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).
Kyrein
H J
HJ
Zyma GmbH, Clinical Development, Munich Germany.
Horak
F
F
Nirnberger
G
G
Rehn
D
D
D000281:Administration, Intranasal; D000328:Adult; D000336:Aerosols; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001273:Atmosphere Exposure Chambers; D018592:Cross-Over Studies; D004115:Dimethindene / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage; D006801:Humans; D008297:Male; D010793:Phthalazines / Q000008:administration & dosage; D010865:Pilot Projects; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy*
D000336:Aerosols; D018926:Anti-Allergic Agents; D006634:Histamine H1 Antagonists; D010793:Phthalazines; D004115:Dimethindene; C020976:azelastine