Post-herpetic Neuralgia Clinical Trial
— EMPHENEOfficial 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
Verified date | October 2021 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
Status | Terminated |
Enrollment | 130 |
Est. completion date | March 7, 2019 |
Est. primary completion date | March 7, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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%. |
Country | Name | City | State |
---|---|---|---|
Australia | Novartis Investigative Site | Melbourne | Victoria |
Austria | Novartis Investigative Site | Klagenfurt | |
Austria | Novartis Investigative Site | Vienna | |
Belgium | Novartis Investigative Site | Pellenberg | |
Canada | Novartis Investigative Site | Levis | Quebec |
Canada | Novartis Investigative Site | Ontario | CAN |
Canada | Novartis Investigative Site | Quebec | |
Czechia | Novartis Investigative Site | Brno | |
Czechia | Novartis Investigative Site | Chocen | |
Czechia | Novartis Investigative Site | Plzen-Bory | |
Czechia | Novartis Investigative Site | Praha 10 | |
Denmark | Novartis Investigative Site | Odense C | |
France | Novartis Investigative Site | Boulogne Billancourt | |
France | Novartis Investigative Site | Clermont-Ferrand | |
France | Novartis Investigative Site | LILLE Cédex | |
France | Novartis Investigative Site | Nice | |
Germany | Novartis Investigative Site | Berlin | |
Germany | Novartis Investigative Site | Dresden | |
Germany | Novartis Investigative Site | Erlangen | |
Germany | Novartis Investigative Site | Essen | Nordrhein Westfalen |
Germany | Novartis Investigative Site | Haar | |
Germany | Novartis Investigative Site | Kiel | |
Germany | Novartis Investigative Site | Kiel | |
Germany | Novartis Investigative Site | Leipzig | |
Germany | Novartis Investigative Site | Wiesbaden | |
Hungary | Novartis Investigative Site | Esztergom | HUN |
Hungary | Novartis Investigative Site | Kistarcsa | |
Hungary | Novartis Investigative Site | Szeged | |
Italy | Novartis Investigative Site | Rome | |
Japan | Novartis Investigative Site | Kasukabe-shi | Tokyo |
Japan | Novartis Investigative Site | Kawaguchi-city | Saitama |
Japan | Novartis Investigative Site | Nishinomiya | Hyogo |
Japan | Novartis Investigative Site | Oita | |
Japan | Novartis Investigative Site | Sakai | Osaka |
Japan | Novartis Investigative Site | Setagaya ku | Tokyo |
Japan | Novartis Investigative Site | Shizuoka-shi | Shizuoka |
Japan | Novartis Investigative Site | Yokohama | Kanagawa |
Japan | Novartis Investigative Site | Yokohama | Kanagawa |
Japan | Novartis Investigative Site | Yokohama-shi | Kanagawa |
Korea, Republic of | Novartis Investigative Site | Seongnam-si | Gyeonggi-do |
Norway | Novartis Investigative Site | Oslo | |
Poland | Novartis Investigative Site | Olsztyn | |
Poland | Novartis Investigative Site | Warszawa | |
Portugal | Novartis Investigative Site | Almada | |
Portugal | Novartis Investigative Site | Aveiro | |
Portugal | Novartis Investigative Site | Leiria | |
Portugal | Novartis Investigative Site | Lisboa | |
Portugal | Novartis Investigative Site | Porto | |
Slovakia | Novartis Investigative Site | Banska Bystrica | |
Slovakia | Novartis Investigative Site | Dubnica nad Vahom | SVK |
Slovakia | Novartis Investigative Site | Presov | |
Slovakia | Novartis Investigative Site | Spisska Nova Ves | |
Spain | Novartis Investigative Site | Barcelona | |
Spain | Novartis Investigative Site | L Hospitalet De Llobregat | Barcelona |
Taiwan | Novartis Investigative Site | Tainan | |
United Kingdom | Novartis Investigative Site | Darlington | Durham |
United Kingdom | Novartis Investigative Site | Liverpool | |
United Kingdom | Novartis Investigative Site | London | GBR |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Norway, Poland, Portugal, Slovakia, Spain, Taiwan, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
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. | Baseline up to Week 12 | |
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. | Baseline up to Week 12 | |
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 | Baseline up to Week 12 | |
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. | Baseline up to Week 12 | |
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 | Baseline up to Week 12 | |
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. | Baseline up to Week 12 | |
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. | Baseline up to Week 12 | |
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. | Baseline up to Week 12 | |
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. | Baseline up to Week 12 | |
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 | Week 8, Week 12 | |
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 | Baseline, Week 8, Week 12 | |
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 | Approximately from 3 weeks after end of study up to 16 weeks |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT01944150 -
Association of Transcutaneous Electrical Nerve Stimulation and Hypnosis
|
N/A | |
Completed |
NCT00159666 -
Study of Pregabalin Therapy for Pain Relief in Subjects With Post-Herpetic Neuralgia
|
Phase 4 | |
Completed |
NCT00305357 -
Evolution of Pain From Herpes Zoster
|
||
Not yet recruiting |
NCT03120962 -
Effect of Early Use of Oxycodone During the Acute Phase of Herpes Zoster on Preventing Postherpetic Neuralgia
|
N/A | |
Completed |
NCT02701374 -
Efficacy and Safety of TRK-700 in Patient With Post-Herpetic Neuralgia
|
Phase 2 | |
Completed |
NCT02318719 -
DS-5565 Phase III Study for Post-herpetic Neuralgia
|
N/A | |
Completed |
NCT01752699 -
Methadone in Post-Herpetic Neuralgia Pain
|
Phase 3 | |
Completed |
NCT01250561 -
Reduction of Postherpetic Neuralgia in Herpes Zoster
|
N/A | |
Completed |
NCT02607280 -
DS-5565 Phase III Study for Renal Impairment in Japanese Subjects
|
Phase 3 | |
Completed |
NCT01037088 -
Effects of Vaporized Marijuana on Neuropathic Pain
|
Phase 1/Phase 2 | |
Completed |
NCT02633306 -
Transcranial Magnetic Stimulation for Facial Pain
|
N/A | |
Recruiting |
NCT05593237 -
Transcranial Magnetic Stimulation for Chronic Neuropathic Pain
|
N/A | |
Completed |
NCT01848730 -
Efficacy and Safety of CNV2197944 Versus Placebo in Patients With Post-herpetic Neuralgia
|
Phase 2 |