Clinical Trials Register

Summary
EudraCT Number:	2010-019109-40
Sponsor's Protocol Code Number:	XC0409
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-12-08
Trial 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

Bulgarian Drug Agency

A.2

EudraCT number

2010-019109-40

A.3

Full title of the trial

A multicenter, randomized, observer-blinded, single-dose, placebo-controlled, sequential cohort study of the efficacy and safety of Xen2174 in subjects following bunionectomy surgery

A.3.1

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

Effectiveness and safety of Xen2174 in controlling pain after bunion surgery

A.4.1

Sponsor's protocol code number

XC0409

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	Xenome Ltd
B.1.3.4	Country	Australia
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	Xenome Ltd
B.4.2	Country	Australia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Xenome Ltd
B.5.2	Functional name of contact point	Enquiries
B.5.3	Address:
B.5.3.1	Street Address	PO Box 1024, Indooroopilly Centre
B.5.3.2	Town/ city	Indooroopilly, Queensland
B.5.3.3	Post code	4068
B.5.3.4	Country	Australia
B.5.4	Telephone number	+61 7 3720 8055
B.5.5	Fax number	+61 7 3378 0186
B.5.6	E-mail	enquiries@xenome.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	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	Xen2174
D.3.2	Product code	Xen2174
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intrathecal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	Xen2174
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	12.0
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	Yes
D.3.11.13.1	Other medicinal product type	Synthetic 13-amino acid peptide

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	Intrathecal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderate to severe acute post-operative pain in subjects following primary unilateral first metatarsal bunionectomy

E.1.1.1

Medical condition in easily understood language

Post-operative pain

E.1.1.2

Therapeutic area

Body processes [G] - Bones and nerves physological processes [G11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10028395
E.1.2	Term	Musculoskeletal and connective tissue disorders
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue 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 evaluate the effect of two dose levels of Xen2174 on
the area-under-the-curve of Numeric Rating Scale (NRS) pain
scores in the period 0-48 hours following bunionectomy surgery.

E.2.2

Secondary objectives of the trial

The evaluation of:
• Time to onset of moderate to severe pain following
surgery.
• Opioid consumption during the following periods: 0-48
hours post surgery, Day 3 post surgery, and Week 1 post
discharge (i.e., Day 4 to Day 10 post surgery).
• Assess the safety and tolerability of Xen2174 in the acute
pain setting.
• Explore the dose-effect relationship of Xen2174.
• Evaluate the systemic single-dose pharmacokinetic (PK)
profiles of single-dose IT Xen2174.
• Estimate the duration of efficacy of Xen2174.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Subject is able to read and voluntarily sign the written informed consent document as approved by the Competent Authority, if applicable, and Independent Ethics Committee (IEC), and is given the opportunity to ask questions regarding the study prior to signing the informed consent and performance of any study-specific procedures.
• Subject must require primary unilateral first metatarsal bunionectomy surgery (including osteotomy) to correct hallux valgus
• Subject must be male or female 18-65 years of age.
• Subject is Class ASA 1 or ASA 2 using the American Society of Anesthesiologists Physical Status Classification System.
• If female, subject is non-lactating, and is either:
1. not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;
or
2. of childbearing potential but is not pregnant as confirmed by negative serum pregnancy test at the time of screening, and is practicing one of the following methods of birth control: oral, transdermal or parenteral contraceptives for 3 months prior to Study Drug administration or double-barrier method. If serum pregnancy test results are inconclusive, then the pre-surgical urine pregnancy test will determine eligibility.
• Subject must be willing and able to comply with the protocol, and able to score their pain intensity.
• Subject is in good health as determined by the Investigator on the basis of medical history, physical examination, ECG, and screening laboratory results.
• Subject must be suitable for intrathecal bolus administration of either Xen2174 in a 5% dextrose solution or a 5% dextrose solution (Placebo), with no anatomical or pathological abnormalities that would compromise intrathecal lumbar injection.
• Subject is willing and able to remain at the research center for the entire 3-day Treatment Period.

E.4

Principal exclusion criteria

• Subject is pregnant or lactating.
• Subject has been on an investigational drug within 30 days prior to the initiation of Study Drug.
• Subject has had prior exposure to Study Drug in a previous clinical trial.
• Subject has a condition that would contraindicate the use of opioid analgesia, particularly chronic respiratory compromise.
• Subject is morbidly obese (body mass index ≥ 35 kg/m2 ).
• Subject has chronic respiratory insufficiency.
• Subject is on chronic opioid therapy, or is opioid tolerant in the judgment of the Investigator because of routine opioid use.
• Subject has a known allergy or hypersensitivity to opioids, paracetamol and/or ondansetron.
• Subject has known bleeding disorder or is taking agents affecting coagulation preoperatively [deep vein thrombosis (DVT) prophylaxis is of the Investigator’s choice postoperatively].
• Subject has any other condition or factor, such as an intracranial lesion associated with increased intracranial pressure, cognitive impairment or mental illness, which in the opinion of the Investigator might increase the risk to the subject or that precludes the subject’s ability to adhere to the protocol procedures.
• Subject has a known or suspected history of substance or alcohol abuse within 2 years prior to Screening, or is currently using alcohol, drugs of abuse, or any prescription, or over-the-counter medication, in a manner that the Investigator considers indicative of abuse/dependence.
• Subject tests positive to drug screens – amphetamines, methamphetamines (including MDMA/3,4-methylenedioxymethamphetamine), barbiturates, benzodiazepines, THC/marijuana, cocaine and its metabolites (e.g., benzoylecgonine), morphine and its related metabolites derived from opium (opiates), opioids, methadone, PCP (phencyclidine/phenylcyclohexylpiperidine), tricyclic antidepressants – that cannot be justified by prescription use.
• Subject is receiving central nervous system (CNS) drugs for pain, such as a selective serotonin reuptake inhibitor (SSRI), a selective norepinephrine receptor inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), carbamazepine, or tricyclic amine (TCA) compounds within 1-month prior to Check-In.
[Note: if subject is on stable dose of SSRIs or SNRIs for 6 weeks prior to Screening and for a diagnosis other than relief of pain, then they may be eligible for participation in the trial, providing stable doses of the medications are maintained postoperatively].
• Subject has a documented history of seizure, prior head injury resulting in unconsciousness, or has been prescribed anti-seizure medication.

E.5 End points

E.5.1

Primary end point(s)

Area-under-the-curve of Numeric Rating Scale (NRS) pain
scores in the period 0-48 hours following surgery.

E.5.1.1

Timepoint(s) of evaluation of this end point

Pain scores during the first 48 hours following surgery.

E.5.2

Secondary end point(s)

• Time to onset of moderate to severe pain.
• Total amount of opiate analgesia consumed during the Treatment Period

E.5.2.1

Timepoint(s) of evaluation of this end point

Days 1 through 3 following surgery.

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

Yes

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Sequential cohort

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.8.2.4

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

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

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

The end of the trial is 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

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

150

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

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

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Treatment or care after the subject has ended his/her participation in the trial will be the expected normal treatment of that condition.

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

2010-12-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-03-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-08-01

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