Pharmacokinetics of Qbrexza in subjects with renal impairment has not been studied.

In Vitro Studies

In vitro studies indicated that under the conditions of clinical use, Qbrexza is not expected toinduce cytochrome P450 (CYP) enzymes 1A2, 2B6 and 3A4; or inhibit 1A2, 2B6, 2C8, 2C9,

2C19, 2D6 and 3A4.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityGlycopyrronium tosylate was not carcinogenic when topically applied to rats daily for up to24 months in solution at concentrations of 1%, 2%, and 4% w/w.

When glycopyrrolate was administered via oral gavage to mice for up to 24 months at dosagesof 2.5, 7, and 20 mg/kg/day in both genders, no significant changes in tumor incidence were

observed when compared to control.

When glycopyrrolate was administered via oral gavage to rats for up to 24 months at dosages of5, 15, and 40 mg/kg/day in both genders, no significant changes in tumor incidence were

observed when compared to control.

Glycopyrrolate was negative in a battery of genetic toxicology studies that included a bacterialreverse mutation (Ames) assay, a mouse lymphoma assay conducted with L5178Y/TK+/- cells,

and an in vivo micronucleus assay with mice. Glycopyrronium tosylate was negative in an Amesassay.

Glycopyrrolate was assessed for effects on fertility or general reproductive function in rats. 

Ratsof both genders received glycopyrrolate at dosages up to 100 mg/kg/day via oral gavage. Notreatment-related effects on fertility or reproductive parameters were observed in either gender.

14 CLINICAL STUDIES

14.1 Efficacy and Safety Trials

Two randomized, vehicle-controlled multicenter trials, Trial 1 (NCT02530281) and Trial 2(NCT02530294), were conducted in subjects with primary axillary hyperhidrosis and enrolled a

total of 697 subjects 9 years of age or older. Inclusion criteria required that prior to the start oftreatment, all subjects produce at least 50 mg of sweat in each axilla over a 5-minute period and

rate the severity of their sweating daily over a week with a mean score of 4 or higher on the ASDD item #2, a patient reported outcome instrument scored from 0 (no sweating) to 10 (worst

possible sweating). The median sweat production over 5 minutes at baseline was 122 mg in the Qbrexza arm and 113 mg in the vehicle arm in Trial 1, and 127 mg in the Qbrexza arm and

117 mg in the vehicle arm in Trial 2. The average weekly mean score on the ASDD item #2 at baseline was approximately 7.2 across both trials.

Subjects were randomized to receive either Qbrexza or vehicle applied once daily to each axilla.

The co-primary endpoints were the proportion of subjects having at least a 4-point improvementfrom baseline in the weekly mean ASDD item #2 score at Week 4 and the mean absolute

change from baseline in gravimetrically measured sweat production at Week 4. 

Page 9 of 10Clinical Response

The results of Trial 1 and Trial 2 are presented in Table 5 below.

Table 5: Primary Efficacy Outcomes in Subjects with Primary Axillary Hyperhidrosis

Trial 1 Trial 2

Qbrexza,

2.4%

N = 229

Vehicle

N = 115

Qbrexza,

2.4%

N = 234

Vehicle

N = 119

ASDD Item #2 Response at Week 4:

Proportion of subjects with at least a 4-point

improvement from baseline in the weekly

mean ASDD item #2 at Week 4

53% 28% 66% 27%