Effects of dimethindene maleate nasal spray on the quality of life in seasonal allergic rhinitis.

OBJECTIVE: To determine if the H1-receptor antagonist dimethindene maleate (DMM), topically applied, is able to improve the quality of life (QoL) in patients with seasonal allergic rhinitis better than placebo. METHODS: The study was a multi-centre, randomised, placebo-controlled, double-blinded phase III trial including 157 patients. Two parallel groups received either DMM nasal spray or placebo for 2 weeks. Patients answered 5 QoL questionnaires (Rhinoconjunctivitis QoL Questionnaire (LQ-AR), Munich Life Dimension List (MLDL), Profile of Mood States (POMS), 2 Visual Analogue Scales (VAS-QoL, VAS-GES)) on days 1, 4, 8, and 15. RESULTS: QoL improved significantly in all scales and groups. Statistically significant differences between groups were achieved in the sub-scales LQ-AR Eye Symptoms and Daily Activities, MLDL Total, POMS Depression and Energy, VAS-QoL and VAS-General Health. All differences favoured the DMM group and were present initially but disappeared in visit 4, except MLDL Total and POMS Energy. Almost all other scores had a better tendency of DMM. CONCLUSION: A significant improvement of QoL was found in both groups. Only weak differences between groups (in favour of DMM) were found. There are several reasons explaining this outcome, mainly the rainy weather during the study period (mean weather index 10-20% less sunny than in previous seasons).

Dimethindene maleate in the treatment of sunburn. A double-blind, placebo-controlled pilot study.

The efficacy of topical dimethindene maleate (DMM, CAS 31614-69-5, Fenistil Gel) in the treatment of sunburn was evaluated in a placebo-controlled, 1-period crossover trial in 24 healthy volunteers. An UV-erythema (sunburn) of a well-defined intensity and extent was experimentally induced on three different skin test-areas by means of UV-A/B irradiation with three times the minimal erythema dose (MED). About 24 h after irradiation, one skin test-area was subjected to a 1-h occlusive treatment with DMM gel, the second test area was subjected to treatment with a placebo gel and the third one remained untreated. As objective-quantitative indicators of tenderness, a key symptom of sunburn, sensory and pain thresholds to CO2-Laser stimulation and laser somatosensory evoked potentials (SEPs) in Vertex-EEG were assessed about 1.5 h postdose. The reaction times (RTs) to painless and painful CO2-laser stimulation (sensory and pain threshold level, respectively) on the DMM-treated area were significantly longer than RTs to stimulation on the placebo-treated area. Thresholds in terms of laser energy showed no differences between the treatments. The SEP N1-amplitude on the DMM-area was markedly decreased in comparison to placebo. With regard to subjective sensations of pain, itching and tenderness assessed by means of visual analogue scales (VAS), no clinically relevant differences between treatments were observed after sole UV-irradiation. After additional laser stimulation tenderness was--objectively but not subjectively--decreased on the DMM-area versus placebo. Both gel preparations were well tolerated.

Efficacy of intranasally applied dimethindene maleate solution as spray in adult volunteers with symptoms of seasonal allergic rhinitis in the Vienna challenge chamber.

Twelve asymptomatic subjects (4 female, 8 male), being allergic to grass pollen proved by positive anamnesis, positive Prick-test and positive nasal provocation test, were challenged under controlled conditions with purified airborne grass pollen of Dactylis glomerata in the Vienna Challenge Chamber (VCC), located at the Universitätsklinik für Hals-Nasen-Ohrenheilkunde, Allgemeines Krankenhaus (AKH), der Stadt Wien, Vienna (Austria) by means of a double-blind, randomised, cross-over design, with 2 weeks wash-out periods between. Efficacy and safety of 2 concentrations of dimethindene (dimethindene maleate; DMM, CAS 3614-69-5, Fenistil resp. Foristal) 0.025% DMM, 0.1% DMM) were tested vs placebo as negative control and vs 0.1% azelastine as positive control, as topical nasal sprays. The tested nasal sprays were applied as single doses in the morning (2 puffs = 0.28 ml of the respective solution) to each nostril 15 min before the start of the 4 h lasting provocation procedure in the VCC, thus representing a total daily dose of 0.14 mg resp. 0.56 mg DMM and 0.56 mg azelastine, respectively. Compared to placebo, the objective variables nasal flow (150 Pa., measured by active anterior rhinomanometry) and nasal secretion (g), showed similar onset of antiobstructive and antisecretory effects in the nose after 0.1% DMM and 0.1% azelastine, respectively. The same applied for the subjective nasal symptom complex and for nasal symptom scores, evaluated by Visual Analog Scale (VAS): Time curves showed statistically significant and clinically relevant superiority of 0.1% DMM and 0.1% azelastine vs placebo, during the 4 h lasting provocation period. 0.025% DMM was not significantly different from placebo. No systemic adverse events were reported after the 4 tested preparations. Only a total of 3 subjects reported very slight local irritations (1 subject after placebo, 1 subject after 0.025% DMM and 1 subject after 0.1% azelastine). However, after 0.1% DMM no local adverse events were reported. It is concluded from this study that 0.1% DMM as nasal spray, is an efficient and safe galenical formulation for nasal spray application for patients suffering from seasonal allergic rhinitis (SAR).

Controlled exposure to mite allergen for a dose-finding of dimethindene maleate (DMM).

The aim of the study was to develop a laboratory system to challenge mite allergic patients with physiological concentrations of Der p I in order to evaluate the efficacy of antiallergic drugs in mite allergic patients. A double-blind, placebo-controlled, cross-over study was designed with three consecutive sessions. Twelve patients with proven sensitivity to dust mite were treated with a single dose of dimethindene maleate in a FOAD formulation (4 and 8 mg vs. placebo) 12 h before a long-term challenge with mite allergen Der p I in the Vienna challenge chamber. Challenge was performed with a constant concentration of 40 ng Der p I per cubic meter of air for 4 h. Nasal parameters were recorded at 15 min intervals during long-term challenge. In comparison to placebo, dimethindene leads to a statistically significant reduction (p < 0.05) of the nasal response at both concentrations tested. The house-dust mite model in the Vienna challenge chamber thus proved to be a useful tool for drug investigations in mite allergies.

Long-term polysomnographic study of the efficacy and safety of zolpidem in elderly psychiatric in-patients with insomnia.

The effects of 20 mg zolipidem were studied in an open, polysomnographically-monitored 179 day trial in 14 elderly psychiatric patients suffering from severe insomnia. After a placebo run-in of 7 days, zolpidem was given for 179 days followed by a 30-day wash-out period. Polysomnographic recordings (PSG) were performed just before active treatment; 30, 90 and 179 days into the treatment period; and at the end of the wash-out period. Statistically significant improvements in total sleep time, sleep efficiency and percentage of rapid eye movement sleep were observed after 30 days, all of which were maintained at 179 days. Sleep stages 1-4 all changed, with a significant decrease in percentage of stage 1, and a significant increase in both percentages of stage 2 and 3, and duration of stages 3 and 4 at the end of active treatment. After a 90-day follow-up period, only stage 3 sleep and sleep efficiency were no longer significantly changed compared to baseline, all other criteria showing maintenance of efficacy. Slow-wave sleep, which was increased during active treatment, decreased in the follow-up period. No serious adverse events were observed. These results suggest that, contrary to other hypnotics, zolpidem, after long-term administration, improves objective sleep parameters and may normalize a disturbed sleep architecture.

[Intravenous theophylline therapy. Effect of solubilizers on the incidence of adverse local effects in the area of infusion?]. / Intravenöse Theophyllintherapie. Einfluss des Lösungsvermittlers auf die Häufigkeit lokaler unerwünschter Wirkungen im Infusionsbereich?

The frequency and intensity of discomfort and pain at the site of injection during intravenous infusion of theophylline sodium glycinate and theophylline ethylenediamine were compared in a single blind crossover study on 6 healthy adult volunteers. The preparation containing theophylline sodium glycinate was significantly better tolerated than theophylline ethylenediamine.

[Clinical trial of febuprol, a new substance with choleretic activity. Study of efficacy and tolerability]. / Klinische Prüfung von Febuprol, einer neuen Substanz mit choleretischer Wirkung. Prüfung der Wirksamkeit und Verträglichkeit.

In a clinical trial, performed according to new criteria of the AMG (Arzneimittelgesetz) 1976, a new choleretic monosubstance 3-n-butoxy-1-phenoxy-2-propanol (code number: K 10.033, H 33, febuprol, Valbil) has been tested. The clinical investigations conducted on 712 healthy volunteers and patients within a period of 4 years showed that Valbil is an effective and safe drug. Besides the choleretic properties, febuprol has some additional spasmolytic and lipid lowering effects.

[Investigations to gastric tolerance of a sustained release theophylline formulation (author's transl)]. / Untersuchungen zur Magenverträglichkeit einer retardierten Theophyllin-Zubereitung.

The measurement of the transmural gastric potential difference (PD) is a suitable method to quantify irritations of the human gastric mucosa caused by drugs. Purpose of this investigation was to check the gastric tolerance of Bronchoretard, a new developed "divided-dose" drug formulation of theophylline as retarded pellets in capsules in comparison to pure theophylline solution. After having checked the suitability of the procedure in respect of the obtained results, a study on 7 healthy male volunteers was considered to be justifiable, as the development of retarded theophylline preparations, which cause lower irritations in the stomach by slower release of pure theophylline, has a high therapeutic value. With the gastric PD model, developed at our institute following variables were calculated: the area under the baseline (AUB), the "Reizindex" (RI), the mean instability time (MIT) of the membrane and the maximum potential difference (Pdmax). The volunteers wee admitted to the ward of our institute 36 h before the first application. On 2 different days 350 mg theophylline, dissolved in 50 ml physiological saline as well as 1 capsule Bronchoretard containing 350 mg theophylline, were administered Cross over according to a randomisation plan and the deviation of the PD was measured as a function of time. The study led to the following results: after administration of Bronchoretard the AUB is statistically significant smaller than after administration of theophylline solution (P less than 0.05). After administration of Bronchoretard the RI is statistically significant smaller than after administration of theophylline solution (p less than 0.05). After administration of Bronchoretard the mean instability time is statistically significant smaller than after administration of theophylline solution (p less than 0.05). After administration of Bronchoretard Pdmax is smaller in trend than theophylline solution (p greater than 0.05). The oral administration of Bronchoretard leads to considerably lower irritation than the instillation of the same dose of theophylline in solution.