| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Improvement of (hypertrophic)scar appearance |
|
| E.1.1.1 | Medical condition in easily understood language |
| Improvement of scar appearance |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10020879 |
| E.1.2 | Term | Hypertrophic scar |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of the study is to assess the safety and tolerance of topically applied salbutamol gel, when applied topically to the approximated wound margins of male and female subjects following surgical incisions. |
|
| E.2.2 | Secondary objectives of the trial |
| To determine the optimal concentration and efficacy of topical salbutamol gel, for the improvement of the resultant scar, when applied to the approximated wound margins of male and female subjects, following surgical incisions and daily thereafter, for 2 months. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Able, in the opinion of the investigator, and willing to give informed consent
2. Aged 18-50 inclusive, with both arms
3. Participants registered on the The Over Volunteering Prevention System (TOPS)or equivalent in Leicester.
4. Body mass index with the range of 15-35 kg per square metre
5. In the opinion of the investigator, clinically acceptable results for the laboratory tests specified in the trial protocol. All laboratory tests must be performed within 28 days of the subject's first trial dose administration.
6. Women of child bearing potential (WOCBP) must be using a highly effective* means of contraception and agree to do so from at least the screening visit until trial end or completion of the trial.
* Women of childbearing potential (WOCBP) will be required to use highly effective contraceptive measures (i.e. a failure rate of less than 1% per year when used consistently and correctly) before being enrolled into the study. In line with guidance, this has been clearly defined as:
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- oral
- intravaginal
- transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation:
- oral
- injectable
- implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion
• vasectomised partner (provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success)
• sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments).
|
|
| E.4 | Principal exclusion criteria |
1. On direct questioning, have evidence of Left/Right confusion
2. On direct questioning and/or physical examination a history or evidence of keloid scarring
3. On direct questioning have a family history of keloid scarring.
4. Tattoos or previous scars within 3cm of the area to be incised during the trial.
5. Surgery in the area to be incised and have surgical scars within 3cm of this area.
6. History of a bleeding disorder or who are receiving anti-coagulant or anti-platelet therapy.
7. On direct questioning and physical examination, have evidence of any past or present clinically significant disease that may affect the endpoints of the trial. For example coagulation disorders, diabetes, immuno-mediated conditions or allergies including contact dermatitis.
8. Subjects with a clinically significant skin disorder (dermatitis, eczema, psoriasis) that is chronic or currently active and which the investigator considers will adversely affect the healing of the acute wounds or involves the areas to be examined in this trial.
9. Any clinically significant medical condition or history that would impair wound healing including: Rheumatoid arthritis, chronic renal impairment for their age, hepatic impairment (LFTs >3 times upper limit of normal),congestive heart failure, pre-existing ischaemic heart disease, pulmonary hypertension, hypertrophic obstructive cardiomyopathy, aortic stenosis, current active malignancy or history of malignancy in the last 5 years, immunosuppression or chemotherapy within the last 12 months, a history of radiotherapy at the areas to be studies, diabetes mellitus, and subjects with a proven diagnosis of thyroid disease.
10. A history of hypersensitivity to any of the drugs or dressings used in the trial.
11. Other prescribed treatments including all corticosteroids, other salbutamol containing preparations, other beta-agonists, any beta-blockers, adrenaline.
12. Undergoing investigations or changes in management for an existing medical condition
13. History of drug abuse, including cocaine, amphetamines, methamphetamines, opiates or benzodiazepines.
14. In the opinion of the investigator, are unlikely to complete the trial for whatever reason
15. Any clinically significant neurological impairment or disease, including body dysmorphia.
16. At entry into the trial, any active infection
17. Pregnant or lactating or planning to become pregnant during the duration of the trial.
18. Not involved with any other clinical trial of medicinal product at the time of consent or 3 months prior. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary trial outcome will be
• Binary outcome of whether Salbutamol peak plasma concentration in the 24 hours following gel administration at day 0 is less than 30ng/ml or not
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The pharmacokinetic analysis will be assessed at 0 (baseline), 10, 30, 60 minutes and at 2, 4, 8 and 24 hours after first administration (day 0) and at 10, 30, 60 minutes and at 2, 4, 8 and 24 hours after Day 10 application |
|
| E.5.2 | Secondary end point(s) |
Secondary endpoints, will include:
• Binary outcome of whether Salbutamol peak plasma concentration in the 24 hours following gel administration at day 10 is less than 30ng/ml or not
•GSCS scores between drug and placebo, assessed by the clinical investigator at Month 7.
•GSCS scores between drug and placebo, assessed by the clinical investigator at Month 9.
•GSCS scores between drug and placebo, assessed by the clinical investigator at Month 12.
•GSCS scores between drug and placebo, assessed by the subject at Month 7.
•GSCS scores between drug and placebo, assessed by the subject at Month 9
•GSCS scores between drug and placebo, assessed by the subject at Month 12
•Differences in Patient & Observer Scar Assessment Scale (POSAS) scores at Month 9
•Differences in POSAS scores at Month 12
•Differences in objective assessments of scar colour, width, area and height (profilometry) at Month 9
•Differences in objective assessments of scar colour, width, area and height (profilometry) at Month 12
•Rate of local adverse events, between drug and placebo sites up to and including Month 3
•Rate of adverse events in first 3 months
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Secondary endpoints for safety (local adverse events) will be assessed at Month 3 (1 months after completion of dosing). Efficacy endpoints will be assessed between 7 and 12 months after surgery. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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