Clinical Trials Register

Summary
EudraCT Number:	2011-000977-29
Sponsor's Protocol Code Number:	EMA401-003
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-04-27
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

Czechia - SUKL

A.2

EudraCT number

2011-000977-29

A.3

Full title of the trial

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

A.3.1

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

A study of oral EMA401 in the treatment of pain following shingles to see if EMA401 can reduce the level of pain.

A.4.1

Sponsor's protocol code number

EMA401-003

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	Spinifex Pharmaceuticals Pty 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	Spinifex Pharmaceuticals Pty 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	Spinifex Pharmaceuticals Pty Ltd
B.5.2	Functional name of contact point	Information Desk
B.5.3	Address:
B.5.3.1	Street Address	South Yarra Corporate Centre, Suite T18, Level 1, 122 Toorak Road
B.5.3.2	Town/ city	SOUTH YARRA
B.5.3.3	Post code	VIC 3141
B.5.3.4	Country	Australia
B.5.4	Telephone number	+61 3 9938 1205
B.5.5	Fax number	+613 9820 8262
B.5.6	E-mail	info@spinifexpharma.com.au

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	EMA401 Sodium Salt
D.3.2	Product code	EMA401
D.3.4	Pharmaceutical form	Capsule, hard
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	EMA401
D.3.9.3	Other descriptive name	sodium salt of the parent carboxylic acid which is an angiotensin II type 2 (AT2) receptor antagonist
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	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	Capsule, hard
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

postherpetic neuralgia

E.1.1.1

Medical condition in easily understood language

pain following shingles

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	PT
E.1.2	Classification code	10036376
E.1.2	Term	Post herpetic neuralgia
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 determine the efficacy of EMA401 when administered orally, twice daily (100 mg b.i.d.), in patients with postherpetic neuralgia, as assessed by difference in mean pain intensity score compared to placebo.

E.2.2

Secondary objectives of the trial

1. To evaluate the potential efficacy of EMA401 using several alternate endpoints (see efficacy parameters)
2. To evaluate the safety and tolerability of EMA401 in patients with postherpetic neuralgia
3. To evaluate the pharmacokinetics of EMA401 in patients with postherpetic neuralgia

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Be able to give voluntary written informed consent to participate in the study.
2.Be over 18 years of age.
3.Be diagnosed as suffering from PHN defined as pain persisting for more than six months after onset of herpes zoster rash.
4.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.
5.Willing and be able to comply with all study procedures.
6.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.
7.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: Agrees 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.
Approved methods of contraception include:
•Surgical sterilization (vasectomy at least six 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 (IUD), contraceptive hormonal patches, implants or injections by female patients or female partners of male patients
8.Be fluent in the language of the endpoint scales provided to patients in the study.

E.4

Principal exclusion criteria

1.Be currently receiving any of the prohibited medications listed below and in Section 7.7.2 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 PHN. Patients may be enrolled if stable on therapy for their PHN as specified in the permitted medications with restrictions below and in Section 7.7.1
2.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.
3.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.
4.Have a clinically significant history of systemic allergic disease (e.g., urticaria, atopic dermatitis).
5.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).
6.Have a pulse rate, after sitting for at least 5 minutes, greater than 100 beats per minute (bpm) or lower than 50 bpm, or 45 bpm if on beta blockers, on two consecutive measurements (at least 10 minutes apart and completed within 20 minutes of the initial measurement).
7.Known to be diabetic.
8.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 has a history of alcohol abuse/dependence.
9.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).
10.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 (Visit 1).
11.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.
12.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).
13. Have undergone neurolytic or neurosurgical therapy for postherpetic neuralgia.
14.Have other moderate to severe pain condition that may confound the self-evaluation of pain due to postherpetic neuralgia.
15.Have skin conditions in the affected area that in the investigator’s opinion could alter sensation.
16.Have active herpes zoster upon physical examination at Screening (Visit 1) or during the study.
17.Have hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV) infection as defined by being seropositive for hepatitis B surface antigen (HBsAg), HCV antibodies or HIV antibodies respectively.
18.Have a history of at least one genital herpes outbreak.
19.Are pregnant or lactating.

E.5 End points

E.5.1

Primary end point(s)

Efficacy: Change in mean pain intensity score (using the 11-point numerical rating scale/Likert scale) between baseline and the last week of dosing (Day 22 to 28).

E.5.1.1

Timepoint(s) of evaluation of this end point

A patient's daily pain intensity score across the preceding 24 hours will be recorded at a single timepoint in the evening prior to sleep. The daily pain intensity score will be used to calculate the mean pain intensity score at both baseline (consists of daily pain scores recorded over 7 consecutive days during the Screening Period) and across the last week (Day 22 to 28) of the Treatment Period.

E.5.2

Secondary end point(s)

Secondary efficacy endpoints:
1.Onset and maintenance of effect as defined by pattern of change in the mean pain intensity score over the entire Treatment Period.
2.Proportion of patients achieving a ≥30% reduction in mean pain intensity score compared to baseline (i.e. responder rate).
Tertiary efficacy endpoints:
1.Time to 30% decrease from baseline in mean pain intensity score
2.Quality of Life assessed by the 7-Item Pain Interference aspect of the Brief Pain Inventory (BPI) and the complete Insomnia Severity Index (ISI) [at baseline (Day 1) and Day 28]
3.Patient ratings assessed by Patient Global Impression of Change Scale (PGIC) [at Day 28]
4.Description of some of the qualities of patients’ pain (e.g. throbbing, gnawing shooting) assessed by the modified version of the Short-Form McGill Pain Questionnaire (SF-MPQ-2) [at baseline (Day 1) and Day 28]
5.Emotional and Psychological Functioning assessed by Depression Anxiety Positive Outlook Scale (DAPOS) and Pain Catastrophising Scale (PCS) [at baseline (Day 1) and Day 28]

E.5.2.1

Timepoint(s) of evaluation of this end point

Over the entire Treatment Period.

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

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

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

Bulgaria

Czech Republic

Serbia

South Africa

Ukraine

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

LVLS

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