Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning
Conditions
Interventions
1. Generic drug name: physostigmine and hyoscine (transdermal patch)
2. Dosage: study planned as single dose (72-hour application) three-way crossover
3. Method and fre
Sponsors
Dstl
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Healthy male participants 2. Aged between 18 and 40 years inclusive 3. Body Mass Index (BMI) = 18 and = 31 kg/m2, and body weight = 60 and = 110 kg 4. Able to understand the informed consent discussion, which included information about potential risks and effects of the test materials, and signed the informed consent form 5. Medical history without major pathology (e.g. cardiac, immunological, endocrine or neurological disorders, cancer or other wasting diseases) 6. Human immunodeficiency virus (HIV), hepatitis B and hepatitis C negative 7. No clinically significant abnormalities at the pre-study screening, and subject’s GP had not advised against inclusion 8. Computerised 12-lead ECG recording without clinically relevant signs of pathology and conductance disturbances as judged by the investigator
Exclusion criteria
Exclusion criteria: 1. Presence of any clinically significant medical condition as determined by the investigator 2. Known or suspected hypersensitivity or idiosyncratic reaction related to any of the test materials 3. Homozygous or heterozygous for the atypical (dibucaine resistant) allele of butyrylcholinesterase 4. Any skin disorder, broken skin, scars, tattoos at the site of application 5. Glaucoma or a history of glaucoma in first degree relatives (i.e. parents, siblings and offspring) 6. Presence of Anterior Chamber Narrow Angle (Van Herrick Grade 1 and 2) 7. Intra-ocular pressure exceeding 20 mm Hg 8. Uncorrected vision (or contact lens corrected vision) in either eye worse than 6/9 on the Snellen scale 9. History or evidence of drug abuse (including opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates) 10. History or evidence of alcohol abuse defined as intake of more than 21 units per week (3 units per day), where 1 unit corresponds to 250 mL beer, 20 mL spirits/liqueur or one glass (100 mL) of wine 11. Participation in another clinical trial within three months prior to the start of the study 12. Use of any prescription medication within two weeks, or non-prescription medication (e.g. acetylsalicylic acid/paracetamol) within 48 hours, prior to dosing 13. Regular drug intake during the month prior to the start of the study 14. History or suspicion of inability to co-operate adequately 15. Donation of blood or blood products for a period of four weeks prior to and four weeks after completion of the study 16. History of asthma (or history of asthma within the previous 10 to 15 years, at investigator’s discretion) 17. History of exercise-induced bronchospasm, or relevant seasonal bronchospasm 18. Lung function (FEV1) less than 80% of predicted spirometry criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Plasma concentrations of hyoscine and physostigmine measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS)): blood samples collected at the following times: 0 hours (pre-dose) and 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after patch application on Day 1, 2, 4, 6, 8, 10, 12 and 24 hours after patch removal 2. Acetylcholinesterase activity measured by spectrophotometry: blood samples collected at the following times: Day –1, 0 hours (pre-dose) and 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after patch application on Day 1; 2, 4, 6, 8, 10, 12 and 24 hours after patch removal | — |
Secondary
| Measure | Time frame |
|---|---|
| Adhesion score measured by visual inspection of degree of patch adhesion to skin at 24 and 48 hours after application | — |
Countries
United Kingdom
Contacts
Public ContactMedical Advisor
Outcome results
None listed