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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03094195




Registration number
NCT03094195
Ethics application status
Date submitted
23/03/2017
Date registered
29/03/2017
Date last updated
8/10/2021

Titles & IDs
Public title
Dose Response Study of EMA401 in Patients With Post-herpetic Neuralgia (PHN)
Scientific title
A Double-blind, Placebo-controlled, Randomized Dose Ranging Trial to Determine the Safety and Efficacy of Three Dose Levels of EMA401 in Reducing 24-hour Average Pain Intensity Score in Patients With Post-herpetic Neuralgia
Secondary ID [1] 0 0
CEMA401A2201
Universal Trial Number (UTN)
Trial acronym
EMPHENE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-herpetic Neuralgia 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EMA401
Treatment: Drugs - Placebo

Experimental: EMA401 25mg BID - Ema401 25 mg was administered orally twice a day

Experimental: EMA401 100mg BID - Ema401 100 mg was administered orally twice a day

Placebo comparator: Placebo BID - Matching placebo capsules administered orally twice a day


Treatment: Drugs: EMA401
EMA401

Treatment: Drugs: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-response in Change in Weekly Mean of the 24-hour Average Pain Score, Using an 11-point Numeric Rating Scale (NRS), From Baseline to Week 12
Assessment method [1] 0 0
Since the 300 mg b.i.d. dose of EMA401 could not be initiated in the study due to premature study termination, the dose-response characterization was not performed. Specifically, only the trend test deduced from the set of candidate models was performed but the dose response estimation was not conducted.
Timepoint [1] 0 0
Baseline up to Week 12
Secondary outcome [1] 0 0
Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12
Assessment method [1] 0 0
The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. The following parameters were evaluated using the 11-point NRS: 24-hour Average Pain Score and 24-hour Worst Pain Score Patients evaluated their "average pain" and "worst pain" during the past 24 hours in the evening prior to sleep by touching the appropriate corresponding number between zero and ten on a eDiary device.
Timepoint [1] 0 0
Baseline up to Week 12
Secondary outcome [2] 0 0
Change in Brief Pain Inventory-Short Form Interference (BPI-SF) Mean Total Score From Baseline to Week 12
Assessment method [2] 0 0
The BPI-SF is a validated, self-administered (at clinic) questionnaire that assesses pain severity and its mpact on daily functions. Patients were asked to complete the 7-item pain interference scale that assessed the degree to which pain interfered with walking and other physical activity, work, mood, relations with others and sleep using a zero to ten numeric rating scale (NRS) with zero being "does not interfere" and ten being "completely interferes". A reduction in mean indicates improvement
Timepoint [2] 0 0
Baseline up to Week 12
Secondary outcome [3] 0 0
Change in Weekly Mean of the 24-hour Worst Pain Score, Using an 11-point NRS, From Baseline to Week 12
Assessment method [3] 0 0
The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. The following parameters were evaluated using the 11-point NRS: 24-hour Average Pain Score and 24-hour Worst Pain Score Patients evaluated their "average pain" and "worst pain" during the past 24 hours in the evening prior to sleep by touching the appropriate corresponding number between zero and ten on a eDiary device.
Timepoint [3] 0 0
Baseline up to Week 12
Secondary outcome [4] 0 0
Number of Participants Per Patient Global Impression of Change Category at Week 12
Assessment method [4] 0 0
The Patient Global Impression of Change (PGIC) is a patient-reported instrument that measures change in overall status on a scale ranging from one ("very much improved") to seven ("very much worse"). The PGIC is based on the validated Clinical Global Impression of Change scale. The PGIC was to be completed by patients using the electronic tablet at the site
Timepoint [4] 0 0
Baseline up to Week 12
Secondary outcome [5] 0 0
Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale
Assessment method [5] 0 0
The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. The number of patients with observed response, i.e. a decrease of 30% /50% units in weekly mean of the 24-hour average pain score NRS. Logistic regression model with region, treatment, sex, use of PHN medications (yes/no) as factors and age and baseline NRS as covariates. An odds ratio \>1 = higher chance of a clinically important improvement.
Timepoint [5] 0 0
Baseline up to Week 12
Secondary outcome [6] 0 0
Percentage of Patients Achieving at Least 50% Pain Reduction at Week 12 on NRS 11 Point Scale
Assessment method [6] 0 0
The NRS is an 11-point scale ranging from zero ("no pain") to ten ("pain as bad as you can imagine") for self-reporting of pain by patients. The number of patients with observed response, i.e. a decrease of 50% units in weekly mean of the 24-hour average pain score NRS. Logistic regression model with region, treatment, sex, use of PHN medications (yes/no) as factors and age and baseline NRS as covariates. An odds ratio \>1 = higher chance of a clinically important improvement.
Timepoint [6] 0 0
Baseline up to Week 12
Secondary outcome [7] 0 0
Mean Change in Insomnia Severity Index (ISI) From Baseline to Week 12
Assessment method [7] 0 0
Patients were asked to complete the ISI using five-point Likert-style scale as a measure of perceived sleep difficulties. Scores ranged from zero to 28, with a cut-off score of eight suggesting the presence of sub-threshold insomnia. The questionnaire assessed the severity of insomnia, satisfaction with current sleep pattern, sleep interference, "noticeability" of sleeping problem to others and concern about sleeping problems.
Timepoint [7] 0 0
Baseline up to Week 12
Secondary outcome [8] 0 0
Change in Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 12
Assessment method [8] 0 0
The Neuropathic Pain Symptom Inventory (NPSI) is a 12 item patient reported outcome measure that contains 10 descriptors representing 5 dimensions of pain (burning pain, deep/pressing pain, paroxysmal pain, evoked pain and paraesthesia/dysesthesia) and 2 temporal items designed to assess pain duration and the number of pain paroxysms. The sum of the responses to the 10 questions (all except temporal questions) was regarded as the total score and was divided by 10 (10 questions). The range of the total score and of the 5 dimensional scores is 0 to 10. Lower values represent better outcomes.
Timepoint [8] 0 0
Baseline up to Week 12
Secondary outcome [9] 0 0
Plasma Pharmacokinetics (PK) Concentrations at Week 8 and 12
Assessment method [9] 0 0
Due to the premature termination of the study, the number of patients and observations providing PK data was much smaller than planned, and no PK model was developed. As a consequence, no PK parameters (Cmax, Tmax, AUC) were derived for this study. Only, summary statistics of the plasma concentrations were calculated
Timepoint [9] 0 0
Week 8, Week 12
Secondary outcome [10] 0 0
Exposure-response (Decrease in Pain Intensity) Via Evaluation of Effect of EMA401 Exposure on Efficacy Variables (e.g. Change From Baseline of Pain Score), Via Descriptive Pharmacokinetics/ Pharmacodynamics (PK/PD)
Assessment method [10] 0 0
Due to the premature termination of the study, the number of patients providing data for PKPD analysis data was much smaller than planned and no model to correlate drug exposure (PK) with the change in the pain score (PD) was developed
Timepoint [10] 0 0
Baseline, Week 8, Week 12
Secondary outcome [11] 0 0
Treatment Emergent Adverse Events During Urgent Safety Measure (USM) Follow-Up
Assessment method [11] 0 0
Participants were instructed to stop taking drug immediately upon termination of study and asked to come in for two unscheduled visits for follow up safety assessments
Timepoint [11] 0 0
Approximately from 3 weeks after end of study up to 16 weeks

Eligibility
Key inclusion criteria
* At the time of Screening, must have had documented diagnosis of PHN (ICD-10 code B02.29), defined as pain in the region of the rash persisting for more than 6 months after onset of herpes zoster rash.
* Assessed as suffering from moderate to severe neuropathic pain across the Screening epoch (NRS = 4).
* Patients must have had documented past and/or ongoing inadequate treatment response (having insufficient pain relief with treatment or inability to tolerate) to at least 2 different prescribed therapies commonly used to treat and considered effective by the Investigator for the treatment of PHN.
* Patient must have been willing to complete daily eDiary
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History or had current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study
* Had a major depressive episode within 6 months prior to Screening and/or a history of diagnosed recurrent major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) diagnostic criteria
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
* Had evidence of significant renal insufficiency or pre-existing liver condition
* Had platelets = 100 x 10^9/L, or neutrophil count < 1.2 x 10^9/L (or equivalent), hemoglobin = 100 g/L for women or hemoglobin = 110 g/L for men.
* Patients who had a known diagnosis of diabetes and are stable on medication with a hemoglobin A1c > 8%. Those who did not have a known diagnosis of diabetes with a hemoglobin A1c > 7%.

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?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/03/2019
Sample size
Target
Accrual to date
Final
130
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Klagenfurt
Country [2] 0 0
Austria
State/province [2] 0 0
Vienna
Country [3] 0 0
Belgium
State/province [3] 0 0
Pellenberg
Country [4] 0 0
Canada
State/province [4] 0 0
CAN
Country [5] 0 0
Canada
State/province [5] 0 0
Quebec
Country [6] 0 0
Czechia
State/province [6] 0 0
Brno
Country [7] 0 0
Czechia
State/province [7] 0 0
Chocen
Country [8] 0 0
Czechia
State/province [8] 0 0
Plzen-Bory
Country [9] 0 0
Czechia
State/province [9] 0 0
Praha 10
Country [10] 0 0
Denmark
State/province [10] 0 0
Odense C
Country [11] 0 0
France
State/province [11] 0 0
Boulogne Billancourt
Country [12] 0 0
France
State/province [12] 0 0
Clermont-Ferrand
Country [13] 0 0
France
State/province [13] 0 0
LILLE Cédex
Country [14] 0 0
France
State/province [14] 0 0
Nice
Country [15] 0 0
Germany
State/province [15] 0 0
Nordrhein Westfalen
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Germany
State/province [17] 0 0
Dresden
Country [18] 0 0
Germany
State/province [18] 0 0
Erlangen
Country [19] 0 0
Germany
State/province [19] 0 0
Haar
Country [20] 0 0
Germany
State/province [20] 0 0
Kiel
Country [21] 0 0
Germany
State/province [21] 0 0
Leipzig
Country [22] 0 0
Germany
State/province [22] 0 0
Wiesbaden
Country [23] 0 0
Hungary
State/province [23] 0 0
HUN
Country [24] 0 0
Hungary
State/province [24] 0 0
Kistarcsa
Country [25] 0 0
Hungary
State/province [25] 0 0
Szeged
Country [26] 0 0
Italy
State/province [26] 0 0
Rome
Country [27] 0 0
Japan
State/province [27] 0 0
Hyogo
Country [28] 0 0
Japan
State/province [28] 0 0
Kanagawa
Country [29] 0 0
Japan
State/province [29] 0 0
Osaka
Country [30] 0 0
Japan
State/province [30] 0 0
Saitama
Country [31] 0 0
Japan
State/province [31] 0 0
Shizuoka
Country [32] 0 0
Japan
State/province [32] 0 0
Tokyo
Country [33] 0 0
Japan
State/province [33] 0 0
Oita
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Gyeonggi-do
Country [35] 0 0
Norway
State/province [35] 0 0
Oslo
Country [36] 0 0
Poland
State/province [36] 0 0
Olsztyn
Country [37] 0 0
Poland
State/province [37] 0 0
Warszawa
Country [38] 0 0
Portugal
State/province [38] 0 0
Almada
Country [39] 0 0
Portugal
State/province [39] 0 0
Aveiro
Country [40] 0 0
Portugal
State/province [40] 0 0
Leiria
Country [41] 0 0
Portugal
State/province [41] 0 0
Lisboa
Country [42] 0 0
Portugal
State/province [42] 0 0
Porto
Country [43] 0 0
Slovakia
State/province [43] 0 0
SVK
Country [44] 0 0
Slovakia
State/province [44] 0 0
Banska Bystrica
Country [45] 0 0
Slovakia
State/province [45] 0 0
Presov
Country [46] 0 0
Slovakia
State/province [46] 0 0
Spisska Nova Ves
Country [47] 0 0
Spain
State/province [47] 0 0
Barcelona
Country [48] 0 0
Taiwan
State/province [48] 0 0
Tainan
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Durham
Country [50] 0 0
United Kingdom
State/province [50] 0 0
GBR
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Liverpool

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03094195