Efficacy and tolerability of a new powdered formulation of diclofenac potassium for oral solution for the acute treatment of migraine: results from the International Migraine Pain Assessment Clinical Trial (IMPACT).

OBJECTIVE: This study assessed the efficacy of diclofenac potassium for oral solution, a novel water-soluble buffered powder formulation, versus placebo for the acute treatment of migraine. Diclofenac potassium for oral solution has a time to maximum plasma concentration (Tmax) of 15 minutes, suggesting the potential for a rapid onset of therapeutic effects. METHODS: This was a randomized, double-blind, parallel-group, placebo-controlled study conducted in 23 US centers. Adult sufferers with an established migraine diagnosis according to the International Classification of Headache Disorders, second edition (ICHD-II), treated one moderate or severe attack with 50 mg diclofenac potassium for oral solution (dissolved in approximately 2 ounces of water; N=343) or matching placebo (N=347). Four co-primary endpoints included the percentage of subjects who at two hours post-treatment reported no headache pain, no nausea, no photophobia and/or no phonophobia. RESULTS: Significantly more subjects treated with diclofenac potassium for oral solution (N=343) achieved a two-hour pain-free response (25% vs. 10%, p<.001), no nausea (65% vs. 53%; p=.002), no photophobia (41% vs. 27%; p<.001) and no phonophobia (44% vs. 27%; p<.001) compared to placebo. Pain intensity differences between treatments were significantly lower in the diclofenac potassium oral solution group, starting at 30 minutes post-treatment (p=.013) with significant differences at all time points thereafter (p<.001). Twenty-four-hour sustained pain-free response favored diclofenac potassium oral solution treatment versus placebo (19% vs. 7%, p<.0001). The most common adverse event considered to be treatment related was nausea (diclofenac potassium for oral solution [4.6%]; placebo [4.3%]). CONCLUSIONS: This study shows that this formulation of diclofenac potassium for oral solution is effective in reducing pain intensity within 30 minutes, which may be related to the 15-minute T(max) associated with this formulation. The rapid-onset benefits were sustained through 24 hours post-treatment.

A double-blind, randomized, placebo-controlled, dose-finding study of oral pramiconazole in the treatment of pityriasis versicolor.

BACKGROUND: Pramiconazole is a broad-spectrum triazole antifungal with potential for oral treatment of pityriasis versicolor. OBJECTIVE: We sought to assess the efficacy and tolerability of 5 doses of pramiconazole relative to placebo. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, 28-day, dose-finding study. A total of 147 patients were randomized to treatment with placebo or one of 5 doses of pramiconazole; treatment lasted for 3 consecutive days. Efficacy was based on mycological response, severity of clinical signs and symptoms, and the Investigator Global Assessment of lesion clearance. RESULTS: A statistically significant (P < .001) dose-dependent effect was observed. When compared with placebo, a significant response (P < .05) was obtained for all but the lowest single dose of pramiconazole. There were no serious, treatment-related adverse events or other safety concerns. LIMITATIONS: The follow-up period was limited to 1 month after treatment onset. CONCLUSIONS: Pramiconazole is a well-tolerated and effective treatment for pityriasis versicolor and the most effective treatment regimen in this study included 200 or 400 mg taken once, and 200 mg taken once daily for 2 or 3 days.

Ketoconazole gel 2% in the treatment of moderate to severe seborrheic dermatitis.

Seborrheic dermatitis traditionally has been treated with topical steroids. In current practice, however, antifungal agents such as ketoconazole often are used because Malassezia yeasts are thought to play a role in the disease pathogenesis. Ketoconazole gel 2% has been developed for the once-daily treatment of seborrheic dermatitis. This gel is almost invisible after application, unlike ketoconazole cream, and may offer advantages in patient acceptance and adherence to treatment. Three randomized, double-blinded, vehicle-controlled, multicenter, parallel-group phase 3 studies evaluated the efficacy and tolerability of ketoconazole gel 2% compared with a vehicle gel in more than 900 subjects with moderate to severe seborrheic dermatitis who applied treatment for 14 days and were followed for an additional 14 days. Two of these studies also compared a combination gel containing ketoconazole 2% and desonide 0.05%, each active gel individually, and a vehicle control. Subjects were considered effectively treated if the erythema and scaling as well as investigator global assessment (IGA) scores decreased to 0 (or 1 if the baseline score was > or =3) by day 28. Pooled data from these studies showed that the proportion of effectively treated subjects was significantly greater in the ketoconazole gel 2% treatment group compared with the vehicle group (P < .001). The comparison of the combination gel to its individual components revealed that the efficacy of ketoconazole alone was comparable to the combination gel as well as desonide gel alone for up to 2 weeks after the end of treatment. These data suggest that once-daily ketoconazole gel 2% is an effective treatment for seborrheic dermatitis and a viable alternative to the ketoconazole cream 2% formulation.

Topical miconazole nitrate ointment in the treatment of diaper dermatitis complicated by candidiasis.

Diaper dermatitis (DD) complicated by candidiasis is a common problem in diaper-wearing infants and children. We report a double-blind, vehicle-controlled, parallel-group study evaluating the efficacy and safety of a low concentration of miconazole nitrate in a zinc oxide/petrolatum ointment for the treatment of DD complicated by candidiasis. Patients (N=330) who had DD with a severity score of 3 or higher were enrolled. Those patients with a baseline potassium hydroxide (KOH) preparation and a baseline culture specimen that both tested positive for Candida were retained for efficacy analysis (n=236). Miconazole nitrate 0.25% ointment or a zinc oxide/petrolatum vehicle control were applied to all clinically affected areas of patients with DD for 7 days at each diaper change and after bathing. A follow-up test-of-cure visit was conducted at day 14. Among the patients completing the study, the overall rate of cure (clinical cure plus microbiologic cure) was 23% for the miconazole nitrate group and 10% for the vehicle control group (P=.005); the rate of clinical cure (complete rash clearance, DD severity score=0 at day 14) was 38% for the miconazole nitrate group and 11% for the vehicle control group (P<.001); and the rate of microbiologic cure (no culture growth of Candida) was 50% for the miconazole nitrate group and 23% for the vehicle control group. The vehicle control resulted in mild improvement at day 3 but little or no subsequent improvement. The discontinuation rate due to clinical failure was substantially lower for the miconazole nitrate group (4%) than the vehicle control group (47%). The mean DD severity index score for the miconazole nitrate group was significantly lower from day 3 through day 14 compared with that of the vehicle control group (P<.001). Adverse events were assessed as either unlikely to be related to study medication or unrelated to study medication. By including only those patients with microbiologically confirmed Candida infection, the study population may not be fully indicative of patients treated for DD in routine clinical practice. Our data show that miconazole nitrate 0.25% ointment was well tolerated and significantly more effective than the zinc oxide/petrolatum vehicle control for treatment of DD complicated by candidiasis.

Aspirin is efficacious for the treatment of acute migraine.

BACKGROUND: More than 50% of migraine sufferers rely on over-the-counter medications for the treatment of migraine. Along with other over-the-counter products, aspirin is considered by the US Headache Consortium to be an option for first-line migraine treatment. This study assessed the efficacy and tolerability of aspirin versus placebo for the acute treatment of a single acute attack of migraine. METHODS: This prospective, randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy of a single, 1000-mg dose of aspirin for the treatment of acute moderate to severe migraine, with or without aura. Subjects recorded all study evaluations in a diary at baseline and at .5, 1, 2, 3, 4, 5, 6, and 24 hours after treatment. Pain was rated on a 4-point ordinal scale from no pain to severe pain. The primary efficacy end point was headache response at 2 hours. Secondary efficacy parameters included reduction of nausea, photophobia and phonophobia, pain intensity difference, and headache recurrence at 24 hours. RESULTS: Of 485 subjects enrolled, 409 took study medication and 401 treated a confirmed migraine attack (201 with aspirin and 200 with placebo). Baseline demographic and migraine characteristics were not significantly different between groups. The 2-hour headache response rate was 52% with aspirin versus 34% with placebo (P<.001). Aspirin was significantly more effective than placebo for pain reduction beginning 1 hour after dosing (P<.001) and continuing throughout the 6-hour evaluation period. Significantly (P<.05), more subjects were pain free from the 1-hour evaluation through the 6-hour evaluation. Of the aspirin-treated subjects, 20% were pain free at 2 hours versus only 6% of placebo-treated subjects. At 24 hours, the headache recurrence rate was 21.8% for aspirin (23 of 105 subjects) and 27.7% for placebo (19 of 68 subjects). Only 34% of aspirin-treated subjects needed rescue medication at 24 hours compared with 52% of placebo-treated subjects (P<.001). Aspirin was well tolerated, and adverse events were not significantly different between groups. CONCLUSIONS: This study demonstrates that aspirin is safe and effective for treatment of acute migraine in appropriately selected patients.

The pharmacokinetics of nebulized nanocrystal budesonide suspension in healthy volunteers.

Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg were approximately dose proportional with respect to Cmax, AUC(0-t), and AUC(0-infinity). Nanobudesonide 0.5 mg and Pulmicort Respules 0.5 mg exhibited similar AUCs, suggesting a similar extent of pulmonary absorption. A higher Cmax was noted with nanobudesonide 0.5 mg, and the tmax was significantly different, suggesting a more rapid rate of drug delivery of nanobudesonide 0.5 mg than Pulmicort Respules. In conclusion, nebulized nanobudesonide 0.5 mg was safe in healthy volunteers, with a similar extent of absorption as Pulmicort Respules.