In patients 9 years and older
RAPID EFFICACY DEMONSTRATED ACROSS TWO PHASE 3 MULTICENTER TRIALS1,2
Phase 3 pivotal trial design
Two randomized, vehicle-controlled Phase 3 trials, ATMOS-1 and ATMOS-2, enrolled a total of 697 patients 9 years of age or older with primary axillary hyperhidrosis1,2
Endpoints at Week 4:
- Sweat severity: ASDD and ASDD-C (child-specific) Item 2 responder
- – ASDD Item 2: During the past 24 hours, how would you rate your underarm sweating at its worst? 10 (worst possible sweating) to 0 (no sweating at all)
- – ASDD-C Item 2: Thinking about last night and today, how bad was your underarm sweating? 10 (worst possible sweating) to 0 (no sweating at all)
- – A novel validated patient-reported outcome tool developed in consultation with the FDA2
ASDD/ASDD-C (child-specific) Item 2=Axillary Sweating Daily Diary Item 2.
Key trial inclusion criteria
Selected inclusion criteria for ATMOS-1 and ATMOS-21,2
- ≥9 years of age
- Primary axillary hyperhidrosis for ≥6 months
- Gravimetrically measured sweat production of ≥50 mg/5 min in each axilla
- ASDD Item 2 sweat severity score ≥4 points
- Hyperhidrosis Disease Severity Scale (HDSS) ≥3†
†HDSS is a 4-point scale (patient-reported outcome) that measures the severity of sweating based on tolerability and impact on daily activities.3
Patient demographics and baseline disease characteristics were similar across treatment arms in ATMOS-1 and ATMOS-22,4,5
Coprimary endpoint 1: sweat severity (ASDD Item 2)
60% of patients using QBREXZA reported a ≥4-point
sweat severity score on an 11-point scale at Week 42‡
‡Mean ASDD Item 2 score was 7.3 at
§Mean ASDD Item 2 score was 7.2 at baseline.2
During the past 24 hours, how would you rate your underarm sweating at its worst? Worst possible sweating (10) to no sweating at all (0).
IMPORTANT SAFETY INFORMATION (continued)
Contraindications: QBREXZA is contraindicated in patients with medical conditions that can be exacerbated by the anticholinergic effect of QBREXZA (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis, Sjogren’s syndrome).
Contraindications: QBREXZA is contraindicated in patients with medical conditions that can be exacerbated by the anticholinergic effect of Qbrexza (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis, Sjogren’s syndrome).
Trial-specific sweat severity results (ASDD Item 2)
Significantly more patients using QBREXZA reported a
improvement in sweat severity from baseline1,2
About sweat severity scoring (ASDD Item 2)
A ≥4-point improvement in ASDD Item 2 response corresponds with at least "moderately better" patient-reported improvement in sweating at Week 42
¶The change in mean ASDD Item 2 score from baseline to Week 4 for patients using alcohol-based vehicle was 2.5 points (baseline mean score was 7.2).4
What is ASDD Item 2?
A novel validated patient-reported outcome tool developed in consultation with the FDA to measure sweat severity.2
- ASDD was used to assess sweat severity
- ASDD Item 2 was developed in consultation with the FDA and the 2009 FDA guidance on patient-reported outcomes
- ASDD-C was developed for patients younger than 16
How ASDD Item 2 was measured
Patients were first asked whether they had experienced any underarm sweating in the last 24 hours
- Patients who answered "Yes" were then asked to rate that sweat:
- ASDD: During the past 24 hours, how would you rate your underarm sweating at its worst?
- ASDD-C: Thinking about last night and today, how bad was your underarm sweating?
- Results reported as the proportion of patients with ≥4-point improvement in sweating severity from baseline on an 11-point scale from 10 (worst possible sweating) to 0 (no sweating at all)
Coprimary endpoint 2: sweat production (measured gravimetrically)
74% reduction in median sweat production with QBREXZA at Week 44
#Quartile values range at Week 4: QBREXZA = 15.30 to 75.02; alcohol-based vehicle = 33.84 to 105.92.
WARNINGS AND PRECAUTIONS
Worsening of Urinary Retention: QBREXZA should be used with caution in patients with a history or presence of documented urinary retention. Prescribers and patients should be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, distended bladder), especially in patients with prostatic hypertrophy or bladder-neck obstruction. Instruct patients to discontinue use immediately and consult a physician should any of these signs or symptoms develop. Patients with a history of urinary retention were not included in the clinical studies.
*Quartile values range at Week 4: QBREXZA= 15.30 to 75.02; alcohol-based vehicle = 33.84 to 105.92.
WARNINGS AND PRECAUTIONS
Reduction in sweat production measured gravimetrically—by trial
Greater decrease in median sweat production with QBREXZA1
Gravimetric measurement of sweat production
The absolute change in axillary sweat production measured
gravimetrically was a coprimary endpoint of ATMOS-1 and
- Sweat production was measured per mg/5 min in each axilla
- Two gauze pads were applied to dried axillary surface for 5 minutes
- Gauze was removed and weighed to quantify sweat production
Exploratory endpoint: Patient Global Impression of Change
In patients aged 16 years and older who completed the Patient Global Impression of Change
MOST PATIENTS (77%) REPORTED DAILY TREATMENT WITH QBREXZA IMPROVED THEIR SWEATING6
Overall, how would you rate your underarm sweating now as compared to before starting the study treatment? 1 (much better), 2 (moderately better), 3 (a little better),4 (no difference), 5 (a little worse), 6 (moderately worse), 7 (much worse).
WARNINGS AND PRECAUTIONS (continued)
Control of Body Temperature: In the presence of high ambient temperature, heat illness (hyperpyrexia and heat stroke due to decreased sweating) can occur with the use of anticholinergic drugs such as QBREXZA. Advise patients using QBREXZA to watch for generalized lack of sweating when in hot or very warm environmental temperatures and to avoid use if not sweating under these conditions.
PGIC was an additional exploratory patient-reported outcome
endpoint in ATMOS-1 and ATMOS-22
- Patient rating of axillary sweating after 4 weeks of daily treatment
- Assesses the overall impact of treatment on sweating compared to before the study
- Qbrexza. Package insert. Dermira, Inc; 2018.
- Glaser DA, Hebert AA, Nast A, et al. Topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: results from the ATMOS-1 and ATMOS-2 phase 3 randomized controlled trials. J Am Acad Dermatol. 2019;80(1):128-138.
- Solish N, Bertucci V, Dansereau A, et al; for the Canadian Hyperhidrosis Advisory Committee. A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: recommendations of the Canadian Hyperhidrosis Advisory Committee. Dermatol Surg. 2007;33(8):908-923.
- Data on file. Dermira, Inc. Menlo Park, CA.
- Hebert AA, Glaser DA, Green L, et al. Glycopyrronium tosylate in pediatric primary axillary hyperhidrosis: Post hoc analysis of efficacy and safety findings by age from two phase three randomized controlled trials. Pediatr Dermatol. 2019;36:89-99.
- Pariser DM, Hebert AA, Drew J, Quiring J, Gopalan R, Glaser DA. Topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: patient‑reported outcomes from the ATMOS‑1 and ATMOS‑2 phase III randomized controlled trials. Am J Acad Dermatol. 2019;20(1):135-145.
The most common adverse reactions seen in ≥2% of subjects treated with QBREXZA were dry mouth (24.2%), mydriasis (6.8%), oropharyngeal pain (5.7%), headache (5.0%), urinary hesitation (3.5%), vision blurred (3.5%), nasal dryness (2.6%), dry throat (2.6%), dry eye (2.4%), dry skin (2.2%) and constipation (2.0%). Local skin reactions, including erythema (17.0%), burning/stinging (14.1%) and pruritus (8.1%) were also common.DRUG INTERACTIONS
Anticholinergics: Coadministration of QBREXZA with anticholinergic medications may result in additive interaction leading to an increase in anticholinergic adverse effects. Avoid coadministration of QBREXZA with other anticholinergic-containing drugs.INSTRUCTIONS FOR ADMINISTERING QBREXZA
Instruct patients to use one cloth to apply QBREXZA to both axillae by wiping the cloth across one underarm, ONE TIME. Using the same cloth, apply the medication to the other underarm, ONE TIME. Inform patients that QBREXZA can cause temporary dilation of the pupils and blurred vision if it comes in contact with the eyes.
Instruct patients to wash their hands with soap and water immediately after discarding the used cloth.USE IN SPECIFIC POPULATIONS
Pregnancy: There are no available data on QBREXZA use in pregnant women to inform a drug-associated risk for adverse developmental outcomes.
Lactation: There are no data on the presence of glycopyrrolate or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for QBREXZA and any potential adverse effects on the breastfed infant from QBREXZA or from the underlying maternal condition.
Renal Impairment: The elimination of glycopyrronium is severely impaired in patients with renal failure.