Condition category
Injury, Occupational Diseases, Poisoning
Date applied
31/10/2019
Date assigned
05/11/2019
Last edited
01/11/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

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 was to measure the amount of physostigmine and hyoscine in the blood at different times, and assess any associated symptoms. The participants in the study were healthy male subjects with specific skin pigmentation

Who can participate?
Study participants were healthy males aged between 18 and 45 years with specific skin pigmentation

What does the study involve?
Each participant wore a transdermal patch for 72 hours on two different occasions separated by at least a week. On one occasion they wore a patch containing physostigmine and hyoscine, while on the other occasion they wore a placebo patch. Blood samples were 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 (AchE) was measured in these blood samples. The condition of the skin under the patch was recorded at set times and any symptoms experienced while it was worn were noted. Heart rate, blood pressure, the electrical activity of the heart (ECG), tests of vision and cognitive function were also recorded at set times

What are the possible benefits and risks of participating?
There were no direct individual benefits for the participants participating. However, the information collected from these individuals added to the scientific knowledge about the physostigmine and hyoscine patch. All medicinal products have a risk of causing 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. Overall the patch used was considered to be well tolerated

Where is the study run from?
The study was conducted at Simbec Research Limited

When is the study starting and how long is it expected to run for?
February 2006 to April 2007

Who is funding the study?
The study was funded by UK MoD

Contact details:
Defence Science and Technology Laboratory, Porton Down
centralenquiries@dstl.gov.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Medical Advisor

ORCID ID

Contact details

Porton Down
Salisbury
SP4 0JQ
United Kingdom
0000
centralenquiries@dstl.gov.uk

Additional identifiers

EudraCT number

2005-005492-15

ClinicalTrials.gov number

Nil known

Protocol/serial number

RD 209/24241

Study information

Scientific title

A Randomised, Double-Blind, Placebo-Controlled, Crossover Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Application of a Transdermal Patch Formulation of Hyoscine and Physostigmine in Healthy Male Subjects with Pigmented Skin of Grade 5 on the Fitzpatrick Skin Scale

Acronym

Study hypothesis

The aim of this study was to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple applications of a transdermal patch (21cm² area) in healthy male subjects with Fitzpatrick Grade 5 skin pigmentation

Ethics approval

Approved 16/02/2006, South East Wales Local Research Ethics Committees (LREC) (Churchill House, 17 Churchill Way, Cardiff, CF10 2TW; +44 (0)2920402402), ref: 06/WSE/04/13

Study design

Single centre randomized double-blind placebo-controlled 2-part crossover study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Other

Patient information sheet

No participant information sheet available

Condition

Potential risk of poisoning by nerve agent

Intervention

Generic drug name: physostigmine and hyoscine (transdermal patch)
Dosage: a single active or placebo 21cm2 patch formulation F-11.
Method and frequency of administration: a single dose of either active or placebo patch formulation F-11 was worn for 72 hours.
Randomisation: a sequential three-digit subject (randomisation) number was assigned once eligibility for the study was confirmed. Subjects were randomised to receive one of the two IMPs in Period 1 and the alternative in Period 2. Treatment was allocated according to the randomisation schedule produced by the CRO.

Intervention type

Drug

Phase

Phase I

Drug names

Physostigmine and hyoscine (transdermal patch)

Primary outcome measure

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 outcome measures

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

Overall trial start date

20/09/2005

Overall trial end date

23/04/2007

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Healthy volunteer

Age group

Adult

Gender

Male

Target number of participants

6

Participant 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

Recruitment start date

14/02/2006

Recruitment end date

07/06/2006

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Simbec Research Limited
Merthyr Tydfil
CF48 4DR
United Kingdom

Sponsor information

Organisation

Defence Science Technology Laboratory (Dstl)

Sponsor details

Porton Down
Salisbury
SP4 OJQ
United Kingdom
000
centralenquiries@dstl.gov.uk

Sponsor type

Other

Website

Funders

Funder type

Government

Funder name

Study conducted on behalf of UK Ministry of Defence

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Our intention is to submit the results of this study for publication in an academic journal later in the development programme

IPD sharing statement:
The datasets generated during and/or analysed during the current study are not expected to be made available due to confidentiality

Intention to publish date

31/12/2020

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

01/11/2019: Trial’s existence confirmed by the MHRA.