A glycopyrronium bromide 1% cream for topical treatment of primary axillary hyperhidrosis: efficacy and safety results from a phase IIIa randomized controlled trial.
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ABSTRACT: Background
Effective topical treatment options for patients with primary axillary hyperhidrosis (PAHH) are limited. A phase I trial showed promising results regarding the efficacy and safety of a topical cream containing glycopyrronium bromide (GPB).Objectives
To assess the efficacy, safety and tolerability of a 4-week topical treatment of GPB 1% cream in patients with PAHH vs. placebo.Methods
In total, 171 patients (84 receiving placebo; 87 receiving GPB 1%) with PAHH were included in the 4-week, multicentre, randomized, double-blind, placebo-controlled phase IIIa part of the pivotal study. Sweat production was measured by gravimetry. Patients rated the impact of disease with the Hyperhidrosis Disease Severity Scale (HDSS) and Hyperhidrosis Quality of Life Index (HidroQoL© ).Results
Absolute change in sweat production from baseline to day 29 in logarithmic values was significantly larger in the GPB 1% group compared with the placebo group (P = 0·004). The improvement in HidroQoL exceeded the minimal clinically important difference of 4. The proportion of responders was twofold higher for sweat reduction (-197·08 mg GPB 1% vs. -83·49 mg placebo), HDSS (23% GPB 1% vs. 12% placebo) and HidroQoL (60% GPB 1% vs. 26% placebo). Treatment was safe: most treatment-emergent adverse effects were mild or moderate, and transient. Local tolerability was very good, with 9% of patients having only mild or moderate application-site reactions. The most reported adverse drug reaction was dry mouth (16%), an expected anticholinergic effect of the treatment.Conclusions
GPB 1% cream may provide an effective new treatment option exhibiting a good safety profile for patients with PAHH. The long-term open-label part (phase IIIb) is ongoing.
SUBMITTER: Abels C
PROVIDER: S-EPMC8451866 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundGlycopyrronium tosylate (GT; Qbrexza® [glycopyrronium] cloth, 2.4%) is a topical anticholinergic approved (USA) for primary axillary hyperhidrosis in patients aged ≥ 9 years.ObjectiveThe objective of this study was to compare the pharmacokinetics and safety of GT to oral glycopyrrolate (phase I study) and assess the relationship between glycopyrronium pharmacokinetics and anticholinergic-related adverse events or efficacy with population pharmacokinetics using data from two phase II studies.MethodsIn the phase I study, study staff applied GT to axillae of patients with primary axillary hyperhidrosis (aged 9-65 years) once daily (5 days); oral glycopyrrolate was administered to healthy adults (aged 18-65 years) every 8 hours (15 days). In the phase II studies (NCT02016885 [20 December, 2013], NCT02129660 [2 May, 2014]), adults with primary axillary hyperhidrosis applied topical glycopyrronium (0.8-3.2%) or vehicle to axillae once daily (4 weeks). Pharmacokinetic and adverse event data were collected in all studies.ResultsGlycopyrronium pharmacokinetic parameters were similar between adult and pediatric patients treated with GT; there was no evidence of accumulation. Systemic absorption of glycopyrronium was lower with GT vs oral glycopyrrolate. No anticholinergic-related adverse events occurred with GT in the phase I study, while dry mouth and nasal dryness occurred with oral glycopyrrolate; anticholinergic adverse events occurred in the phase II studies. In the population pharmacokinetic analysis, frequency/severity of anticholinergic-related adverse events increased with higher glycopyrronium concentration; no relationship was observed between efficacy and pharmacokinetic measures.ConclusionsThese studies indicate limited absorption of GT compared to oral glycopyrrolate and a low risk of anticholinergic adverse events with proper GT administration when following instructions for use (wipe each underarm once with same cloth, wash hands, avoid ocular contact).
| S-EPMC8113176 | biostudies-literature
Project description:BACKGROUND:Glycopyrronium tosylate is a topical anticholinergic approved in the USA for primary axillary hyperhidrosis in patients aged???9 years (Qbrexza™ [glycopyrronium] cloth, 2.4%). OBJECTIVE:This 44-week open-label extension study assessed glycopyrronium tosylate safety and descriptive efficacy in patients completing one of two, phase III, double-blind, vehicle-controlled, 4-week trials (NCT02530281; NCT02530294). METHODS:Patients aged???9 years with primary axillary hyperhidrosis were randomized 2:1 (glycopyrronium tosylate: vehicle, once daily) in the double-blind trials. Completers could receive open-label glycopyrronium tosylate for up to an additional 44 weeks. Treatment-emergent adverse events and local skin reactions were assessed. Descriptive efficacy assessments were gravimetrically measured sweat production, Hyperhidrosis Disease Severity Scale responder rate (??2 grade improvement), and Dermatology Life Quality Index/children's Dermatology Life Quality Index. RESULTS:Of 651 patients completing the double-blind trials, 564 (86.6%) entered the open-label extension; 550 were analyzed. Most patients experiencing treatment-emergent adverse events had mild or moderate events (>?90%). Discontinuation because of treatment-emergent adverse events remained low and relatively stable, with a cumulative rate of 8.0% (44/550) over 44 weeks. Common treatment-emergent adverse events (>?5%) were dry mouth (16.9%), vision blurred (6.7%), application-site pain (6.4%), nasopharyngitis (5.8%), and mydriasis (5.3%). Most patients (67.5%) had no local skin reactions; those occurring were predominantly mild/moderate. Glycopyrronium tosylate efficacy was maintained throughout the trial; at week 44, the Hyperhidrosis Disease Severity Scale responder rate was 63.2%, and improvements from baseline (double blind) in sweat production were -?71.3% and 8.7?±?6.2/6.2?±?4.9 for Dermatology Life Quality Index/children's Dermatology Life Quality Index. CONCLUSIONS:Daily long-term application of glycopyrronium tosylate for up to 48 weeks (double blind plus open label) was generally well tolerated and efficacy was maintained. No new safety signals emerged. TRIAL REGISTRY:Clinicaltrials.gov NCT02553798.
| S-EPMC6687675 | biostudies-literature
Project description:Glycopyrronium tosylate cloth, an anticholinergic drug, has been approved for the topical treatment of primary axillary hyperhidrosis in the USA, but its effects in Japanese patients have not been previously investigated. This 4-week, randomized, double-blind, vehicle-controlled, multicenter study was conducted to evaluate the efficacy and safety of glycopyrronium tosylate cloth for primary axillary hyperhidrosis patients in Japan. Eligible patients, who were ≥9 years of age and had primary axillary hyperhidrosis ≥6 months, with gravimetrically-measured sweat production ≥50 mg/5 min, and Hyperhidrosis Disease Severity Scale ≥3 (moderate) were randomized 1:1:1 to once daily topical glycopyrronium tosylate 3.75%, 2.5%, or vehicle. Overall, 497 patients (163 in the glycopyrronium tosylate 3.75% group, 168 in the glycopyrronium tosylate 2.5% group, and 166 in the vehicle group, hereinafter in this order) were randomized. Statistically higher proportions of patients in the glycopyrronium tosylate groups achieved ≥2-point improvement in Hyperhidrosis Disease Severity Scale and ≥50% reduction in sweat production from baseline versus vehicle at week 4 (51.6%, 41.1%, and 16.4%, respectively; p < 0.001 in both cases). Higher responder rates in the glycopyrronium tosylate groups compared with the vehicle group occurred as early as week 1. The most common treatment-emergent adverse events in patients treated with glycopyrronium tosylate were photophobia, mydriasis, thirst, and dysuria. Most treatment-emergent adverse events were mild as determined by the investigators. The incidence of treatment-emergent adverse events leading to treatment modification was low in the three groups. The 4-week use of topical glycopyrronium tosylate improved the patient-reported outcome measure Hyperhidrosis Disease Severity Scale and objectively-evaluated sweat production with a favorable benefit/risk profile.
| S-EPMC9293301 | biostudies-literature
Project description:BACKGROUND/OBJECTIVES:Glycopyrronium tosylate (GT) cloth, 2.4% is a topical anticholinergic approved in the United States for primary axillary hyperhidrosis in patients ?9 years. This post hoc analysis evaluated long-term response (efficacy and safety) in pediatric patients (?9 to ?16 years) to GT in the 44-week, open-label extension (NCT02553798) of two, phase 3, double-blind, vehicle-controlled, 4-week trials (NCT02530281, NCT02530294). METHODS:In the double-blind trials, patients ?9 years with primary axillary hyperhidrosis were randomized 2:1 to once-daily GT:vehicle. Those who completed the study could receive open-label GT for up to an additional 44 weeks. Safety assessments included treatment-emergent adverse events (TEAEs) and local skin reactions (LSRs). Descriptive efficacy assessments included gravimetrically measured sweat production, Hyperhidrosis Disease Severity Scale response (?2-grade improvement), and Children's Dermatology Life Quality Index. RESULTS:Of 43 pediatric patients completing either double-blind trial, 38 (88.4%) entered the open-label extension (age, years: 9 [n = 1], 12 [n = 2], 13 [n = 7], 14 and 15 [n = 9 each], 16 [n = 10]). The safety profile observed was similar to the double-blind trials. Most TEAEs (>95%) were mild/moderate, related to anticholinergic activity, and infrequently led to discontinuation (n = 1/38 [2.6%]). No pediatric patients experienced a serious TEAE. Most anticholinergic TEAEs did not require a dose modification and resolved within 7 days. Approximately, one-third of patients (n = 13/38 [34.2%]) had LSRs; most were mild/moderate in severity. Improvements in efficacy measures were maintained from the double-blind trials. CONCLUSIONS:Long-term, once-daily GT for up to 48 weeks (4-week double-blind plus 44 week open label) provides a noninvasive, well-tolerated treatment option for pediatric patients with primary axillary hyperhidrosis.
| S-EPMC7383486 | biostudies-literature
Project description:BackgroundGlycopyrronium tosylate (GT) is a topical anticholinergic approved in the USA for primary axillary hyperhidrosis in patients aged ≥ 9 years. GT was evaluated for primary axillary hyperhidrosis in replicate, randomized, double-blind, vehicle-controlled, phase III trials. GT reduced sweating severity and production versus vehicle and was generally well tolerated.ObjectiveOur objective was to evaluate patient-reported outcomes (PROs) from these trials.MethodsPatients aged ≥ 9 years with primary axillary hyperhidrosis ≥ 6 months, gravimetrically measured sweat production ≥ 50 mg/5 min in each axilla, Axillary Sweating Daily Diary (ASDD) Item 2 severity score ≥ 4, and Hyperhidrosis Disease Severity Scale (HDSS) score ≥ 3 were randomized 2:1 to GT 3.75% or vehicle applied once daily to each axilla for 4 weeks. The 4-item ASDD, 6 Weekly Impact (WI) items, Patient Global Impression of Change (PGIC), HDSS, and Dermatology Life Quality Index (DLQI) were utilized.ResultsIn the pooled population, 463 patients were randomized to GT and 234 to vehicle; 426 (92.0%) and 225 (96.2%) completed the trials. At baseline, most patients considered their axillary sweating to be at least moderate in severity, impact, and bothersomeness (ASDD items 2, 3, and 4, respectively). Improvement was substantially greater for GT than for vehicle at every study week, and, at week 4, ASDD scores improved from baseline by 62.6 versus 34.0% (severity), 65.5 versus 40.3% (impact), and 65.4 versus 39.0% (bothersomeness). Improvements favoring GT versus vehicle also occurred for WI items, PGIC, HDSS, and DLQI.ConclusionsPRO results demonstrated that GT reduced the disease burden of primary axillary hyperhidrosis.Trial registrationClinicaltrials.gov; ATMOS-1 (NCT02530281), ATMOS-2 (NCT02530294).
| S-EPMC6516143 | biostudies-literature
Project description:OBJECTIVES:To evaluate the safety, efficacy, and durability of treating axillary hyperhidrosis with high-intensity micro-focused ultrasound plus visualization. DESIGN:Two randomized double-blind, sham-controlled pilot studies. MEASUREMENTS:For Study 1, the primary endpoint was response defined as ?50-percent reduction in baseline sweat production as measured gravimetrically. For Study 2, the primary endpoint was response defined as a reduction of Hyperhidrosis Disease Severity Scale scores from 3 or 4 to 1 or 2. Secondary endpoints included changes in gravimetric and starch-iodine testing and patient satisfaction. RESULTS:In Study 1, ?50 percent of patients achieved a positive treatment response. In Study 2, the response rate at post-treatment Day 60 for micro-focused ultrasound plus visualization- (N=12) and sham-treated (N=8) patients was 67 and zero percent, respectively (p=0.005). Patients evaluated 12 months after treatment (N=11) demonstrated the long-lasting effectiveness of micro-focused ultrasound plus visualization for treating axillary hyperhidrosis. All but one patient in the micro-focused ultrasound plus visualization group were satisfied with their results while all sham group patients were dissatisfied (p=0.0001). Subjective reports of greatest improvement were sweat production (92%) and social embarrassment (83%). Adverse events were found to be mild and were resolved within a short timeframe. CONCLUSION:Micro-focused ultrasound plus visualization appears to be safe, effective, well-tolerated, and a long-lasting means for treating axillary hyperhidrosis.
| S-EPMC3990536 | biostudies-literature
Project description:An extrafine formulation of the long-acting muscarinic antagonist glycopyrronium bromide (GB) is in development for chronic obstructive pulmonary disease (COPD), in combination with beclometasone dipropionate and formoterol fumarate - a "fixed triple". This two-part study was randomized, double blind, placebo controlled in patients with moderate-to-severe COPD: Part 1: single-dose escalation, GB 12.5, 25, 50, 100 or 200 ?g versus placebo; Part 2: repeat-dose (7-day), four-period crossover, GB 12.5, 25 or 50 ?g twice daily (BID) versus placebo, with an open-label extension in which all patients received tiotropium 18 ?g once daily. On the morning of Day 8 in all five periods, patients also received formoterol 12 ?g. In study Part 1, 27 patients were recruited. All GB doses significantly increased from baseline forced expiratory volume in 1 second (FEV1) area under the curve (AUC0-12h) and peak FEV1, with a trend toward greater efficacy with higher GB dose. All adverse events were mild-moderate in severity, with a lower incidence with GB than placebo and no evidence of a dose-response relationship. In study Part 2, of 38 patients recruited, 34 completed the study. Adjusted mean differences from placebo in 12 h trough FEV1 on Day 7 (primary) were 115, 142 and 136 mL for GB 12.5, 25 and 50 ?g BID, respectively (all P<0.001). GB 25 and 50 ?g BID were superior (P<0.05) to GB 12.5 ?g BID for pre-dose morning FEV1 on Day 8. For this endpoint, GB 25 and 50 ?g BID were also superior to tiotropium. Compared with Day 7, addition of formoterol significantly increased Day 8 FEV1 peak and AUC0-12h with all GB doses and placebo (all P<0.001). All adverse events were mild-moderate in severity and there was no indication of a dose-related relationship. This study provides initial evidence on bronchodilation, safety and pharmacokinetics of extrafine GB BID. Overall, the results suggest that GB 25 ?g BID is the optimal dose in patients with COPD.
| S-EPMC5511020 | biostudies-literature
Project description:To evaluate the efficacy and safety of onabotulinumtoxinA in adolescents with primary axillary hyperhidrosis.This 52-week, multicenter, nonrandomized, open-label study was conducted in 141 adolescents ages 12 to 17 years with severe primary axillary hyperhidrosis. Patients could receive up to six treatments with onabotulinumtoxinA (50 U per axilla), with re-treatment occurring no sooner than 8 weeks after the prior treatment cycle and no later than 44 weeks after the initial treatment cycle. The primary efficacy measure was treatment response, based on self-assessed hyperhidrosis severity following the first two treatments using the 4-point Hyperhidrosis Disease Severity Scale (HDSS). Other efficacy measures included spontaneous resting sweat production and health outcomes.Fifty-six (38.9%) participants underwent one treatment, 59 (41.0%) underwent two, 20 (13.9%) underwent three, 6 (4.2%) underwent four, and 3 (2.1%) underwent five. OnabotulinumtoxinA significantly improved HDSS scores and decreased sweat production compared with treatment cycle baselines. Seventy-nine patients (54.9%) responded to treatment based on HDSS criteria. From 56.6% to 72.3% of patients experienced a two-grade or more improvement at 4 and 8 weeks after each of the first two treatments. The majority (79.4%-93.2%) had a 75% or greater reduction in sweat production at week 4 (treatments 1-3). The median duration of effect for responders ranged from 134 to 152 days. Using quality of life measures, health outcomes improved markedly. Eight patients (5.6%) had mild or moderate treatment-related adverse events. No unexpected safety signals were observed in this study. Neutralizing antibodies to onabotulinumtoxinA did not develop.OnabotulinumtoxinA injections provided beneficial effects in adolescents with primary axillary hyperhidrosis.
| S-EPMC4744704 | biostudies-literature
Project description:BACKGROUND:Primary focal axillary hyperhidrosis is a chronic distressing disorder affecting both the sexes. When the condition is refractory to conservative management, we should go for more promising therapies like intradermal botulinum toxin A (BtxA) injections in the axilla, and surgical therapies like subcutaneous curettage of sweat glands. AIMS AND OBJECTIVES:The aim of this study is to compare the efficacy, safety and duration of action of intradermal BtxA injections in one axilla and subcutaneous curettage of sweat glands in the other axilla of the same patient with axillary hyperhidrosis. MATERIALS AND METHODS:Twenty patients (40 axillae) received intradermal BtxA injections on the right side (20 axillae) and underwent tumescent subcutaneous curettage of sweat glands on the left side (20 axillae). Sweat production rate was measured using gravimetry analyses at baseline and at 3 months after the procedure. Subjective analyses were done using hyperhidrosis disease severity scale (HDSS) score at baseline, at 3rd and 6th month after the procedure. RESULTS:At 3 months post-treatment, the resting sweat rate in the toxin group improved by 80.32% versus 79.79% in the subcutaneous curettage method (P = 0.21). Exercise-induced sweat rate in the toxin group improved by 88.76% versus 88.8% in the subcutaneous curettage group (P = 0.9). There was a significant difference in the HDSS score after treatment with both the modalities. There were no adverse events with BtxA treatment compared to very minor adverse events with the surgical method. CONCLUSION:Both intradermal BtxA injections and tumescent subcutaneous curettage of sweat glands had a significant decrease in the sweat rates with no significant difference between the two modalities. Hence, in resource poor settings where affordability of BtxA injection is a constraint, subcutaneous curettage of sweat glands can be preferred which has been found equally effective with no or minimal adverse events.
| S-EPMC5418980 | biostudies-literature
Project description:ImportanceAcne is a common, multifactorial skin condition, and treatments with novel mechanisms have been elusive.ObjectiveTo assess the safety and efficacy of clascoterone cream, 1%, a novel topical androgen receptor inhibitor, in 2 phase 3 randomized clinical trials (CB-03-01/25 and CB-03-01/26).Design, setting, and participantsTwo identical, multicenter, randomized, vehicle-controlled, double-blind, phase 3 studies conducted from November 2015 to April 2018 evaluated the efficacy and safety of use of clascoterone cream, 1%, in males and nonpregnant females 9 years and older with moderate or severe facial acne as scored on the Investigator's Global Assessment scale. Participants were enrolled if they had 30 to 75 inflammatory lesions and 30 to 100 noninflammatory lesions.InterventionsPatients were randomized to treatment with clascoterone cream, 1%, or vehicle cream and applied approximately 1 g to the whole face twice daily for 12 weeks.Main outcomes and measuresTreatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear), and a 2-grade or greater improvement from baseline and absolute change from baseline in noninflammatory and inflammatory lesion counts at week 12. Safety measures included adverse event frequency and severity.ResultsA total of 1440 patients were randomzied in 2 studies. In CB-03-01/25, 353 participants were randomized to treatment with clascoterone cream, 1% (median [range] age, 18.0 [10-58] years; 221 [62.6%] female), and 355 participants were randomized to treatment with vehicle cream (median [range] age, 18.0 [9-50] years; 215 (60.6%) female); in CB-03-01/26, 369 participants were randomized to treatment with clascoterone cream, 1% (median [range] age, 18.0 [10-50] years; 243 [65.9%] female), and 363 participants were randomized to treatment with vehicle cream (median [range] age, 18.0 [range, 11-42] years; 221 [60.9%] female). At week 12, treatment success rates in CB-03-01/25 and CB-03-01/26 with clascoterone cream, 1%, were 18.4% (point estimate, 2.3; 95% CI, 1.4-3.8; P < .001) and 20.3% (point estimate, 3.7; 95% CI, 2.2-6.3; P < .001) vs 9.0% and 6.5% with vehicle, respectively. At week 12, in both CB-03-01/25 and CB-03-01/26, treatment with clascoterone cream, 1%, resulted in a significant reduction in absolute noninflammatory lesions from baseline to -19.4 (point estimate difference, -6.4; 95% CI, -10.3 to -2.6; P < .001) and -19.4 (point estimate difference, -8.6; 95% CI, -12.3 to -4.9; P < .001) vs -13.0 and -10.8 with vehicle, respectively, as well as a reduction in inflammatory lesions from baseline to -19.3 (point estimate difference, -3.8; 95% CI, -6.4 to -1.3; P < .001) and -20.0 (point estimate difference, -7.4; 95% CI, -9.8 to -5.1; P < .001) vs -15.5 and -12.6 with vehicle, respectively. Adverse events rates were low and mostly mild; the predominant local skin reaction was trace or mild erythema.Conclusions and relevanceUse of clascoterone cream, 1%, for acne treatment appears to demonstrate favorable efficacy and safety with low adverse event rates.Trial registrationClinicalTrials.gov Identifiers: NCT02608450 and NCT02608476.
| S-EPMC7177662 | biostudies-literature