Clinical studie on treatment

Monocentric, randomised study with dimethicone and lidocaine in HIV patients with oral

mucosal lesions and oral ulcerations (1996)

A DIHEC dispersion was compared with lidocaine in a randomised, monocentric, singleblind (the patient could not recognise the active substance or comparative product) study in HIV patients suffering from oral mucosal lesions or oral ulcerations. It must be critically noted that it could not be discerned from the study documents which illnesses were subsumed under “oral mucosal lesions”. The target parameters were the effectiveness and tolerability of the DIHEC film-forming substance combination. 40 patients were incorporated, of which 20 received the film-forming substance combination (16 mg per day maximum) as a gel and 20 received lidocaine gel (40 mg per day). 6 patients in the Bye Mouth Ulcer!™ group (DIHEC dispersion) and 5 patients in the lidocaine group discontinued the study prematurely. 

Upon being incorporated into the study, there were 63 aphthous ulcers among the 20 dimethicone film-forming substance combination patients and 76 aphthous ulcers among the lidocaine patients (intent to treat). 

One of the primary objective parameters was pain reduction. They were recorded 10 minutes before and 10 minutes after application of the investigational product with the help of a visual analogue scale. The dimethicone hydroxyethyl cellulose application lead to a percental decrease in pain intensity of 71.4% on examination date 1 and 88.7% with the lidocaine patients. The differences were not significant. The effect lasting from day 1 to day 2 was more pronounced with Bye Mouth Ulcer!™, while the increase in pain was lower for the Bye Mouth Ulcer!™ group (pain intensity prior to application on day 2 was 4.84) than for the lidocaine group (pain intensity prior to application on day 2 was 5.17). After the application the pain intensity reduced significantly in the favour of Bye Mouth Ulcer!™ (0.66) in comparison with lidocaine (0.70). By investigation day 4, pain decreased by 62.2% or 4.20 cm in the Bye Mouth Ulcer! ™ group and by 23.8% (2.96 cm) in the lidocaine group. In a one-sided interview, the difference in the absolute reduction was significantly in favour of the dimethicone hydroxyethyl cellulose film-forming substance complex, the percental difference was statistically insignificant but medically relevant.

The analysis of the patients per protocol indicated aphthous ulcer healing during treatment of 90% with the DIHEC complex (39 aphthous ulcers treated) and 100% for the lidocaine patients. The duration of healing was somewhat shorter for the lidocaine group, although this difference was also not significant.

Lidocaine performed markedly better overall in a subjective medical evaluation of the effectiveness. The acute course of pain after treatment by a physician only exhibited conspicuous differences in lidocaine’s favour on the first day; both products produced an equivalent effect on the following days. Undesired effects occurred in 8 patient in the Bye Mouth Ulcer!™ group (10 undesired events) and in 1 patient (1 undesired event) in the lidocaine group. Burning was mostly reported, as was one instance of numbness. No connection was established between other undesired events such as acute bronchitis and the medication. It was considered probably that the burning and paresthesia were connected to the investigational product. To summarise, it can be established that dimethicone is also effective for aphthous ulcers in HIV patients. In comparison with the local anaesthetic lidocaine, the intensity of the treatment was somewhat less pronounced in the acute phase, but the long-term pain reduction was significantly better. Bye Mouth Ulcer!™ clearly possesses a pain-abating effect on aphthous ulcers in HIV patients is well, but its mechanism of action cannot be clarified based on this study. A local anaesthetic effect such as that with lidocaine can be ruled out, since the DIHEC dispersion does not produce an anaesthetising effect on intact oral mucosa like lidocaine does.

Evaluation

This study is a unicentric, randomised, single-blind comparative phase III study between a DIHEC film-forming substance combination and lidocaine. The study was planned and conducted in accordance with the rules of Good Clinical Practice and the rules of the International Conference of Harmonisation (ICH). A placebo-controlled study was rejected for ethical reasons, since the patients with aphthous ulcers were infected with HIV. These patients, who suffer from extremely painful aphthous ulcers, cannot be deprived of treatment. The therapeutic agents preferred in treating aphthous ulcers are predominately available as topical pharmaceutical forms. In addition to the specific material components of the effect, there was also the physical covering effect, which expresses itself as a pain-abating effect. A physical mechanism of action is currently being discussed with Bye Mouth Ulcer!™, so the double-dummy technique (lidocaine + dimethicone dispersion as placebo or Bye Mouth Ulcer!™ + lidocaine-free base) was consequently not used. The investigation was therefore planned as a single-blind study. Even if the tubes of the comparative preparation were “blinded” by sticking opaque labels on them, the investigating physician was given the chance to differentiate between the two products based on the size of the tube, etc. The sponsor consciously accepted the limitation of this design, meaning that the results described in the preceding must be seen in consideration of this aspect. The success of treatment of both therapy forms ultimately made itself clear.

The investigational products’ undesired events reported must also be discussed under the assumption that aphthous ulcers are greater in size and number in HIV patients than in is the case in aphthous ulcer patients who are not infected with HIV. This aspect is particularly relevant in evaluation of the unwanted side-effects after application of the active substance, such as “burning”.