NBMI - Clinical Study on COPD

Study Overview
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Brief Summary
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A pilot study to explore safety of the treatment with the antioxidant and metal chelator NBMI in COPD patients. Investigational product: NBMI ((N1,N3-bis(2-mercaptoethyl) isophthalamide), INN: Emeramide Indication: Mild, moderate and severe COPD with bronchitis A randomised, two arm, double-blind, placebo-controlled, cross-over, once daily for 14 days pilot study in subjects with COPD with bronchitis.

Official Title
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A Randomised, Placebo-controlled, Blinded, Cross-over, Pilot Study to Explore Safety and Efficacy of NBMI Treatment of Patients With Mild, Moderate and Severe Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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COPD, COPD Bronchitis

Intervention / Treatment
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* Drug: Emeramide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects, age between 45 and 75 years, including Ex-smokers, who quit smoking > 6 months prior to screening visit, with a smoking history of at least 10 pack years Diagnosis of COPD according to GOLD stages I-III, i.e. Post-beta-2-agonist FEV1/FVC < 0.70 and Post-beta-2-agonist FEV1 >30 % of predicted value Active symptomatic COPD with a total COPD assessment test (CAT) score >10 Bronchitis with cough and sputum production during many days of the last month, and at least three months during the last year Has signed informed consent for participation Willingness and ability to comply with study procedures, visit schedules, and other instructions regarding the study. Exclusion Criteria: Patient with > 2 COPD exacerbation requiring treatment with systemic corticosteroids and/or antibiotics or hospitalization within the last year Patient with COPD exacerbation requiring treatment with systemic corticosteroids and/or antibiotics or hospitalization within the last 4 weeks New medication or change of dose for COPD treatment within 4 weeks prior to randomisation (chronic treatment with stable dose is allowed) Ongoing treatment with systemic steroids, antibiotics, oxygen treatment, N-acetylcysteine (NAC) or roflumilast within 4 weeks of randomisation Clinically significant heart failure, heart infarction, stroke or TIA within 12 months of study screening Ongoing treatment with warfarin at screening visit Ongoing treatment with medications that are metabolised or eliminated through the CYP P450 system, which could cause a drug interaction with the investigational product, as judged by the investigator, within 2 weeks of randomisation Ongoing treatment with metal containing medications, such as iron supplement, lithium medications or antacids, within 2 weeks of randomisation History of alcohol abuse or substance/drug abuse within 12 months prior to screening visit History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subjects at risk because of participation in the study, or influence the results or the subject's ability to participate in the study Any clinically significant abnormalities in clinical chemistry or haematology results at the time of screening, as judged by the investigator Total alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine > upper limit of normal (ULN) at screening History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, as judged by the investigator, including history of hypersensitivity to drugs with a similar chemical structure or class to NBMI History of allergy/hypersensitivity to bisulphites (e.g. red/white wine) Women of child bearing potential who do not consent to using acceptable methods of contraception (i.e. one of the following: combined hormonal contraception and progestogen-

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A randomised, two arm, double-blind, placebo-controlled, cross-over, once daily for 14 days and 28 days follow up
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>14 days treatment with NBMI 300 mg/day | Drug: Emeramide<br>* Lipophilic, membrane passing Metal chelator and anti oxidant<br>* Other names: Irminix;|
| Placebo Comparator: Placebo<br>14 days treatment with Placebo | Drug: Placebo<br>* 14 days treatment with placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability - Adverse events | To evaluate the safety and tolerability of NBMI daily oral administration for 14 days in patients with mild, moderate and severe COPD. Adverse events in terms of frequency and severity compared to placebo treatment. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cough - Changes from baseline in Leicester cough questionnaire compared to placebo treatment | To investigate the efficacy of NBMI daily oral administration for 14 days on cough in patients with moderate and severe COPD. Changes from baseline in Leicester cough questionnaire compared to placebo treatment. | 14 days | 
| Individual symptoms CAT - Changes from baseline in COPD assessment (CAT) test compared to placebo treatment | To investigate the efficacy of NBMI daily oral administration for 14 days on changes from baseline in COPD assessment (CAT) test compared to placebo treatment. | 14 days | 
| Individual symptoms mMRC - Changes from baseline in modified Medical Research Council (mMRC) dyspnoea scale compared to placebo treatment | To investigate the efficacy of NBMI daily oral administration for 14 days on changes from baseline in in modified Medical Research Council (mMRC) dyspnoea scale compared to placebo treatment | 14 days | 
| Individual symptoms 6 min walking test - Changes from baseline in 6 Minute walk test measurements compared to placebo treatment | To investigate the efficacy of NBMI daily oral administration for 14 days on changes from baseline in 6 Minute walk test measurements compared to placebo treatment | 14 days | 
| Individual symptoms MDP - Changes from baseline in Multidimensional Dyspnoea Profile (MDP) compared to placebo treatment | To investigate the efficacy of NBMI daily oral administration for 14 days on changes from baseline in Multidimensional Dyspnoea Profile (MDP) compared to placebo treatment | 14 days | 
| Laboratory - Changes from baseline of standard haematology and clinical chemistry laboratory analyses (e.g. blood, kidney, liver, infections) compared to placebo treatment | To investigate the efficacy of NBMI daily oral administration for 14 days on changes from baseline of standard haematology and clinical chemistry laboratory analyses (e.g. blood, kidney, liver, infections) compared to placebo treatment | 14 days | 
| Vital signs - Changes from baseline of vital signs (incl. oxygen saturation (spO2), blood pressure, pulse, body weight) compared to placebo treatment | To investigate the efficacy of NBMI daily oral administration for 14 days on changes from baseline of vital signs (incl. oxygen saturation (spO2), blood pressure, pulse, body weight) compared to placebo treatment | 14 days | 
| Lung function FEV - Changes from baseline in pre-, post-bronchodilator and FVC compared to placebo treatment. | To investigate the efficacy of NBMI daily oral administration for 14 days on lung function in patients with mild, moderate and severe COPD on changes from baseline in pre-, post-bronchodilator and FVC compared to placebo treatment. | 14 days | 
| Lung function St George - Changes from baseline in St George´s respiratory questionnaire compared to placebo treatment | To investigate the efficacy of NBMI daily oral administration for 14 days on lung function in patients with mild, moderate and severe COPD on changes from baseline in St George´s respiratory questionnaire compared to placebo treatment | 14 days |