Clinical Trials Register

Summary
EudraCT Number:	2009-011980-35
Sponsor's Protocol Code Number:	09PUK/DCsc05
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-08-12
Trial results	Removed from public view

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

UK - MHRA

A.2

EudraCT number

2009-011980-35

A.3

Full title of the trial

Multicentre, randomised, double-blind (double-dummy), active comparator-controlled, phase III study of the efficacy and safety of a single s.c. Diclofenac HPBCD 75mg/1ml injection as compared to a single i.m. Voltarol® 75mg/3ml, in the treatment of acute moderate-to-severe post-surgical pain following dental surgery (impacted 3rd molar removal).

A.4.1

Sponsor's protocol code number

09PUK/DCsc05

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	IBSA Institut Biochimique SA
B.1.3.4	Country	Switzerland
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	No
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	Diclofenac HPBCD 75 mg/ml
D.3.2	Product code	Diclofenac HPBCD 75 mg/ml
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Diclofenac Sodium
D.3.9.1	CAS number	15307-79-6
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
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)	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	No
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.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	Voltarol ® Ampoules
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharmaceuticals UK Ltd.
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	Voltarol
D.3.2	Product code	Voltarol
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Diclofenac Sodium
D.3.9.1	CAS number	15307-79-6
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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)	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	No
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	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

acute moderate-to-severe post-surgical pain from dental surgery (impacted 3rd molar extraction)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	HLT
E.1.2	Classification code	10044049
E.1.2	Term	Dental pain and sensation 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 demonstrate non-inferiority of a single s.c. injection of Diclofenac HPBCD 75 mg/1ml to a single i.m. injection of Voltarol® 75mg/3ml in relieving acute moderate-to-severe pain after dental surgery

E.2.2

Secondary objectives of the trial

To compare the safety and tolerability of Diclofenac HPBCD 75 mg/1ml s.c to Voltarol® 75mg/3ml i.m.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

General
1. Out-patients of both genders.
2. Patients aged ≥ 18 to ≤ 65 years old.
3. Subjects able and willing to give their written consent prior to inclusion in the study.
4. Female subjects of childbearing potential must have a negative urine pregnancy test at screening and inclusion visit (i.e. not status post hysterectomy or tubal ligation) must be using an appropriate method of contraception according to the definition of Note of ICH M3 Guideline (implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence of vasectomised partner) and must be willing to continue using it throughout the entire study period.
5. Subjects must be able to comprehend the full nature and purpose of the study, including possible risks and side effects, to co-operate with the Investigator, to comply with the requirements of the entire study and to return for the required examinations.

Trial specific
6. Patients undergoing surgical extraction of a single fully or partially impacted mandibular 3rd molar requiring bone removal.
7. Patients experiencing moderate to severe post-operative pain, defined as a pain intensity ≥ 50 mm (VAS), within 6 hours from end of surgery.
8. Pre-operative laboratory tests (haematology, blood chemistry, urinalysis), performed within 30 days before inclusion (Visit 1) in the reference ranges or without clinically significant abnormalities as judged by the Investigator.

E.4

Principal exclusion criteria

General
1. Patients refusing to give a written informed consent.
2. Patients not able to understand the purposes of the study.
3. Patients not reliable, according to the investigator’s opinion.
4. Patients with major psychiatric disorders that could compromise the patient’s participation in the study.
5. Patients previously enrolled in this study or having used any investigational drug/device or participated in any clinical trial in the previous 3 months.
6. Employees of the Investigator or study centre (i.e. Principal Investigator, sub-investigator, study coordinators, other study staff, employees, or contractors of each), with direct involvement in the proposed study or other studies under the direction of that investigator and/or study centre, as well as family members of the employees or investigator.
7. Pregnant or breast-feeding women.
8. Alcohol or drug abuse within previous 12 months.
9. Clinically significant or unstable concurrent diseases whose sequeleae or treatment might interfere with the study evaluation parameters.

Trial specific
10. Contra-lateral lower 3rd molar extraction or any other concomitant extraction.
11. Surgery performed under general anaesthesia, or sedation (including nitrous oxide by inhalation).
12. Complications occurring during the surgical procedure or in the period before randomisation as judged by the investigator.
13. Acute local or systemic infection at the time of surgery that could confound the post-surgical evaluation.
14. Patients with clinical signs of gastritis, gastro-duodenal ulcer, GI bleeding. Other GI disturbances or disease that in the opinion of the investigator could be negatively affected by the administration of NSAIDs.
15. Clinical signs or history of coagulation disorders that could be negatively affected by NSAIDs administration.
16. Hepatic or renal impairment.
17. Patients with significant cardiac impairment (i.e. severe heart failure, severe ischemic heart disease) history of cerebrovascular disease (i.e. ictus), history or peripheral arterial disease, uncontrolled hypertension, (i.e. not stable = repeated measurements of systolic pressure > 160 mm Hg or diastolic pressure > 95 mm Hg, despite pharmacological treatment).
18. Hypersensitivity to diclofenac or other NSAIDs or to one of the study medication components.
19. Patients under chronic treatment with topical or systemic analgesics/NSAIDs.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the study will be the pain intensity difference (PID) after 1.5 hours following drug administration. Pain intensity difference (PID) is derived by subtracting each pain intensity score (PI) from the baseline PI score (t0), where PI is assessed by the patient on a 0-100 mm VAS (from 0 = no pain to 100 = worst pain imaginable).

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

double dummy

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.8.3

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

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	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.1.3	Elderly (>=65 years)	No
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	150
F.4.2	For a multinational trial
F.4.2.1	In the EEA	150
F.4.2.2	In the whole clinical trial	150

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

2009-07-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-08-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-03-25

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