of DUODART treatment plus lifestyle advice compared with watchful waiting plus lifestyle advice plus step-up therapy with tamsulosin for the following:
• in providing superior improvement in BPH Impact Index (BII) score to BPH subjects
• in providing superior improvement in BPH-related Health Status (BHS) to BPH subjects
• in reducing clinical progression in BPH subjects
• in reducing BPH-related prostatic surgery in BPH subjects.
• in providing superior improvements in question 1 of the Patient Perception of Study Treatment (PPST) Questionnaire
• in providing superior improvements in question 2 of the Patient Perception of Study Treatment (PPST) Questionnaire
• Proportion of subjects with IPSS improvement of ≥2 points and ≥3 points from
baseline and, separately, ≥25% improvement from baseline
• To assess the safety and tolerability of DUODART.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males aged ≥50 years.
2. A confirmed clinical diagnosis of BPH.
3. International Prostate Symptom Score (IPSS) 8−19 at Visit 1 (screening).
4. Prostate volume ≥30 cc (by transrectal ultrasonography; TRUS).
5. Total serum prostate specific antigen (PSA) ≥1.5 ng/mL at Visit 1 (screening).
6. Willing and able to give signed written informed consent and comply with study
procedures.
7. Fluent and literate in local language with the ability to read, comprehend and record information on the IPSS and BII questionnaires.
8. Able to swallow and retain oral medication.
9. Willing and able to participate in the study for the full 2 years.
10. Men with a female partner of childbearing potential must either agree to use effective contraception or have had a prior vasectomy. Contraception must be used from 2 weeks prior to administration of the first dose of study treatment until at least 5 halflives for the drug plus 3 months to allow clearance of any altered sperm after the last dose of study treatment.

E.4

Principal exclusion criteria

1. Total serum PSA >10.0 ng/mL at Visit 1 (screening).
2. History or evidence of prostate cancer (e.g. positive biopsy or ultrasound within the previous 6 months, suspicious DRE and/or rising PSA).

Excluded medication and therapies
3. Current or any prior use of the following prohibited medications
i. a 5α-reductase inhibitor (finasteride or dutasteride),
ii. anti-cholinergics (e.g. oxybutynin, propantheline)
iii. an alpha-adrenoreceptor blocker (i.e. indoramin, prazosin, terazosin, tamsulosin, alfuzosin and doxazosin) for BPH or LUTS.
iv. any drugs with anti-androgenic properties (e.g. spironolactone, flutamide, bicalutamide, cimetidine, ketoconazole, progestational agents) within the previous 6 months.
v. any drugs noted for gynaecomastia effects, or could affect prostate volume, within 6 months of the Visit 1
vi. any investigational or marketed study drug within 30 days or 5 half-lives, (whichever is longer), preceding the first dose of study treatment.
4. Current use of:
i. any alpha-adrenoreceptor blocker (i.e. indoramin, prazosin, terazosin, tamsulosin, alfuzosin and doxazosin)
ii. anabolic steroids.
iii. drugs known or thought to have an interaction with tamsulosin, e.g. cimetidine and warfarin.
5. Use of phytotherapy for BPH within 2 weeks prior to Visit 1 (screening) and/or predicted to need phytotherapy during the study.
6. Have a known (immediate or delayed) hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study medication or excipients that, in the opinion of the Investigator or GSK contraindicates their participation.
Exceptions for this exclusion criteria 3 – 6 are:
Topical use is permitted (e.g. cream, eye drops, etc )
or any systemic use NOT related to BPH and that has finished more than 7 months ago to ensure that in any case the time since last administration is longer than 7 half-lives

Recent Medical Procedures
7. Previous prostatic surgery (including TURP, balloon dilatation, thermotherapy and stent replacement) or other invasive or minimally invasive procedures to treat BPH.
8. History of flexible/rigid cystoscopy or other instrumentation of the urethra within 7 days prior to Visit 1 (screening). Catheterisation (<10F) is acceptable with no time restriction.

Medical history
9. History of AUR within 3 months prior to Visit 1 (screening).
10. Post-void residual volume >250 mL (suprapubic ultrasound) at Visit 1 (screening).
11. Any causes other than BPH, which may in the judgement of the investigator, result in urinary symptoms or changes in flow rate (e.g. neurogenic bladder, bladder neck contracture, urethral stricture, bladder malignancy, acute or chronic prostatitis, or acute or chronic urinary tract infections).
12. History of ‘first dose’ hypotensive episode on initiation of alpha-1-adrenoreceptor antagonist therapy for hypertension.
13. History of postural hypotension, dizziness, vertigo or any other signs and symptoms of orthostasis, which in the opinion of the investigator could be exacerbated by tamsulosin and result in putting the subject at risk of injury.
14. History of breast cancer or clinical breast examination finding of unclear origin or suggestive of malignancy.
15. History of hepatic impairment or abnormal liver function tests at Visit 1 (screening).
(defined as ALT, AST or alkaline phosphatase >2 times the ULN, or total bilirubin >1.5 times the ULN (unless associated with predominantly indirect bilirubin elevation or Gilbert's syndrome).
16. History of renal insufficiency, or serum creatinine >1.5 times the upper limit of normal at Visit 1 (screening)..
17. Prior history of malignancies (other than basal cell carcinoma or squamous cell carcinoma of the skin) within the past 5 years. Subjects who have had no evidence of the malignancy for ≥5 years are eligible.
18. History of any illness (including psychiatric) that in the opinion of the investigator might confound the results of the study or poses additional risk to the subject.
19. Any unstable, serious co-existing medical condition(s) including, but not limited to, myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to Screening visit; uncontrolled diabetes or peptic ulcer disease which is uncontrolled by medical management.
20. History or current evidence of drug or alcohol abuse within the previous 12 months.
21. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator or GSK Medical Monitor.

E.5 End points

E.5.1

Primary end point(s)

Lower urinary tract symptoms, which is defined as change in IPSS from baseline to Month 24.

E.5.1.1

Timepoint(s) of evaluation of this end point

Month 24

E.5.2

Secondary end point(s)

Change in BPH Impact Index score from baseline.
Change in BPH-related Health Status (BHS) from baseline.
Time to/proportion of subjects with Clinical progression of BPH.

E.5.2.1

Timepoint(s) of evaluation of this end point

Month 24

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

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

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

103

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

LSLV

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero