Dose Response Study of EMA401 in Patients With Post-herpe... | NCT03094195 | Trialant
NCT03094195
Sponsor
Novartis Pharmaceuticals
Status
Terminated
Last Update Posted
Oct 8, 2021Actual
Enrollment
130Actual
Phase
Phase 2
Conditions
Post-herpetic Neuralgia
Interventions
EMA401
Placebo
Countries
Australia
Austria
Belgium
Canada
Czechia
Denmark
France
Germany
Hungary
Italy
Japan
Norway
Poland
Portugal
Slovakia
South Korea
Spain
Taiwan
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03094195
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CEMA401A2201
Secondary IDs
Not provided
Brief Title
Dose Response Study of EMA401 in Patients With Post-herpetic Neuralgia (PHN)
Official 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
Acronym
EMPHENE
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Oct 2021
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
The study was terminated early due to pre-clinical toxicity data that became available after start of trial
Expanded Access Info
No
Start Date
Jun 27, 2017Actual
Primary Completion Date
Mar 7, 2019Actual
Completion Date
Mar 7, 2019Actual
First Submitted Date
Mar 23, 2017
First Submission Date that Met QC Criteria
Mar 23, 2017
First Posted Date
Mar 29, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Mar 6, 2020
Results First Submitted that Met QC Criteria
May 2, 2020
Results First Posted Date
May 14, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 7, 2021
Last Update Posted Date
Oct 8, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study was designed to characterize dose response, and evaluate safety and efficacy of three different doses of EMA401 compared to placebo in patients with post-herpetic neuralgia (PHN).
Detailed Description
This was an interventional, randomized, parallel, placebo-controlled, dose ranging, double-blind treatment study consisting of 3 periods i.e. Screening, Treatment, and Treatment withdrawal. The study was planned in two cohorts. The initial cohort had three treatment arms i.e. Placebo b.i.d., EMA401 25 mg b.i.d., or EMA401 100 mg b.i.d. Following an unblinded safety review by an independent DMC, the second cohort was to have been initiated with an additional treatment arm i.e. EMA401 300 mg b.i.d.. Due to the premature study termination, the second cohort was not initiated. At the end of treatment period the 25mg BID and 100mg BID arms were re-randomized (1:1) to the same treatment or placebo. Placebo arm stayed on placebo. The planned duration of treatment period was 12 weeks and 1 week of treatment withdrawal at the end of treatment period. The study was terminated early due to pre-clinical toxicity data that became available after start of trial. Novartis implemented a Urgent Safety Measure (USM) which instructed sites to discontinue study treatment immediately and to have all patients return for additional laboratory assessments (full hematology including coagulation and clinical chemistry panel). Safety data from the USM was presented as a separate outcome measure table and not included in the Adverse Event section.
Conditions Module
Conditions
Post-herpetic Neuralgia
Keywords
post-herpetic neuralgia
neuropathic pain
angiotensin II type 2 receptor antagonist
dose ranging
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
130Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
EMA401 25mg BID
Experimental
Ema401 25 mg was administered orally twice a day
Drug: EMA401
EMA401 100mg BID
Experimental
Ema401 100 mg was administered orally twice a day
Drug: EMA401
Placebo BID
Placebo Comparator
Matching placebo capsules administered orally twice a day
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
EMA401
Drug
EMA401
EMA401 100mg BID
EMA401 25mg BID
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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
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.
Baseline up to Week 12
Secondary Outcomes
Measure
Description
Time Frame
Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
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%.
Rice ASC, Dworkin RH, Finnerup NB, Attal N, Anand P, Freeman R, Piaia A, Callegari F, Doerr C, Mondal S, Narayanan N, Ecochard L, Flossbach Y, Pandhi S. Efficacy and safety of EMA401 in peripheral neuropathic pain: results of 2 randomised, double-blind, phase 2 studies in patients with postherpetic neuralgia and painful diabetic neuropathy. Pain. 2021 Oct 1;162(10):2578-2589. doi: 10.1097/j.pain.0000000000002252.
See Also Links
Label
URL
A Plain Language Trial Summary is available on novartisclinicaltrials.com
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
Change in Brief Pain Inventory-Short Form Interference (BPI-SF) Mean Total Score From Baseline to Week 12
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
Baseline up to Week 12
Change in Weekly Mean of the 24-hour Worst Pain Score, Using an 11-point NRS, From Baseline to Week 12
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.
Baseline up to Week 12
Number of Participants Per Patient Global Impression of Change Category at Week 12
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
Baseline up to Week 12
Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale
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.
Baseline up to Week 12
Percentage of Patients Achieving at Least 50% Pain Reduction at Week 12 on NRS 11 Point Scale
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.
Baseline up to Week 12
Mean Change in Insomnia Severity Index (ISI) From Baseline to Week 12
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.
Baseline up to Week 12
Change in Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 12
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.
Baseline up to Week 12
Plasma Pharmacokinetics (PK) Concentrations at Week 8 and 12
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
Week 8, Week 12
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)
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
Baseline, Week 8, Week 12
Treatment Emergent Adverse Events During Urgent Safety Measure (USM) Follow-Up
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
Approximately from 3 weeks after end of study up to 16 weeks
Klagenfurt
9020
Austria
Novartis Investigative Site
Vienna
A-1160
Austria
Novartis Investigative Site
Pellenberg
3212
Belgium
Novartis Investigative Site
Ontario
CAN
L4J 1W3
Canada
Novartis Investigative Site
Lévis
Quebec
G6W 5M6
Canada
Novartis Investigative Site
Québec
Quebec
G3K 2P8
Canada
Novartis Investigative Site
Brno
615 00
Czechia
Novartis Investigative Site
Choceň
56501
Czechia
Novartis Investigative Site
Plzen-Bory
305 99
Czechia
Novartis Investigative Site
Prague
100 00
Czechia
Novartis Investigative Site
Odense C
DK 5000
Denmark
Novartis Investigative Site
Boulogne-Billancourt
92104
France
Novartis Investigative Site
Clermont-Ferrand
63000
France
Novartis Investigative Site
Lille Cédex
59037
France
Novartis Investigative Site
Nice
06003
France
Novartis Investigative Site
Essen
North Rhine-Westphalia
45147
Germany
Novartis Investigative Site
Berlin
10435
Germany
Novartis Investigative Site
Dresden
01307
Germany
Novartis Investigative Site
Erlangen
91054
Germany
Novartis Investigative Site
Haar
85540
Germany
Novartis Investigative Site
Kiel
24105
Germany
Novartis Investigative Site
Kiel
24119
Germany
Novartis Investigative Site
Leipzig
04109
Germany
Novartis Investigative Site
Wiesbaden
65191
Germany
Novartis Investigative Site
Esztergom
HUN
2500
Hungary
Novartis Investigative Site
Kistarcsa
2143
Hungary
Novartis Investigative Site
Szeged
6725
Hungary
Novartis Investigative Site
Rome
00185
Italy
Novartis Investigative Site
Nishinomiya
Hyōgo
663 8014
Japan
Novartis Investigative Site
Yokohama
Kanagawa
241-0022
Japan
Novartis Investigative Site
Yokohama
Kanagawa
244-0816
Japan
Novartis Investigative Site
Yokohama
Kanagawa
245-8575
Japan
Novartis Investigative Site
Sakai
Osaka
593-8324
Japan
Novartis Investigative Site
Kawaguchi
Saitama
Japan
Novartis Investigative Site
Shizuoka
Shizuoka
420-0839
Japan
Novartis Investigative Site
Kasukabe-shi
Tokyo
343-0012
Japan
Novartis Investigative Site
Setagaya Ku
Tokyo
154-0015
Japan
Novartis Investigative Site
Ōita
Japan
Novartis Investigative Site
Oslo
0450
Norway
Novartis Investigative Site
Olsztyn
10 561
Poland
Novartis Investigative Site
Warsaw
00 144
Poland
Novartis Investigative Site
Almada
2801 951
Portugal
Novartis Investigative Site
Aveiro
3814-501
Portugal
Novartis Investigative Site
Leiria
2410-187
Portugal
Novartis Investigative Site
Lisbon
1500 650
Portugal
Novartis Investigative Site
Porto
4099-001
Portugal
Novartis Investigative Site
Dubnica nad Váhom
SVK
018 41
Slovakia
Novartis Investigative Site
Banská Bystrica
974 04
Slovakia
Novartis Investigative Site
Prešov
08001
Slovakia
Novartis Investigative Site
Spišská Nová Ves
05201
Slovakia
Novartis Investigative Site
Seongnam-si
Gyeonggi-do
463-712
South Korea
Novartis Investigative Site
L'Hospitalet de Llobregat
Barcelona
08907
Spain
Novartis Investigative Site
Barcelona
08025
Spain
Novartis Investigative Site
Tainan
70403
Taiwan
Novartis Investigative Site
Darlington
Durham
DL3 6HX
United Kingdom
Novartis Investigative Site
London
GBR
SW10 9NH
United Kingdom
Novartis Investigative Site
Liverpool
L9 7LJ
United Kingdom
FG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
FG003
EMA401 25mg BID -> EMA401 25mg BID TW
Participants on EMA401 25mg were randomized 1:1 to EMA401 25mg or placebo at end of treatment period (week 12)
FG004
EMA401 25mg BID -> Placebo BID TW
Participants on EMA401 25mg were randomized 1:1 to EMA401 25mg or placebo at end of treatment period (week 12)
FG005
EMA401 100mg BID -> EMA401 100mg BID TW
Participants on EMA401 100mg were randomized 1:1 to EMA401 100mg or placebo at end of treatment period (week 12)
FG006
EMA401 100mg BID -> Placebo BID TW
Participants on EMA401 100mg were randomized 1:1 to EMA401 100mg or placebo at end of treatment period (week 12)
FG007
Placebo BID -> Placebo BID TW
Participants on placebo remained on placebo at end of treatment period (week 12)
FG00043 subjects
FG00143 subjects
FG00243 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
COMPLETED
Study completers completed the treatment phase regardless of completion of study treatment.
FG00028 subjects
FG00130 subjects
FG00229 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
NOT COMPLETED
FG00015 subjects
FG00113 subjects
FG00214 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Type
Comment
Reasons
Study terminated by sponsor
FG00012 subjects
FG00110 subjects
FG00211 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Adverse Event
FG0003 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
FG004
Physician Decision
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG004
Treatment Withdrawal Period (TW)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00313 subjects
FG00413 subjects
FG00515 subjects
FG00613 subjects
FG00726 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00313 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
BG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
BG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00043
BG00143
BG00243
BG003129
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Number
participants
Title
Denominators
Categories
18 - 64 years
Title
Measurements
BG0004
BG0018
BG0027
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00020
BG00115
BG002
Race/Ethnicity, Customized
Number
participants
Title
Denominators
Categories
Caucasian
Title
Measurements
BG00033
BG00132
BG002
Body mass index
Median
Full Range
kg/m2
Title
Denominators
Categories
Title
Measurements
BG00025.9(18.4 to 36.4)
BG00125.2(17.4 to 33.0)
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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
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.
Due to premature study termination 300 mg BID dose was not initiated
Posted
Baseline up to Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
OG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
Units
Counts
Participants
OG0000
OG0010
OG0020
Secondary
Change in Weekly Mean 24-hour Average Pain Score Using the 11 Point Numerical Rating Scale (NRS) From Baseline to Week 12
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.
number of patients with observed change from baseline on respective visit.
Posted
Least Squares Mean
Standard Error
scores on a scale
Baseline up to Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
OG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
Secondary
Change in Brief Pain Inventory-Short Form Interference (BPI-SF) Mean Total Score From Baseline to Week 12
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
Posted
Mean
Standard Deviation
scores on a numeric rating scale
Baseline up to Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
OG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
Secondary
Change in Weekly Mean of the 24-hour Worst Pain Score, Using an 11-point NRS, From Baseline to Week 12
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.
Posted
Mean
Standard Deviation
scores on numeric rating scale
Baseline up to Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
OG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
Secondary
Number of Participants Per Patient Global Impression of Change Category at Week 12
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
Posted
Count of Participants
Participants
Baseline up to Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
OG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
Units
Counts
Participants
Secondary
Percentage of Patients Achieving at Least 30% Pain Reduction at Week 12 on NRS 11 Point Scale
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.
Full analysis set
Posted
Number
% of participants - model adjusted rate
Baseline up to Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
OG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
Secondary
Percentage of Patients Achieving at Least 50% Pain Reduction at Week 12 on NRS 11 Point Scale
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.
Full analysis set
Posted
Number
% of participants - model adjusted rate
Baseline up to Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
OG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
Secondary
Mean Change in Insomnia Severity Index (ISI) From Baseline to Week 12
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.
Full analysis set
Posted
Mean
Standard Deviation
scores on a scale
Baseline up to Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
OG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
Secondary
Change in Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 12
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.
Posted
Least Squares Mean
Standard Error
scores on a scale
Baseline up to Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
OG002
Placebo BID DB
Matching placebo capsules administered orally twice a day during double blind (DB) treatment period
Secondary
Plasma Pharmacokinetics (PK) Concentrations at Week 8 and 12
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
PK analysis set
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Week 8, Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
Units
Counts
Participants
OG000
Secondary
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)
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
Analysis was not performed
Posted
Baseline, Week 8, Week 12
ID
Title
Description
OG000
EMA401 25mg BID DB
Ema401 25 mg was administered orally twice a day during double blind (DB) treatment period
OG001
EMA401 100mg BID DB
Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period
Units
Counts
Participants
OG000
Secondary
Treatment Emergent Adverse Events During Urgent Safety Measure (USM) Follow-Up
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
The Overall Number of Participants Analyzed reflects the Safety population, regardless of whether they completed the study
Posted
Count of Participants
Participants
Approximately from 3 weeks after end of study up to 16 weeks
ID
Title
Description
OG000
EMA401 25mg BID -> EMA401 25mg BID
Participants on EMA401 25mg were randomized 1:1 to EMA401 25mg or placebo at end of treatment period (week 12)
OG001
EMA401 25mg BID -> Placebo BID
Participants on EMA401 25mg were randomized 1:1 to EMA401 25mg or placebo at end of treatment period (week 12)
OG002
EMA401 100mg BID -> EMA401 100mg BID
Participants on EMA401 100mg were randomized 1:1 to EMA401 100mg or placebo at end of treatment period (week 12)
OG003
EMA401 100mg BID -> Placebo BID
Time Frame
Adverse events were collected from first dose of study treatment until end of study treatment plus 21 days post treatment, up to maximum duration of 116 days
Description
Any sign or symptom that occurs during the study treatment plus the 21 days post treatment
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
EMA401 25 mg b.i.d.
EMA401 25 mg b.i.d.
0
43
0
43
8
43
EG001
EMA401 100 mg b.i.d.
EMA401 100 mg b.i.d.
0
43
3
43
12
43
EG002
Placebo b.i.d.
Placebo b.i.d.
0
43
3
43
14
43
EG003
EMA401 25 mg b.i.d. - EMA401 25 mg b.i.d.
EMA401 25 mg b.i.d. - EMA401 25 mg b.i.d.
0
13
1
13
0
13
EG004
EMA401 25 mg b.i.d. - Placebo b.i.d.
EMA401 25 mg b.i.d. - Placebo b.i.d.
0
13
0
13
1
13
EG005
EMA401 100 mg b.i.d. - EMA401 100 mg b.i.d.
EMA401 100 mg b.i.d. - EMA401 100 mg b.i.d.
0
15
0
15
2
15
EG006
EMA401 100 mg b.i.d. - Placebo b.i.d.
EMA401 100 mg b.i.d. - Placebo b.i.d.
0
13
0
13
1
13
EG007
Placebo b.i.d. - Placebo b.i.d.
Placebo b.i.d. - Placebo b.i.d.
0
26
0
26
1
26
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Angina pectoris
Cardiac disorders
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected43 at risk
EG0020 affected43 at risk
EG0031 affected13 at risk
EG0040 affected13 at risk
EG0050 affected15 at risk
EG0060 affected13 at risk
EG0070 affected26 at risk
Non-cardiac chest pain
General disorders
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected43 at risk
EG0021 affected43 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected43 at risk
EG0020 affected43 at risk
EG003
Traumatic haematoma
Injury, poisoning and procedural complications
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected43 at risk
EG0020 affected43 at risk
EG003
Electrocardiogram ST segment elevation
Investigations
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0011 affected43 at risk
EG0020 affected43 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected43 at risk
EG0021 affected43 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected43 at risk
EG0021 affected43 at risk
EG003
Central nervous system lymphoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected43 at risk
EG0021 affected43 at risk
EG003
Lumbar radiculopathy
Nervous system disorders
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected43 at risk
EG0021 affected43 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Diarrhoea
Gastrointestinal disorders
MedDRA (22.0)
Systematic Assessment
EG0003 affected43 at risk
EG0012 affected43 at risk
EG0023 affected43 at risk
EG0030 affected13 at risk
EG0040 affected13 at risk
EG0050 affected15 at risk
EG0060 affected13 at risk
EG0070 affected26 at risk
Dyspepsia
Gastrointestinal disorders
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0013 affected43 at risk
EG0021 affected43 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (22.0)
Systematic Assessment
EG0003 affected43 at risk
EG0012 affected43 at risk
EG0024 affected43 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0012 affected43 at risk
EG0023 affected43 at risk
EG003
Tongue injury
Injury, poisoning and procedural complications
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0010 affected43 at risk
EG0020 affected43 at risk
EG003
Amylase increased
Investigations
MedDRA (22.0)
Systematic Assessment
EG0001 affected43 at risk
EG0012 affected43 at risk
EG0020 affected43 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0012 affected43 at risk
EG0020 affected43 at risk
EG003
Lipase increased
Investigations
MedDRA (22.0)
Systematic Assessment
EG0001 affected43 at risk
EG0013 affected43 at risk
EG0020 affected43 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (22.0)
Systematic Assessment
EG0001 affected43 at risk
EG0011 affected43 at risk
EG0023 affected43 at risk
EG003
Headache
Nervous system disorders
MedDRA (22.0)
Systematic Assessment
EG0000 affected43 at risk
EG0012 affected43 at risk
EG0023 affected43 at risk
EG003
Post herpetic neuralgia
Nervous system disorders
MedDRA (22.0)
Systematic Assessment
EG0001 affected43 at risk
EG0010 affected43 at risk
EG0021 affected43 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.