Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000822987
Ethics application status
Approved
Date submitted
4/08/2011
Date registered
4/08/2011
Date last updated
4/08/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of oral EMA401 in the treatment of pain following shingles to see if EMA401 can reduce the level of pain.
Scientific title
A double-blind, placebo-controlled, randomised trial to prove the therapeutic concept and to determine the safety, tolerability and pharmacokinetic profile of EMA401 (angiotensin II type 2 receptor antagonist) administered orally in patients with postherpetic neuralgia.
Secondary ID [1] 262632 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postherpetic Neuralgia 268333 0
Condition category
Condition code
Neurological 268468 268468 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EMA401 sodium salt capsules (2 x 50 mg) will be administered at a dose of 100 mg twice daily, taken on an empty stomach at least 1 hour before a meal (total 200 mg daily dose).

The two capsules on each dosing occasion should be taken orally with a minimum of 200 mL of water. The Treatment Period will be 29 days consisting of 28 days of twice daily dosing and a single dose on the morning of Day 29, to give a total of 57 doses, followed by 13 days (+/- 3 days) without treatment.
Intervention code [1] 266980 0
Treatment: Drugs
Comparator / control treatment
Patients will be randomised in a 1:1 ratio to receive EMA401 or placebo.

Placebo capsules, identical to the active drug in appearance and contain the same excipients but not containing EMA401 sodium salt.

Two Placebo capsules will be administered twice daily, taken on an empty stomach at least 1 hour before a meal. The two capsules on each dosing occasion should be taken orally with a minimum of 200 mL of water.

The Treatment Period will be 29 days consisting of 28 days of twice daily dosing and a single dose on the morning of Day 29, to give a total of 57 doses, followed by 13 days (+/- 3 days) without treatment.
Control group
Placebo

Outcomes
Primary outcome [1] 269218 0
Change in mean pain intensity score (using an 11-point numerical rating scale/Likert scale) between baseline and the last week of dosing (Day 22 to 28).
Timepoint [1] 269218 0
At Baseline (consists of daily pain scores recorded over 7 consecutive days during the Screening Period (week 0)) and at week 4 from intervention commencement.

The daily pain intensity score is averaged over 7 days to obtain the mean pain intensity score for a week.
Secondary outcome [1] 279141 0
Onset and maintenance of effect as defined by pattern of change in the mean pain intensity score over the entire Treatment Period.
Timepoint [1] 279141 0
At Baseline (week 0) and at 1 week, 2 weeks, 3 weeks and 4 weeks after intervention commencement.
Secondary outcome [2] 279142 0
Proportion of patients achieving a greater than or equal to 30% reduction in mean pain intensity score compared to baseline
Timepoint [2] 279142 0
At Baseline (week 0) and at week 4 from intervention commencement.

Eligibility
Key inclusion criteria
Patients will be entered into this study only if they meet all of the following criteria;
be able to give voluntary written informed consent to participate in the study;
be over eighteen years of age;
be diagnosed as suffering from post herpetic neuralgia defined as pain persisting for more than six months after onset of herpes zoster rash;
be diagnosed as suffering from moderate to severe pain across the Screening Period;
willing and be able to comply with all study procedures;
for females, have a negative pregnancy test at the Screening Visit (Visit 1) and at Visit 2 (Day 1) prior to administration of study medication;
for females, be 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;
for males, agree to use two approved methods of contraception for the duration of the study and until 1 month after administration of the last dose of the study medication, where approved methods of contraception include surgical sterilization (vasectomy at least 6 months prior to dosing), condom use by male partners of female patients or by male patients, birth control pills, diaphragm with vaginal spermicide, intra uterine device, contraceptive hormonal patches, implants or injections by female patients or female partners of male patients;
and be fluent in the language of the endpoint scales provided to patients in the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who meet any of the following criteria will be excluded from participating in the study;
be currently receiving any of the listed prohibited medications or have received within 30 days prior to the Screening Visit (Visit 1) or is anticipated to receive after the start of the trial (i.e. on or after Visit 1) any new prescription systemic or topical medication for their post herpetic neuralgia, patients may be enrolled if stable on therapy for their post herpetic neuralgia as specified in the list of permitted medications;
have received an investigational drug within 30 days or 10 half-lives of the drug, whichever is longer, prior to the Screening Visit (Visit 1) or have previously received EMA401; known to be allergic to EMA401 or any of the excipients or who have a history of an allergic reaction to previous medication that required management by a health care professional;
have a clinically significant history of systemic allergic disease (e.g., urticaria, atopic dermatitis);
have a blood pressure, after resting for at least 5 minutes, outside a systolic blood pressure range of 100-150 mmHg or a diastolic blood pressure outside a range of 50-90 mmHg on two consecutive measurements (at least 10 minutes apart and completed within 20 minutes of the initial measurement);
have a pulse rate, after sitting for at least 5 minutes, greater than 100 beats per minute or lower than 50 beats per minute, or 45 beats per minute if on beta blockers, on two consecutive measurements (at least 10 minutes apart and completed within 20 minutes of the initial measurement);
known to be diabetic;
consume more than 4 units of alcohol daily for a man or 3 units of alcohol for a woman (1 unit equals 300 mL beer, one glass of wine, one measure of spirits) or has a history of alcohol abuse/dependence;
have evidence of significant renal insufficiency, indicated by an estimated creatinine clearance using the Cockcroft-Gault formula of less than 50 mL/min at Screening (Visit 1);
have serum aspartate transaminase, gamma glutamyl transaminase or alanine transaminase levels greater than 3 times the upper limit of normal or have total bilirubin concentrations greater than 2 times the upper limit of normal at Screening (Visit 1);
other than pain as a result of postherpetic neuralgia, have an active, uncontrolled medical condition (e.g., neurological, gastrointestinal, renal, hepatic, cardiovascular, pulmonary, metabolic, endocrine, haematological, genitourinary or other major disorder), or psychiatric illness (e.g., depression, schizophrenia), 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;
other than pain as a result of postherpetic neuralgia, have had a clinically significant illness or operative procedure within 4 weeks of the Screening Visit (Visit 1) (e.g. influenza, myocardial infarction);
have undergone neurolytic or neurosurgical therapy for postherpetic neuralgia;
have other moderate to severe pain condition that may confound the self-evaluation of pain due to postherpetic neuralgia;
have skin conditions in the affected area that in the investigator's opinion could alter sensation;
have active herpes zoster upon physical examination at Screening (Visit 1) or during the study;
have hepatitis B, hepatitis C or human immunodeficiency virus infection as defined by being seropositive for hepatitis B surface antigen, hepatitis C virus antibodies or human immunodeficiency virus antibodies respectively;
have a history of at least one genital herpes outbreak;
or are pregnant or lactating.

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
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/08/2011
Actual
10/08/2011
Date of last participant enrolment
Anticipated
Actual
18/05/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
172
Accrual to date
Final
183
Recruitment outside Australia
Country [1] 3724 0
South Africa
State/province [1] 3724 0
Country [2] 3725 0
Bulgaria
State/province [2] 3725 0
Country [3] 3726 0
Czech Republic
State/province [3] 3726 0
Country [4] 3727 0
Serbia and Montenegro
State/province [4] 3727 0
Country [5] 3728 0
Ukraine
State/province [5] 3728 0
Country [6] 3729 0
Georgia
State/province [6] 3729 0

Funding & Sponsors
Funding source category [1] 267454 0
Commercial sector/Industry
Name [1] 267454 0
Spinifex Pharmaceuticals Pty Ltd
Country [1] 267454 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Spinifex Pharmaceuticals Pty Ltd
Address
Corporate One, Suite G5, 84 Hotham St, Preston, VIC, 3072, Australia
Country
Australia
Secondary sponsor category [1] 266499 0
None
Name [1] 266499 0
Address [1] 266499 0
Country [1] 266499 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269420 0
Pharma-Ethics Pty Ltd
Ethics committee address [1] 269420 0
Ethics committee country [1] 269420 0
South Africa
Date submitted for ethics approval [1] 269420 0
08/04/2011
Approval date [1] 269420 0
26/05/2011
Ethics approval number [1] 269420 0
11054264
Ethics committee name [2] 269421 0
Zvezdara University Medical Center
Ethics committee address [2] 269421 0
Ethics committee country [2] 269421 0
Serbia and Montenegro
Date submitted for ethics approval [2] 269421 0
14/04/2011
Approval date [2] 269421 0
20/04/2011
Ethics approval number [2] 269421 0
Ethics committee name [3] 269422 0
Clinical Centre of Vojvodine
Ethics committee address [3] 269422 0
Ethics committee country [3] 269422 0
Serbia and Montenegro
Date submitted for ethics approval [3] 269422 0
15/04/2011
Approval date [3] 269422 0
05/05/2011
Ethics approval number [3] 269422 0
00-01/256
Ethics committee name [4] 269423 0
Ethics Committee The University Hospital and the Faculty Medicine Palacky University in Olomouc
Ethics committee address [4] 269423 0
Ethics committee country [4] 269423 0
Czech Republic
Date submitted for ethics approval [4] 269423 0
26/04/2011
Approval date [4] 269423 0
16/05/2011
Ethics approval number [4] 269423 0
62/11
Ethics committee name [5] 269424 0
Ethics Committee of the Institute for Clinical and Experimental Medicine and Faculty Thomayer Hospital
Ethics committee address [5] 269424 0
Ethics committee country [5] 269424 0
Czech Republic
Date submitted for ethics approval [5] 269424 0
19/04/2011
Approval date [5] 269424 0
11/05/2011
Ethics approval number [5] 269424 0
745/11 (L 11-32)
Ethics committee name [6] 269425 0
The University Hospital Kralovske Vinohrady
Ethics committee address [6] 269425 0
Ethics committee country [6] 269425 0
Czech Republic
Date submitted for ethics approval [6] 269425 0
26/04/2011
Approval date [6] 269425 0
04/05/2011
Ethics approval number [6] 269425 0
KH/17/0/2011
Ethics committee name [7] 269426 0
Ethics Committee, Faculty Hospital Hradec Kralove
Ethics committee address [7] 269426 0
Ethics committee country [7] 269426 0
Czech Republic
Date submitted for ethics approval [7] 269426 0
19/04/2011
Approval date [7] 269426 0
09/06/2011
Ethics approval number [7] 269426 0
201106 D04M
Ethics committee name [8] 269427 0
Faculty Hospital u sv. Anny v Brne Vystavni
Ethics committee address [8] 269427 0
Ethics committee country [8] 269427 0
Czech Republic
Date submitted for ethics approval [8] 269427 0
20/04/2011
Approval date [8] 269427 0
08/06/2011
Ethics approval number [8] 269427 0
30L/2011
Ethics committee name [9] 269497 0
Clinical Centre of Serbia Ethics Committee
Ethics committee address [9] 269497 0
Ethics committee country [9] 269497 0
Serbia and Montenegro
Date submitted for ethics approval [9] 269497 0
17/05/2011
Approval date [9] 269497 0
09/06/2011
Ethics approval number [9] 269497 0
1009/24-A and 1009/24-B
Ethics committee name [10] 269498 0
Central Ethics Committee of the Health Ministry of Ukraine
Ethics committee address [10] 269498 0
Ethics committee country [10] 269498 0
Ukraine
Date submitted for ethics approval [10] 269498 0
28/04/2011
Approval date [10] 269498 0
14/06/2011
Ethics approval number [10] 269498 0
5.12-680/KE

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32880 0
Dr Milton Raff
Address 32880 0
Christiaan Barnard Memorial Hospital
181 Longmarket Street
Cape Town, 8000
South Africa
Country 32880 0
South Africa
Phone 32880 0
+21 4806252
Fax 32880 0
Email 32880 0
[email protected]
Contact person for public queries
Name 16127 0
Tom McCarthy
Address 16127 0
Spinifex Pharmaceuticals Pty Ltd
Corporate One, Suite G5, 84 Hotham St
Preston, VIC, 3072, Australia
Country 16127 0
Australia
Phone 16127 0
+61 3 9863 6820
Fax 16127 0
Email 16127 0
[email protected]
Contact person for scientific queries
Name 7055 0
Geoff Kitson
Address 7055 0
10, The Courtyard
East Park, Crawley
West Sussex RH10 6AG
Country 7055 0
United Kingdom
Phone 7055 0
+44 1293 425300
Fax 7055 0
+44 1293 415893
Email 7055 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseFuture drug discovery in renin-angiotensin-aldosterone system intervention.2017https://dx.doi.org/10.1080/17460441.2017.1335301
EmbaseThe Angiotensin AT2 Receptor: Froma Binding Site to a Novel Therapeutic Target.2022https://dx.doi.org/10.1124/pharmrev.120.000281
N.B. These documents automatically identified may not have been verified by the study sponsor.