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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-000281-39 | EudraCT Number |
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Study was terminated due to animal toxicity data
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The purpose of this study is to evaluate safety and efficacy of EMA401 compared to placebo in patients with painful diabetic neuropathy (PDN).
This was an interventional, randomized, parallel, placebo-controlled, double-blind treatment study consisting of 3 periods i.e. Screening, Treatment, and Treatment withdrawal. Patients were planned to be randomized in a 1:1 ratio to Placebo b.i.d. or EMA401 100 mg b.i.d.. Concomitant use of pregabalin or duloxetine at stable doses was allowed. Based on historical data, it was planned that the study would enroll approximately 50% of patients who were on stable doses of concomitant pregabalin or duloxetine in the study. At the end of treatment period the 100mg b.i.d. arm was 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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EMA401 | Experimental | During the treatment epoch, patients will receive EMA401 for 12 weeks. During the treatment withdrawal epoch, patients will receive EMA401 or matching placebo for 1 week. |
|
| Placebo | Placebo Comparator | Participants will receive matching placebo to EMA401 during both the treatment and treatment withdrawal epochs for a total of 13 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EMA401 | Drug | capsules, oral |
| |
| Placebo |
| 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. | Baseline up to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
At the time of Screening, must have had documented diagnosis of Type I OR Type II diabetes mellitus (DM) with painful distal symmetrical sensorimotor neuropathy (ICD-10 code G63.2) of more than 6 months duration with any one or more of the following:
Been assessed as suffering from moderate to severe neuropathic pain across the Screening epoch (NRS ≥ 4).
A score of ≥4 on the Douleur Neuropathique en 4 Questions (DN4) questionnaire at Screening.
Exclusion Criteria:
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception during dosing and for 3 days after stopping of study medication. Highly effective contraception methods included:
History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study.
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.
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.
Participants whose glycemic control had been unstable within 3 months immediately prior to screening (e.g., ketoacidosis requiring hospitalization, any recent episode of hypoglycemia requiring assistance through medical intervention, uncontrolled hyperglycemia)
Patients who had any differential diagnosis of PDN including but not limited to other neuropathies (e.g. Vitamin B12 deficiency, Chronic Inflammatory Demyelinating Polyneuropathy), polyradiculopathies, central disorders (e.g. demyelinating disease), or rheumatological disease (e.g., foot arthritis, plantar fasciitis).
Patient was unwilling or unable to complete daily eDiary.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Broadmeadow | New South Wales | 2292 | Australia | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33675631 | Derived | 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. |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicaltrials.com | View source |
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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.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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Three hundred six patients were screened and 137 randomized
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| ID | Title | Description |
|---|---|---|
| FG000 | EMA401 100mg BID DB | Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period |
| FG001 | Placebo BID DB | Matching placebo capsules administered orally twice a day during double blind (DB) treatment period |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Double-Blind Treatment Period (DB) |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 15, 2017 | Mar 20, 2020 |
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| Drug |
Placebo to EMA401 capsules, oral |
|
| Baseline up to Week 12 |
| 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 scale with zero being "does not interfere" and ten being "completely interferes". The BPI total score is the sum of the 7 items. Each item ranges from 0 to 10, thus the total score ranges from 0 to 70. Lower values indicate a better outcome. | 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% 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. 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. The scale consists of 7 items. The sum of seven items represents the total score. Each of the 7 items is scored using a range from 0 to 4, thus the total score values ranges from zero to 28. 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 (Prior dose, 1-3 hours, 4-6 hours), Week 12 (Prior dose, 1-3 hours, 4-6 hours) |
| Percentage of Patients Who Required Rescue Medication in Double-blind Treatment Period | Patients were allowed to take acetaminophen/paracetamol up to a maximum of 3 g daily (divided into 4 times/day) for unacceptable pain due to any reason during the study. This medication use was to be recorded in eDiary prior to use. Percentages of patients presented are those who required rescue meds within 7 days prior to visit. | Baseline and weekly up to 12 weeks, once during double-blind period |
| Percentage of Patients Who Required Rescue Medication in Treatment Withdrawal Period | Patients were allowed to take acetaminophen/paracetamol up to a maximum of 3 g daily (divided into 4 times/day) for unacceptable pain due to any reason during the study. This medication use was to be recorded in eDiary prior to use. Percentages of patients presented are those who required rescue meds within 7 days prior to visit. | Week 12 to Week 13 (planned duration subject to varibility in visit scheduling) |
| Time to First Rescue Medication Intake | Patients were allowed to take acetaminophen/paracetamol up to a maximum of 3 g daily (divided into 4 times/day) for unacceptable pain due to any reason during the study. This medication use was to be recorded in eDiary prior to use. Patients who did not take any rescue medication were censored at the last date of double-blind treatment period. | Baseline up to day 92 |
| 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 |
| Orange |
| New South Wales |
| 2800 |
| Australia |
| Novartis Investigative Site | Adelaide | South Australia | 5000 | Australia |
| Novartis Investigative Site | Heidelberg Heights | Victoria | 3081 | Australia |
| Novartis Investigative Site | Graz | A-8036 | Austria |
| Novartis Investigative Site | Klagenfurt | 9020 | Austria |
| Novartis Investigative Site | Vienna | A-1090 | Austria |
| Novartis Investigative Site | Edegem | 2650 | Belgium |
| Novartis Investigative Site | Liège | 4000 | Belgium |
| Novartis Investigative Site | Pellenberg | 3212 | Belgium |
| Novartis Investigative Site | Sofia | Sofia-Grad | 1336 | Bulgaria |
| Novartis Investigative Site | Sofia | 1000 | Bulgaria |
| Novartis Investigative Site | Sofia | 1407 | Bulgaria |
| Novartis Investigative Site | Sofia | 1431 | Bulgaria |
| Novartis Investigative Site | Ontario | CAN | L4J 1W3 | Canada |
| Novartis Investigative Site | Thornhill | Ontario | L4J 8L7 | Canada |
| Novartis Investigative Site | Toronto | Ontario | M4G 3E8 | Canada |
| Novartis Investigative Site | Laval | Quebec | H7T 2P5 | Canada |
| Novartis Investigative Site | Aarhus | 8000 | Denmark |
| Novartis Investigative Site | Gentofte Municipality | DK 2820 | Denmark |
| Novartis Investigative Site | Odense C | DK 5000 | Denmark |
| Novartis Investigative Site | Tampere | FIN-33520 | Finland |
| Novartis Investigative Site | Boulogne-Billancourt | 92104 | France |
| Novartis Investigative Site | Bielefeld | D 33647 | Germany |
| Novartis Investigative Site | Düsseldorf | 40225 | Germany |
| Novartis Investigative Site | Essen | 45147 | Germany |
| Novartis Investigative Site | Halle | 06120 | Germany |
| Novartis Investigative Site | Kassel | Germany |
| Novartis Investigative Site | Kiel | 24119 | Germany |
| Novartis Investigative Site | Leipzig | 04109 | Germany |
| Novartis Investigative Site | Wiesbaden | 65191 | Germany |
| Novartis Investigative Site | Debrecen | HUN | 4032 | Hungary |
| Novartis Investigative Site | Esztergom | HUN | 2500 | Hungary |
| Novartis Investigative Site | Szeged | HUN | 6720 | Hungary |
| Novartis Investigative Site | Balatonfüred | 8230 | Hungary |
| Novartis Investigative Site | Budapest | 1085 | Hungary |
| Novartis Investigative Site | Budapest | 1089 | Hungary |
| Novartis Investigative Site | Kistarcsa | 2143 | Hungary |
| Novartis Investigative Site | Pécs | 7632 | Hungary |
| Novartis Investigative Site | Szeged | 6725 | Hungary |
| Novartis Investigative Site | Oslo | 0450 | Norway |
| Novartis Investigative Site | Krakow | POL | 31 505 | Poland |
| Novartis Investigative Site | Bialystok | 15-351 | Poland |
| Novartis Investigative Site | Warsaw | 00 144 | Poland |
| Novartis Investigative Site | Caldas da Rainha | 2500 176 | Portugal |
| Novartis Investigative Site | Lisbon | 1250 203 | Portugal |
| Novartis Investigative Site | Matosinhos Municipality | 4454 509 | Portugal |
| Novartis Investigative Site | Porto | 4200 319 | Portugal |
| Novartis Investigative Site | Viana do Castelo | 4901858 | Portugal |
| Novartis Investigative Site | Vila Nova de Gaia | 4434 502 | Portugal |
| Novartis Investigative Site | Lučenec | Slovak Republic | 98401 | Slovakia |
| Novartis Investigative Site | Bratislava | 83305 | Slovakia |
| Novartis Investigative Site | Bratislava | 85101 | Slovakia |
| Novartis Investigative Site | Prešov | 080 01 | Slovakia |
| Novartis Investigative Site | Prešov | 08001 | Slovakia |
| Novartis Investigative Site | Seville | Andalusia | 41014 | Spain |
| Novartis Investigative Site | Madrid | 28222 | Spain |
| Novartis Investigative Site | Bradford | West Yorkshire | BD9 6RJ | United Kingdom |
| Novartis Investigative Site | Bath | BA1 3NG | United Kingdom |
| Novartis Investigative Site | Bournemouth | BH7 7DW | United Kingdom |
| Novartis Investigative Site | Edinburgh | EH4 2XU | United Kingdom |
| Novartis Investigative Site | London | SE1 7EH | United Kingdom |
| Novartis Investigative Site | Middlesbrough | TS4 3BW | United Kingdom |
| Novartis Investigative Site | Oldham | OL1 2JH | United Kingdom |
| FG002 | EMA401 100mg BID -> EMA401 100mg BID TW | Participants on EMA401 100mg were randomized 1:1 to EMA401 100mg or placebo at end of DB treatment period (week 12) |
| FG003 | EMA401 100mg BID -> Placebo BID TW | Participants on EMA401 100mg were randomized 1:1 to EMA401 100mg or placebo at end of DB treatment period (week 12) |
| FG004 | Placebo BID -> Placebo BID TW | Participants on placebo remained on placebo at end of DB treatment period (week 12) |
| COMPLETED | Study completers completed the treatment phase regardless of completion of study treatment. |
|
| NOT COMPLETED |
|
|
| Treatment Withdrawal Period (TW) |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | EMA401 100mg BID DB | Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period |
| BG001 | Placebo BID DB | Matching placebo capsules administered orally twice a day during double blind (DB) treatment period |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
| |||||||||||||||||||
| Body mass index | Median | Full Range | kg/m^2 |
|
| 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 | 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. | Full analysis set | Posted | Least Squares Mean | Standard Error | scores on a scale | Baseline up to Week 12 |
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| 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 |
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| 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 scale with zero being "does not interfere" and ten being "completely interferes". The BPI total score is the sum of the 7 items. Each item ranges from 0 to 10, thus the total score ranges from 0 to 70. Lower values indicate a better outcome. | Posted | Mean | Standard Deviation | scores on a scale | Baseline up to Week 12 |
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| 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 |
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| 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 |
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| 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% 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 |
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| 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 |
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| 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. 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. The scale consists of 7 items. The sum of seven items represents the total score. Each of the 7 items is scored using a range from 0 to 4, thus the total score values ranges from zero to 28. Lower values represent better outcomes. | Full analysis set | Posted | Mean | Standard Deviation | scores on a scale | Baseline up to Week 12 |
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| 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 (Prior dose, 1-3 hours, 4-6 hours), Week 12 (Prior dose, 1-3 hours, 4-6 hours) |
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| Secondary | Percentage of Patients Who Required Rescue Medication in Double-blind Treatment Period | Patients were allowed to take acetaminophen/paracetamol up to a maximum of 3 g daily (divided into 4 times/day) for unacceptable pain due to any reason during the study. This medication use was to be recorded in eDiary prior to use. Percentages of patients presented are those who required rescue meds within 7 days prior to visit. | Full analysis set | Posted | Number | Percentage of participants | Baseline and weekly up to 12 weeks, once during double-blind period |
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| Secondary | Percentage of Patients Who Required Rescue Medication in Treatment Withdrawal Period | Patients were allowed to take acetaminophen/paracetamol up to a maximum of 3 g daily (divided into 4 times/day) for unacceptable pain due to any reason during the study. This medication use was to be recorded in eDiary prior to use. Percentages of patients presented are those who required rescue meds within 7 days prior to visit. | Full analysis set | Posted | Number | Percentage of participants | Week 12 to Week 13 (planned duration subject to varibility in visit scheduling) |
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| Secondary | Time to First Rescue Medication Intake | Patients were allowed to take acetaminophen/paracetamol up to a maximum of 3 g daily (divided into 4 times/day) for unacceptable pain due to any reason during the study. This medication use was to be recorded in eDiary prior to use. Patients who did not take any rescue medication were censored at the last date of double-blind treatment period. | Full analysis set | Posted | Median | Full Range | days | Baseline up to day 92 |
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| 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 |
|
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 111 days
Any sign or symptom that occurs during the study treatment plus the 21 days post treatment are reported in adverse event (AE) section. Upon termination of study, participants were instructed to attend two unscheduled visits for follow-up safety assessments for Urgent Safety Measure (USM) follow-up. Adverse events collected during USM are not included in this AE section but reported in secondary outcome measure 13 entitled Treatment Emergent Adverse Events During Urgent Safety Measure Follow-up
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | EMA401 100mg BID DB | Ema401 100 mg was administered orally twice a day during double blind (DB) treatment period | 0 | 69 | 5 | 69 | 23 | 69 |
| EG001 | Placebo BID DB | Matching placebo capsules administered orally twice a day during double blind (DB) treatment period | 0 | 66 | 3 | 66 | 10 | 66 |
| EG002 | EMA401 100mg BID -> EMA401 100mg BID TW | Participants on EMA401 100mg were randomized 1:1 to EMA401 100mg or placebo at end of DB treatment period (week 12) | 0 | 14 | 0 | 14 | 1 | 14 |
| EG003 | EMA401 100mg BID -> Placebo BID TW | Participants on EMA401 100mg were randomized 1:1 to EMA401 100mg or placebo at end of DB treatment period (week 12) | 0 | 12 | 0 | 12 | 2 | 12 |
| EG004 | Placebo BID -> Placebo BID TW | Participants on placebo remained on placebo at end of DB treatment period (week 12) | 0 | 26 | 0 | 26 | 0 | 26 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Product intolerance | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
| Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 18, 2019 | Mar 20, 2020 | SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D003929 | Diabetic Neuropathies |
| D009437 | Neuralgia |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C000595242 | EMA400 |
Not provided
Not provided
Not provided
| Title | Measurements |
|---|---|
|
| ≥ 85 years |
|
| Male |
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| Asian |
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| Other |
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| Week 12 |
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