Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning
Conditions
Interventions
Each subject received 2 single applications of a transdermal patch containing physostigmine and hyoscine (150 g/m2) worn with an armband for 24 h over 2 periods (one application/period).
Sponsors
Dstl
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Able to give written informed consent prior to study participation 2. Healthy Caucasian male participants aged 18-40 years (inclusive). 3. Body mass index (BMI) within the range of =19 and =30 kg/m2. 4. Supine vital signs with no clinically significant deviations outside the following ranges: 4.1. Heart rate 40-90 bpm 4.2. Systolic blood pressure 90-140 mmHg 4.3. Diastolic blood pressure 50-90 mmHg 5. Agreement not to attempt to father a child during the study or for 3 months after treatment. Participants with a partner who could become pregnant must have agreed to use a reliable form of contraception during the trial and for 3 months afterwards, e.g. condom, established use of oral, injected or implanted hormonal contraceptive, intra-uterine device, diaphragm with spermicide. 6. Able to communicate well with the Investigator and to comply with the requirements of the study.
Exclusion criteria
Exclusion criteria: 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 considered to be clinically significant i.e. prolongation of QT/QTc interval >450 msec or history of additional risk factors for Torsades de Point (heart failure, hypokalemia, family history of long QT syndrome) 4. Known or suspected hypersensitivity or idiosyncratic reaction to any of the study products 5. History of asthma (within the previous 10 years), exercise-induced bronchospasm or relevant seasonal bronchospasm 6. Lung function of less than 80% of predicted forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) 7. Any history of contact dermatitis 8. Any skin disorder, broken skin, scars, tattoos at the sites of patch application (i.e. on both upper arms) 9. Glaucoma or a history of glaucoma in first-degree relatives (i.e. parents, siblings or offspring) 10. Presence of anterior chamber narrow angle (Van Herrick Grade 1 and 2) 11. Intraocular pressure exceeding 20 mmHg 12. Contact lens wearer 13. History or evidence of drug abuse (opiates, methadone, cocaine, amphetamines, cannabinoids or barbiturates) 14. Positive urine test for alcohol (test could have been repeated at baseline (Day -1 and Day 0), at the Investigator’s discretion) 15. History or evidence of alcohol abuse defined as an intake of more than 28 units per week where 1 unit corresponds to 250 ml beer, 20 ml spirits/liqueur or 100 ml of wine 16. Participation in a new chemical entity (NCE) clinical study within the last 4 months or a marketed drug clinical study within the previous 3 months. (N.B. Washout period between studies defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study.) 17. Use of any prescription medication within the last 14 days 18. Use of non-prescription medication (apart from paracetamol and ibuprofen) within the last 7 days that may have impacted on the safety and objectives of the study (at the Investigator’s discretion) 19. Donation of blood or blood products within the last 3 months, or the intention to donate blood or blood products within 3 months after completion of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma PK and intra-subject PK variability of physostigmine and hyoscine after single and multiple dosing of the PHP (150 g/m2): 1. Plasma concentrations of physostigmine measured at: Plasma PK at pre-determined times throughout both period 1 and period 2- Day 1 pre-dose, 3, 6, 9, 12, 15, 18, 21, 24 (Day 2), 27, 30, 33, 36, 39, 48 (Day 3), 72 (Day 4), 96 (Day 5) and follow-up (168 (Day 8) h post-dose). Assay method-liquid chromatography tandem mass spectrometry (LC-MS/MS) assay. 2. Plasma concentrations of hyoscine measured at: Plasma PK at pre-determined times throughout both period 1 and period 2 - Day 1 pre-dose, 3, 6, 9, 12, 15, 18, 21, 24 (Day 2), 27, 30, 33, 36, 39, 48 (Day 3), 72 (Day 4), 96 (Day 5) and follow-up (168 (Day 8) h post-dose). Assay method-liquid chromatography tandem mass spectrometry (LC-MS/MS) assay. | — |
Secondary
| Measure | Time frame |
|---|---|
| The local tolerability of the PHP (150 g/m2) transdermal patch and and its PD profile were measured using the assay method-spectrophotometric method to measure red cell acetylcholinesterase (AChE) activity. Activity was measured at pre-determined times throughout both period 1 and period 2- at baseline (Day -1 and Day 0), Day 1 pre-dose, 3, 6, 9, 12, 15, 18, 21, 24 (Day 2), 27, 30, 33, 36, 39, 48 (Day 3), 72 (Day 4) and follow-up (168 (Day 8) h post-dose). | — |
Countries
United Kingdom
Contacts
Public ContactMedical Advisor
Outcome results
None listed