Clinical study on pain reduction of the treatment

Placebo-controlled, randomised double-blind study with dimethicone and lidocaine comb. in patients with recurrent aphthous ulcers (1996/II)

A further double-blind study on patients with recurrent aphthous ulcers corresponding to

the design of the previously described study investigated the same DIHEC dispersion in

comparison with lidocaine (2 g in 100 g gel).

The study was conducted over a period of 14 days on a total of 297 patients of both

sexes ages 10 and up. All of them suffered from recurrent aphthous ulcers. Since the

therapeutic objective was pain reduction, only patients were incorporated who had

entered at least 3 cm on a visual analogue scale.

The examinations were conducted on treatment days 1, 2, 4, 7, 10 and 14 by ear, nose,

throat physicians, general practitioners, practitioners, internists, dermatologists, dentists

as well as paediatricians.

In addition to the recording of the development of the pain over the period, the recording

of the acute pain reduction 2, 3, 4, 5, 10, 20 and 30 minutes after local application of the

investigational product was also a target parameter.

The primary objective parameter was the development of pain intensity as of the

beginning of treatment, documented with a visual analogue scale up to the 4th day of

treatment.

The second primary objective parameter concerned the tolerability of the investigational

products.

The intensity of the pain decreased by 3.3 cm on the VAS by the fourth day of application

with dimethicone and hydroxyethyl cellulose. Patients who received lidocaine as a

therapeutic agent indicated a decrease of 3.6 cm. None of the differences were

significant. No significant differences in pain reduction were revealed, even by the 14th

day of treatment. All of the medicinal products produced a pronounced reduction in pain.

The analysis of the acute course of pain after local application of the investigational

products indicated that the reduction in pain took effect more quickly with the local

anaesthetic than with the other medicinal product, as was expected. In this regard,

lidocaine exhibited a significant superiority as compared with the DIHEC film-forming

substance combination at the 1st, 5th and 30th minute.

The diameter of the aphthous ulcers decreased in all patient groups over the 14-day

observation phase without resulting in significant differences. The same applied to the

healing of the aphthous ulcers, that is, complete morphological disappearance. The

proportion of healed aphthous ulcers amounted to over 80% in all patient collectives. If

one only takes the aphthous ulcers to be observed into consideration, this figure even

amounted to more than 87%. The mean duration of healing since the beginning of the

study amounted to less than 7 days for both treatment groups. None of the differences

were significant in this regard either.

No meaningful differences between the dispersion and lidocaine were revealed in the

investigating physicians’ global assessment concerning effectiveness. In the scope of the

investigations regarding the tolerability of the different medicinal preparations, evaluated

by the patients, the evaluation of the VAS scores indicated that the DIHEC film-forming

substance dispersion was perceived to be the most pleasant, followed by lidocaine.

No severe undesired effects came to light.

8 undesired events occurred in only 5 patients from the Bye Mouth Ulcer!™ group, which the

investigating physicians considered to be probably or possibly connected to the

investigational product.

Undesired effects such as tingling sensations, burning and numbness were indicated to a

great degree for lidocaine. However, this statement did not apply to the “burning”, which

was least frequently reported by the patients in the Bye Mouth Ulcer!™ group (DIHEC dispersion). 27

undesired events (29.3%) were registered with lidocaine, 7.6% of which were allocated to

“burning”.

This assessment is reflected in the physician’s assessment on tolerability. The dispersion

ended up with the best results. Lidocaine was rated as being considerably worse.

This double-blind randomised comparative study conducted permits to several important

conclusions to be made. It is conspicuous that the dimethicone complex of film-forming

substances yielded similarly reliable effects in the acute treatment of recurrent aphthous

ulcers as the local anaesthetic lidocaine. In principle, the investigational products also

exhibited the same effects in the long-term development of pain intensity. Since the

dispersion lacks a local anaesthetic effect in the sense of the definition, a different

mechanism of action must be at work here. Based on the considerations presented in the

introduction, one can assume that the effect of the aphthous ulcer pain is produced from

the covering affect at the base of the aphthous ulcer, not from the local anaesthetic effect.

Evaluation

The study described above was conceived, conducted and audited in accordance with

GCP and ICH guidelines, as was the investigation discussed on page 7, et seq.