Pilot Proof of Concept Study of NBMI Treatment of Mercury Intoxication

Study Overview
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Brief Summary
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A randomized, placebo controlled, double blind proof of concept study of NBMI in treatment of mercury intoxication.

Detailed Description
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The objectives of this study are to evaluate the efficacy and safety of two doses of NBMI compared to placebo in mercury intoxicated patients.

Official Title
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A Randomized, Placebo-controlled Study to Explore Safety, Dose and Efficacy of NBMI in a Mercury Intoxicated Population

Conditions
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Mercury Poisoning

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 18 and 65 years, inclusive. Urine-Hg ≥ 15 μg/L. Mercury intoxication medical score sum (Doering et al. 2014) ≥ 5 or medical score sum ≥ 3 in combination with at least two of the following symptoms; social nervousness/withdrawal, irritability, memory loss, metallic taste, mental- and physical fatigue. Has signed informed consent for participation. Willingness and ability to comply with study procedures, visit schedules, and other instructions regarding the study. Exclusion criteria 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. Known or a medical history of renal disorder, significant renal failure, or high risk of renal failure. Any clinically significant abnormalities in clinical chemistry or haematology results at the time of screening as judged by the investigator. Known or suspected neurodegenerative disorder including but not limited to stroke, polio, Parkinson's and Alzheimer's disease. Known or suspected drug or alcohol abuse. Positive pregnancy test in women. Serious bacterial and chronic viral infection such as human immunodeficiency virus (HIV) or hepatitis virus. History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, as judged by the investigator or 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). Participation in any other clinical study that included drug treatment within three months of the first administration of investigational product. Use of other therapies for mercury intoxication including metal chelators within three months. Investigator considers subject unlikely to comply with study procedures, restrictions and requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NBMI (Emeramide) 100mg<br>NBMI oral capsules 100mg administered once daily. Double dummy used for blinding i.e. 2 x 50mg NBMI + 1 x 200mg placebo capsule equals in total 3 capsules administered daily. | Drug: Emeramide<br>* Mercury chelator NBMI ((N1,N3-bis(2-mercaptoethyl) isophthalamide)<br>* Other names: Irminix;|
| Experimental: NBMI (Emeramide) 300mg<br>NBMI oral capsules 300mg administered once daily. Double dummy used for blinding i.e. 2 x 50mg NBMI + 1 x 200mg NBMI capsule equals in total 3 capsules administered daily. | Drug: Emeramide<br>* Mercury chelator NBMI ((N1,N3-bis(2-mercaptoethyl) isophthalamide)<br>* Other names: Irminix;|
| Placebo Comparator: Placebo<br>Placebo oral capsules administered once daily. Double dummy used for blinding i.e. 2 x 50mg size + 1 x 200mg size placebo capsules equal in total 3 capsules administered daily. | Drug: Placebo<br>* NBMI Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mercury Intoxication Medical Score Sum | Changes from baseline in mercury intoxication medical score sum compared between treatment arms. | 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual components of Mercury Intoxication Medical Score Sum | Changes from baseline in individual components of the mercury intoxication medical score sum compared between treatment arms. | 45 days | 
| Fatigue score | Changes from baseline in fatigues score sum compared between treatment arms. | 15 days | 
| Neuromotoric functions | Changes from baseline in neuromotoric functions objectively assessed and quantified using computerized systems such as CATSYS compared between treatment arms. | 45 days | 
| Blood mercury levels | Changes from baseline in blood mercury level compared between treatment arms. | 45 days | 
| Urine mercury levels | Changes from baseline in urine mercury level compared between treatment arms. | 45 days | 
| NBMI blood levels | NBMI blood levels 0-24 hours after the first and last dose (day 14 dose) | 14 days | 
| NBMI urine levels | NBMI urine levels 0-24 hours after the first and last dose (day 14 dose) | 14 days | 
| Adverse events | Adverse event frequency, type and severity compared between treatment arms. | 45 days | 
| Safety laboratory assessments | Changes from baseline in clinical chemistry and haematology tests compared between treatment arms. | 45 days | 
| Vital signs | Changes from baseline in vital signs compared between treatment arms. | 45 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mercury toxicity poisoning