Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning
Conditions
Interventions
Generic drug name: physostigmine and hyoscine (transdermal patch)
Dosage: a single active or placebo 21cm2 patch formulation F-11.
Method and frequency of administratio
Sponsors
Defence Science Technology Laboratory (Dstl)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Screening: 1. Ability to give written informed consent prior to study participation 2. Healthy male subjects with pigmented skin of Grade 5 on the Fitzpatrick skin scale 3. Aged between 18 and 45 years (inclusive) 4. Body Mass Index (BMI) within the range of 21and 30 kg/m2 5. Vital signs within the following ranges: 5.1. Pulse rate 40-90 bpm 5.2. Systolic blood pressure 90- 150 mmHg 5.3. Diastolic blood pressure 50- 95 mmHg 6. Ability to communicate well with the Investigator and to comply with the requirements of the study Baseline Period 2: 1. Successful completion of Period 1 2. Willingness to continue in the study
Exclusion criteria
Exclusion criteria: Screening: 1. Presence of any clinically significant medical condition as determined by the Investigator 2. Any surgical or medical condition which might have significantly altered the absorption, distribution, metabolism or excretion of any drug (e.g. renal or liver disease, respiratory, immunological, endocrine or neurological disorders) 3. Any ECG abnormality (sinus bradycardia and respiratory sinus arrhythmia are considered to be normal findings in healthy young adults) 4. Known or suspected hypersensitivity or idiosyncratic reaction related to any of the study products 5. Any history of contact dermatitis 6. A dibucaine number of less than 70 7. Skin disorders, broken skin, scars or tattoos that were extensive enough to obscure the patch application sites on both arms 8. Glaucoma or a history of glaucoma in first degree relatives (i.e. parents, siblings or offspring) 9. Presence of Anterior Chamber Narrow Angle (Van Herrick Grade 1 and 2) 10. Intra-ocular pressure exceeding 20 mm Hg 11. Uncorrected vision in both eyes of worse than 6/9 on the Snellen Scale 12. Required glasses or contact lenses for distance vision 13. History of asthma (within the previous 10 years), exercise induced bronchospasm or relevant seasonal bronchospasm 14. Lung function of less than 80% of predicted FEV1 and FVC values. 15. History or evidence of drug abuse (opiates, methadone, cocaine, amphetamines, methamphetamines, cannabinoids, barbiturates) 16. Positive test for HIV, Hepatitis B or Hepatitis C 17. History or evidence of alcohol abuse defined as an intake of more than 28 units per week (4 units per day), where 1 unit corresponds to 250 ml beer, 20 ml spirits/liqueur or one glass (100 ml) of wine 18. Positive urine test for alcohol 19. Participation in another clinical study within the previous three months 20. Use of any prescription medication within the previous 14 days 21. Use of non-prescription medication within the previous seven days (apart from paracetamol) 22. Donation of blood or blood products within the previous three months, or the intention to donate blood or blood products within three months after completion of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safety and tolerability of a single application of physostigmine/hyoscine transdermal patch formulation was assessed by monitoring vital signs, ECG, ocular function (near point), patch application site assessment, using digital photography. These parameters were measured at baseline and at pre-determined intervals up to 96 hours after patch application and at follow up | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) and pharmacodynamic (PD) profiles were measured at regular time points at screening, pre-dose and up to 96 hours after patch application. Physostigmine and hyoscine plasma levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS) method. Acetylcholinesterase levels measured by validated spectrophotometric method | — |
Countries
United Kingdom
Contacts
Public ContactMedical Advisor
Outcome results
None listed