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Trial registered on ANZCTR


Registration number
ACTRN12611001185954
Ethics application status
Not yet submitted
Date submitted
15/11/2011
Date registered
15/11/2011
Date last updated
27/02/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of EMA401 in the treatment of pain due to nerve injury.
Scientific title
A randomised, double-blind, placebo-controlled cross-over study of the efficacy and safety of the angiotensin II type 2 receptor antagonist EMA401 in patients with neuropathic pain following peripheral nerve injury.
Secondary ID [1] 273394 0
Protocol number EMA401-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral neuropathy due to nerve injury 279171 0
Condition category
Condition code
Neurological 279367 279367 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EMA401 100mg orally twice a day for 28 days

As this is a crossover design all patients will receive both EMA401 and placebo (in either order), with a 2 week washout period between each treatment
Intervention code [1] 283727 0
Treatment: Drugs
Comparator / control treatment
Placebo orally twice a day for 28 days

As this is a crossover design all patients will receive both EMA401 and placebo (in either order), with a 2 week washout period between each treatment
Control group
Placebo

Outcomes
Primary outcome [1] 285958 0
To determine the efficacy of 100 mg EMA401 orally twice daily for 28 days in reducing mean pain intensity score in patients with neuropathic pain due to peripheral nerve injury, compared to placebo.

This will be assessed using patient pain scores (on a scale of 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine).
Timepoint [1] 285958 0
After 28 days treatment
Secondary outcome [1] 294848 0
To evaluate the efficacy of 100 mg EMA401 orally twice daily for 28 days on psychophysical measures of sensitisation in pain pathways in patients with neuropathic pain due to peripheral nerve injury, compared to placebo.

This will be assessed by change in area of evoked pain from using brush, monofilaments, and thermal thresholds, patient pain scores, patient and clinician ratings of change, and patient questionnaires (specifically the Short Form McGill Pain Questionnaire, the Insomnia Severity Index, and the Brief Pain Inventory)
Timepoint [1] 294848 0
After 28 days treatment
Secondary outcome [2] 294849 0
To evaluate the potential efficacy of EMA401 using several alternate endpoints, including onset and maintenance of effect, responder rate, and time to 30% reduction in pain intensity
Timepoint [2] 294849 0
Over 28 days treatment
Secondary outcome [3] 294850 0
To evaluate the safety and tolerability of 100 mg EMA401 orally twice daily for 28 days in patients with neuropathic pain due to peripheral nerve injury.

This will be assessed by incidence and severity of adverse events, and changes and findings in laboratory parameters, physical and neurological examinations, vital signs, and ECG. All adverse events that occur will be measured by recording details of the event including description, start and stop dates, severity, seriousness, and relationship to study drug
Timepoint [3] 294850 0
After 28 days treatment

Eligibility
Key inclusion criteria
Patients who:
1. Are able to give voluntary written informed consent to participate in the study.

2. Are 18 to 80 years old inclusive.

3. Have had focal peripheral neuropathic pain for least 3 months prior to Screening that is related to nerve injury caused by trauma or surgery not associated with ongoing infection (examples include post-thoractomy syndrome, post-mastectomy syndrome, post-inguinal herniorrhaphy syndrome, post-radical neck dissection syndrome, traumatic neuropathies (bullet wounds, lacerations, road traffic accidents)).

4. Have a location of pain consistent with the area innervated by the affected nerve(s), with or without other sensory symptoms in the affected area.

5. Be diagnosed as suffering from moderate to severe pain across the Screening period. The assessment of moderate and severe pain will be made using an algorithm proprietary to Spinifex Pharmaceuticals. The investigator will be informed immediately as to whether the patient is eligible or ineligible on entering all the relevant pain scores in the electronic data capture portal.

6. Are female of non-child-bearing potential (i.e. either surgically sterilised or one year post-menopausal), or if of child-bearing potential, must have used adequate contraceptive precautions for 30 days prior to Screening, and must agree to use two approved methods of contraception for the duration of the study and for one month after administration of the last dose of study medication
OR
Are male and agree to use two approved methods of contraception for the duration of the study and until one month after administration of the last dose of the study medication.

7. Are able to read and understand the language of the scales and questionnaires used during the study.

8. Are contactable via telephone.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who:

1. Are pregnant or breast-feeding.

2. Do not and cannot comply with the protocol concomitant medication restrictions.

3. Have received an investigational drug within 30 days or 10 half-lives of the drug, whichever is longer, prior to the Screening visit.

4. Have previously received EMA401.

5. Are known to be allergic to EMA401 or any of the excipients.

6. Have a clinically significant history of systemic allergic disease (e.g., urticaria, atopic dermatitis).

7. Have a history of an allergic reaction to previous medication that required management by a health care professional.

8. Have non-peripheral nerve injury neuropathic pain component, or more than one cause or potential cause of pain symptoms.

9. Have deafferentation pain (spinal root avulsion injury, lumbo-sacral root pain).

10. Have intractable pain of unknown origin or active infection in the area of nerve injury.

11. Have had extensive surgery for the treatment of their nerve injury.

12. Have skin conditions in the affected area that in the investigator’s opinion could alter sensation.

13. Have any history of clinically significant cardiac arrhythmias or the presence of clinically significant abnormalities on electrocardiogram (ECG) at screening.

14. Have systolic blood pressure <100 or >150 mmHg, or a diastolic blood pressure < 50 or >90 mmHg on two consecutive measurements at least 10 minutes apart.

15. Have a resting pulse rate >100 or <50 beats per minute on two consecutive measurements at least 10 minutes apart.

16. Have a calculated creatinine clearance (using Cockroft and Gault formula) of less than 50 mL/min at Screening.

17. Have serum aspartate transaminase (AST), gamma glutamyl transaminase (GGT) or alanine transaminase (ALT) levels greater than 3.0 x the upper limit of normal or have total bilirubin concentrations greater than 2.0 x the upper limit of normal at Screening.

18. Have current hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV) infection.

19. Consume more than four units of alcohol daily for a man or three units of alcohol for a woman (one unit = 300 mL beer, one glass of wine, one measure of spirits) or have a history of alcohol abuse/dependence.

20. Other than the condition under study, have an active, uncontrolled medical condition, or psychiatric illness, or any other significant clinical disorder or laboratory finding that in the opinion of the investigator, precludes participation in the study or may interfere with the study objectives.

21. Other than the condition under study, have had a clinically significant illness or operative procedure within 4 weeks of the Screening visit.

22. Are known to be poor compliers or those unlikely to attend study visits.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final

Funding & Sponsors
Funding source category [1] 284208 0
Commercial sector/Industry
Name [1] 284208 0
Spinifex Pharmaceuticals Pty Ltd
Address [1] 284208 0
Level 1, 122 Toorak Rd
South Yarra VIC 3141
Country [1] 284208 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Spinifex Pharmaceuticals Pty Ltd
Address
Level 1, 122 Toorak Rd
South Yarra VIC 3141
Country
Australia
Secondary sponsor category [1] 269165 0
None
Name [1] 269165 0
Address [1] 269165 0
Country [1] 269165 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 286170 0
Ethics committee address [1] 286170 0
Ethics committee country [1] 286170 0
Date submitted for ethics approval [1] 286170 0
30/11/2012
Approval date [1] 286170 0
Ethics approval number [1] 286170 0

Summary
Brief summary
Peripheral neuropathy is caused by damage to nerves. Current therapy needs to be improved as a significant proportion of neuropathic pain patients don’t respond to current therapy and these treatments have dose-limiting side effects.

EMA401 is an angiotensin II type 2 (AT2) receptor antagonist, a class of molecules that offers an innovative approach to the treatment of neuropathic pain. EMA401 has shown efficacy in a number of relevant models and good human safety and pharmacokinetics in Phase 1 studies.

This study will look at whether EMA401 reduces pain in patients who have peripheral neuropathy caused by nerve damage, and whether it is well tolerated.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33394 0
Address 33394 0
Country 33394 0
Phone 33394 0
Fax 33394 0
Email 33394 0
Contact person for public queries
Name 16641 0
Tom McCarthy
Address 16641 0
Level 1, 122 Toorak Rd
South Yarra VIC 3141
Country 16641 0
Australia
Phone 16641 0
+61 3 9938 1205
Fax 16641 0
Email 16641 0
tom.mccarthy@spinifexpharma.com.au
Contact person for scientific queries
Name 7569 0
Tom McCarthy
Address 7569 0
Level 1, 122 Toorak Rd
South Yarra VIC 3141
Country 7569 0
Australia
Phone 7569 0
+61 3 9938 1205
Fax 7569 0
Email 7569 0
tom.mccarthy@spinifexpharma.com.au

No data has been provided for results reporting
Summary results
Not applicable