Clinical Trials Register

Summary
EudraCT Number:	2010-019785-90
Sponsor's Protocol Code Number:	D2600C00012
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-07-13
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

Denmark - DHMA

A.2

EudraCT number

2010-019785-90

A.3

Full title of the trial

A Phase IIa, Double-blind, Randomised, Parallel-group, Multi-centre Study to Evaluate the Analgesic Efficacy of 28 Days Oral Administration of AZD2423 Compared to Placebo in Patients with Posttraumatic Neuralgia

A.3.1

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

A study to investigate the analgesic efficacy of AZD2423 compared with placebo after 28 days treatment in patients with posttraumatic neuralgia

A.4.1

Sponsor's protocol code number

D2600C00012

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	AstraZeneca AB
B.1.3.4	Country	Sweden
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	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	N/A
B.5.3.2	Town/ city	N/A
B.5.3.3	Post code	N/A
B.5.3.4	Country	Sweden
B.5.6	E-mail	information.center@astrazeneca.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	AZD2423
D.3.2	Product code	AZD2423
D.3.4	Pharmaceutical form	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.3.9.2	Current sponsor code	AZD2423
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	20 to 50
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	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

Posttraumatic Neuralgia (neuropathic pain)

E.1.1.1

Medical condition in easily understood language

Posttraumatic neuropathic pain

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	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10054095
E.1.2	Term	Neuropathic pain
E.1.2	System Organ Class	10029205 - Nervous system 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 investigate the analgesic efficacy of AZD2423 compared with placebo after 28 days of oral administration in patients with PTN.

E.2.2

Secondary objectives of the trial

1. To investigate the responder rate of patients receiving AZD2423 compared to
placebo in patients with PTN.
2. To investigate the analgesic efficacy of AZD2423 on different components of pain
compared to placebo in patients with PTN.
3. To investigate the effect of AZD2423 on different functional consequences of pain
compared to placebo in patients with PTN.
4. To investigate the PK of AZD2423 in patients with PTN.
5. To investigate the safety and tolerability of AZD2423 in patients with PTN.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of informed consent prior to any study specific procedures
2. Male, or non-pregnant and non-lactating female (18-80 years, inclusive). Women considered to be of non-child bearing potential included in the study must be permanently or surgically sterilised or post menopausal:
-Women will be considered post menopausal if they are amenorrheic for 12 months without an alternative medical cause.
The following age-specific requirements apply:
-Women under 50 years old will be considered post menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range.
-Women over 50 years of age will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments.
Permanent sterilization includes hysterectomy and/or bilateral oopherectomy and/or bilateral salpingectomy but excludes bilateral tubal occlusion.
Women of childbearing potential included in the study must use a contraceptive method capable of achieving a failure rate of less than 1 percent per year when used consistently and correctly such as: cupper IUD, intrauterine levonorgestrel system, medroxyprogesterone depot injections, etonogestrel implants or normal and low dose combination pills. Not acceptable methods includes, but is not restricted to: barrier methods, progesterone pills, non-cupper IUD and coitus interruptus.
3. Neuropathic pain due to peripheral nerve injury caused by trauma or surgery.
Duration of neuropathic pain must be at least three months and at most 5 years.
Complex Regional Pain Syndrome (CRPS) type II is accepted provided that pain is due to a defined nerve injury. Nerve injuries at plexus or root level are excluded.
4. Pain intensity (7 days recall) of 4-9 (inclusive) on NRS - Average Pain (0-10) is required for enrolment. At randomisation a 5-day mean baseline NRS - Average Pain intensity (12 h recall twice daily, morning and evening) of 4-9 (inclusive) is required. The patient is also required to complete at least 4 out of 5 morning and evening baseline NRS - Average Pain assessments Day –5 to Day –1 to be eligible.
5. Be able to understand and comply with the requirements of the study as judged by the investigator.
For inclusion in the genetic research, patients must fulfil the following criterion:
6. Provision of informed consent for genetic research. If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this CSP, so long as they consent.

E.4

Principal exclusion criteria

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
2. Previous enrolment or randomisation in the present study.
3. Participation in another clinical study with an IP during the last 30 days prior to enrolment.
4. Other pain that may confound assessment of neuropathic pain, as judged by the
investigator.
5. Central neuropathic pain conditions (caused by CNS injury/disease, eg, stroke, multiple sclerosis or spinal cord injury).
6. Any prior treatment of neuropathic pain with intrathecal pump or spinal cord stimulator.
7. History of treatment failure with ≥3 adequate trials of medications used to treat neuropathic pain, as judged by the investigator.
8. Use of any prohibited medication (see Table 4) at Visit 2.
9. History of any unstable medical disease (eg,, cardiovascular, renal insufficiency, hepatic insufficiency) which may interfere with the objectives of the study or with the safety of the subject, as judged by the investigator.
10. History of gastric ulcer or haemorrhage
11. History of significant psychiatric disease/disorder that could preclude reliable participation in the study, as judged by the investigator.
− Patients with a diagnosis of depression who are in remission for at least 12 weeks before enrolment with or without stable SSRI treatment are allowed in the study.
12. Patient with a cognitive disorder which could impair cooperation with study procedures, as judged by the investigator.
13. Clinically significant illness within 2 weeks before the administration of the IP as judged by the investigator.
14. Known malignancy within the past 5 years (with the exception of successfully treated basal cell carcinoma).
15. Malabsorption, gastrointestinal disorder or surgery leading to impaired drug absorption.
16. Donation of plasma from 2 weeks before Visit 1 (enrolment visit) or donation of blood from 3 months before Visit 1.
17. Abnormal vital signs, laboratory test value or ECG of clinical significance, as judged by the investigator.
− QTcF>450 ms or <340 ms, or a family history of long QT syndrome.
− Calculated Creatinine clearance ≤50 mL/min assessed by the Cockroft-Gault method.
− ALT or AST >1.5xULN
− Bilirubin > 1xULN
18. Positive Tuberculosis screening (i.e. chest x-ray and QuantiFERON® – TB Gold according to local requirements) as judged by investigator.
19. Immunisation with live vaccine within the previous 3 months, for other vaccines within the past 30 days.
20. History of latent, chronic, or recurrent infections (eg, tuberculosis, recurrent sinusitis, genital herpes, urinary tract infections) or at risk of infection (surgery,
trauma or significant infection, history of skin abscesses within 90 days prior to Visit 1).
21. Women with a positive pregnancy test on enrolment or before randomisation or lactating women.
22. History of alcohol or drug abuse within 2 years of entering the study.
23. Contraindication to ibuprofen/NSAIDs, such as ulcer and history of hypersensitivity reactions (eg, asthma, rhinitis or urticaria).
24. History of or positive test of human immunodeficiency virus (HIV) or hepatitis B or C.
25. Positive urine toxicology results for drugs of abuse including cannabis, cocaine, ecstacy, heroin/morphine, amphetamine and phenocyclidine (PCP). Visit 1 urine
toxicology results indicating opiate or other prescribed analgesic (including benzodiazepines) use in patients who had been receiving the medications for therapeutic reasons are permitted. However, patients who test positive for opiates or other excluded medications at Visit 2 (after the appropriate washout) are excluded.
In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
1. Previous allogeneic bone marrow transplant.
2. Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in mean NRS Average Pain Score

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline (Day –5 to Day –1) to Day 24 to Day 28.

E.5.2

Secondary end point(s)

1. Change from baseline in Numeric Rating Scale Pain Interference on Sleep and Activity score
2. To investigate the safety and tolerability of AZD2423

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Baseline (Day –5 to Day –1) to Day 24 to Day 28.
2. Weekly

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

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability and response rate

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.8.2.4

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

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

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

Russian Federation

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 last visit of the last patient undergoing the study.

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