A programme to develop a skin patch containing two medicines (physostigmine and hyoscine), Study 8: Assessment of effects of consecutive 24-hour applications of patches for 21 days on the blood levels of the two medicines and any associated symptoms in healthy male and female participants
| ISRCTN | ISRCTN62968791 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN62968791 |
| EudraCT/CTIS number | 2008-005286-58 |
| Secondary identifying numbers | RD 209/24774 |
- Submission date
- 15/04/2021
- Registration date
- 17/06/2021
- Last edited
- 10/06/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Injury, Occupational Diseases, Poisoning
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Background and study aims
A skin patch containing two medicines (physostigmine and hyoscine) has been developed. The skin patch releases these medicines enabling them to cross the skin into the bloodstream. The aim of this study is to measure the effect of daily application of the transdermal patch over 21 consecutive days on the amount of physostigmine and hyoscine delivered to the blood at different times.
Who can participate?
Healthy volunteers aged between 18 and 40 with either normal vision or requirements for glasses over a range of lens strengths.
What does the study involve?
Each participant wears a transdermal patch placed under an armband each day for 21 days. The patch is replaced each day. Blood samples are taken before and after patch application to measure the amounts of the two medicines (physostigmine and hyoscine). In addition, the activity of the enzyme acetylcholinesterase is measured in these blood samples. The condition of the skin under the patch is recorded at set times and any symptoms experienced while it was worn are noted. Heart rate, blood pressure, heart electrical activity, and vision and cognitive function tests are also recorded at set times.
What are the possible benefits and risks of participating?
There are no direct benefits for the participants. However, the information collected from the study will add to the scientific knowledge about the physostigmine and hyoscine patch. All medicinal products may cause side effects. The most common side effects known about the medicines in the patch are nausea and vomiting due to physostigmine and blurred vision and dry mouth due to hyoscine. Daily application of the transdermal patch for 21 consecutive days is considered to be well-tolerated.
Where is the study run from?
Simbec Research Limited (UK)
When is the study starting and how long is it expected to run for?
December 2007 to July 2012
Who is funding the study?
Ministry of Defence (UK)
Who is the main contact?
Defence Science and Technology Laboratory, Porton Down
centralenquiries@dstl.gov.uk
Contact information
Dr Medical Advisor
Scientific
Scientific
Defence Science and Technology Laboratory
Porton Down
Salisbury
SP4 0JQ
United Kingdom
| centralenquiries@dstl.gov.uk |
Study information
| Study design | Single-centre parallel-group double-blind placebo-controlled randomized study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Other |
| Participant information sheet | No participant information sheet available |
| Scientific title | A double-blind investigation of the effects of daily applications of the physostigmine and hyoscine transdermal patch (NAPS2 F11/21) with an armband on the pharmacokinetic (PK), pharmacodynamic (PD) and safety profiles over a 21-day period in healthy male and female Caucasian subjects |
| Study objectives | The study aim is to assess the effects of daily applications of the physostigmine and hyoscine F11/21 patch on pharmacokinetic, pharmacokinetic and safety profiles over a 21-day period in healthy male and female subjects. |
| Ethics approval(s) | Approved 27/01/2009, South East Wales Local Research Ethics Committees (LREC, Business Services Centre, Churchill House, 17 Churchill Way, Cardiff, CF10 2TW, UK; +44 (0)2920376820; Wales.REC1@wales.nhs.uk), ref: 09/WSE04/2 |
| Health condition(s) or problem(s) studied | Potential risk of poisoning by nerve agent |
| Intervention | Generic drug name: physostigmine and hyoscine (transdermal patch) Dosage: a daily (24 hour) application of active 21 cm² patch formulation F-11 (F11/21) or placebo, administered for 21 consecutive days. Randomization method: Stratified randomization took place, whereby subjects are randomized according to their equivalent spherical error in 1D (dioptre) bands. This is to ensure a full range of subjects were recruited with refractive errors throughout the range -1 to +4D. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Physostigmine, hyoscine |
| Primary outcome measure | 1. Plasma concentrations of physostigmine/hyoscine measured using liquid chromatography-tandem mass spectrometry (LC-MS-MS) on blood samples collected 12 hourly during the first 20 days and more frequently up to 54 hours after the final patch was applied. 2. Plasma concentrations of AchE measured using spectrophotometry on blood samples collected 12 hourly during the first 20 days and more frequently up to 54 hours after the final patch was applied 3. Safety measurements recorded before dosing and at intervals throughout the 21-day period of patch application up until 49 hours after final patch application: 3.1. Vital signs (supine blood pressure and pulse rate) measured using Good Clinical Practice (GCP)-validated automated blood pressure machine and pulse oximeter 3.2. Heart rhythm and electrical activity assessed from 12-lead ECGs recorded using GCP-validated electrocardiogram machine 3.3. Cognitive function measured using Bond-Lader visual analogue scale (VAS) of mood and alertness 3.4. Patch adhesion measured using digital photography |
| Secondary outcome measures | Ocular function measured by an optometrist by testing eye performance including visual acuity, refractive error, accommodation, intraocular pressure according to the following schedule: Baseline: on two consecutive days Dosing period: post patch application on days 2, 5, 10, 15 and 20 and 24 h and 48 h after last patch application Follow-up on two consecutive days |
| Overall study start date | 12/12/2007 |
| Completion date | 17/07/2012 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 54 |
| Total final enrolment | 54 |
| Key inclusion criteria | Screening: 1. Ability to give written informed consent prior to study participation 2. Healthy Caucasian male and female subjects aged between 18 and 40 years (inclusive) 3. Female subjects enrolled provided she: 3.1. Had a negative pregnancy test prior to entry into the study and: Either 3.2. Had a documented record of surgical sterilisation Or 3.3. Was of child-bearing potential and: 3.3.1. Agreed not to attempt to become pregnant during the study 3.3.2. Was routinely using an acceptable form of effective contraception (established use of oral, injected or implanted hormonal methods of contraception, intrauterine device (IUD) or intrauterine system (IUS), barrier method of contraception (condom or occlusive cap with spermicide), male sterilisation of sole partner; agreed to continue to do so during the study and for 28 days after study completion and agreed to use an additional barrier method for the duration of the study and for 28 days after study completion. (Hormonal contraception was not changed in the 3 months before the study). 3.3.3. Was not breastfeeding 4. Had a refractive error between -1 and +4 dioptres (D) spherical error and ≤1 D cylindrical error as measured by cycloplegic examination, habitually uncorrected 5. Had a spherical error between 1 D myopia and 4 D hyperopia. 6. Was able to read reduced Snellen type 6/9 at 35 cm (to exclude early presbyopia) 7. Had a best corrected visual acuity of 6/9 or better in each eye at 6 m 8. Had a near point stereopsis of 40 arc sec or better 9. Body Mass Index (BMI) within the range of ≥21 and ≤30 kg/m² 10. Vital signs with no clinically significant deviations outside the following ranges: 10.1. Heart rate 40-90 bpm 10.2. Systolic blood pressure 90-140 mmHg 10.3. Diastolic blood pressure 50-90 mmHg 11. Ability to communicate well with the Investigator and to comply with the requirements of the study (including contraception requirement) |
| Key exclusion criteria | Screening: 1. Presence of any clinically significant medical condition as determined by the Investigator 2. Any surgical or medical condition which might significantly alter 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. baseline prolongation of QT/QTc interval >450 ms 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. A dibucaine number of less than 70 6. History of asthma (within the previous 10 years), exercise-induced bronchospasm or relevant seasonal bronchospasm 7. Lung function of less than 80% of predicted FEV1 and FVC 8. Any history of contact dermatitis 9. Any skin disorder, broken skin, scars, tattoos at the sites of patch application (i.e. on both arms) 10. Glaucoma or a history of glaucoma in first-degree relatives (i.e. parents, siblings or offspring) 11. Presence of Anterior Chamber Narrow Angle (Van Herrick Grade 1 and 2) 12. Intra-ocular pressure exceeding 20 mm Hg 13. Habitual wearers of spectacles or contact lenses, although if they had been prescribed them in the past and did not use them, they could still be included 14. Astigmatism greater than 1 D cyl 15. History or evidence of drug abuse (opiates, methadone, cocaine, amphetamines, cannabinoids or 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 21 units (females) or 28 units (males) per week 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 last three months 20. Use of any prescription medication within the last 14 days (with the exception of hormonal contraception) 21. Use of non-prescription medication (apart from paracetamol and ibuprofen) within the last 7 days that could have an impact on the safety and objectives of the study (at the Investigator’s discretion). 22. 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. Baseline (all periods): 1. Development of any exclusion criteria since last visit 2. Positive urine test for alcohol 3. Positive drugs of abuse test 4. Positive pregnancy test 5. Use of any prescription medication since last visit (with the exception of hormonal contraception) 6. Use of non-prescription medication that may impact the safety aspects and objectives of the study, within the last 7 days (apart from paracetamol and ibuprofen) |
| Date of first enrolment | 27/01/2009 |
| Date of final enrolment | 04/09/2009 |
Locations
Countries of recruitment
- United Kingdom
- Wales
Study participating centre
Simbec Research Limited
-
Merthyr Tydfil
CF48 4DR
United Kingdom
Merthyr Tydfil
CF48 4DR
United Kingdom
Sponsor information
Defence Science and Technology Laboratory
Government
Government
Porton Down
Salisbury
SP4 0JQ
United Kingdom
| centralenquiries@dstl.gov.uk | |
"ROR" |
https://ror.org/04jswqb94 |
Funders
Funder type
Government
Ministry of Defence
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- MOD
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | As this study is part of a development program of several clinical studies to be submitted in a regulatory package to the MHRA for licence assessment, the researchers do not intend to publish this study separately. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to a lack of participant consent being obtained at the time of the study. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
15/04/2021: Trial's existence confirmed by the MHRA.
