Hyperhidrosis
Conditions
Brief summary
The purpose of the study is to assess the safety of 2 doses of glycopyrrolate compared to 2 doses of glycopyrronium and vehicle (5 treatment arms) for the treatment of axillary hyperhidrosis when applied once daily for 4 weeks followed by a 2-week post-dose period.
Detailed description
This is a randomized, double-blind, vehicle controlled, parallel group, comparator study designed to assess the safety, efficacy and pharmacokinetics of two doses of glycopyrrolate compared to two doses of glycopyrronium compared to vehicle, 5 treatment arms. Efficacy will be assessed through gravimetric assessment of sweat production using Patient Reported Outcome and the Hyperhidrosis Disease Severity Score (HDSS). Safety will be assessed through adverse events, local skin responses, serum chemistry and hematology laboratory testing, ECGs, physical examination and vital signs. PK blood samples will be taken study subjects.
Interventions
DRUGDose 1 of glycopyrrolate, 2.0% QD
Dose 1 of glycopyrrolate Topical Wipes
DRUGDose 2 of glycopyrrolate, 3.0% QD
Dose 2 of glycopyrrolate Topical Wipes
DRUGDose 1 of glycopyrronium, 2.5% QD
Dose 1 of glycopyrronium Topical Wipes
DRUGDose 2 of glycopyrronium, 3.75% QD
Dose 2 of glycopyrronium Topical Wipes
OTHERVehicle
Vehicle Topical Wipes
Sponsors
Journey Medical Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, 18 years of age or older. * Primary, axillary hyperhidrosis of at least 6 months duration. * Hyperhidrosis Disease Severity Score (HDSS) of 3 or 4 at baseline. * For each axilla, a baseline gravimetric measurement of sweat production of at least 50 mg over 5 minutes, while at rest, at room temperature. * Male or non-pregnant, non-lactating females.
Exclusion criteria
* Current pregnancy or lactation. * Prior surgical procedure for hyperhidrosis. * Any prior axillary treatment with an anti-hyperhidrosis medical device * Any prior treatment with an investigational drug within 4 weeks prior to Baseline/Day 1 or within 5 elimination half lives of the active agent, whichever is longer or 6 weeks if the elimination half life is not known. Experimental devices are excluded without the approval of the Medical Monitor. * Prior treatment with botulinum toxin (e.g., Botox®) for axillary hyperhidrosis within 1 year of Baseline/Day 1. * Subjects with clinically significant abnormalities in laboratory values. * Subjects with a positive Hepatitis or HIV.Hepatitis B surface antibody positive is allowed only if the subject has a history of having received Hepatitis B vaccination and there are no clinically significant abnormalities in screening liver function tests. * Treatment with cholinergic, serotonergic antagonists, and dopamine partial agonists thought to relieve antidepressant-induced hyperhidrosis, within one month prior to Baseline/Day 1. * Treatment with psychotherapeutic medications for less than 4 months prior to Baseline/Day 1. * Treatment with topical or systemic anticholinergics, adrenergic agonists (clonidine), or beta-blockers within 4 weeks of the baseline visit * Prior treatment with axillary iontophoresis within 4 weeks of Baseline/Day 1. * Any previous IV or oral treatment with the study drug. * Prior treatment with the topical study drug in a previous trial. * Axillary use of nonprescription or prescription antiperspirants within 2 weeks of study enrollment. * Presence of a condition, within 10 years of enrollment, that may cause secondary hyperhidrosis * Menopausal women who have had symptoms of menopause such as sweating or flushing within 3 years of the study may not be enrolled. * Known history of Sjögren's syndrome or Sicca syndrome. * History of glaucoma, inflammatory bowel disease, toxic megacolon, or febrile illness. * Men with a history of urinary retention requiring catheterization due to prostatic hypertrophy or severe obstructive symptoms of prostatic hypertrophy. * Abnormal findings on screening ECG deemed clinically significant by the Investigator. * History or presence of ventricular arrhythmias, atrial fibrillation, atrial flutter. History of other supraventricular tachycardia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 4 | Baseline - Week 4 | — |
| Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 4 | Baseline - Week 4 | Subjects are acclimated to the environment for 30 minutes. Dry gauze is weighed. The dry gauze is then applied to the subject's axilla with the arm down by the subject's side or on their lap during the 5-minute period of sweat production. The gauze with the sweat is then weighed. The difference between the Weight of the gauze with sweat and the dry gauze is the gravimetric sweat measurement in mg/5min. |
| Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 6 | Baseline - Week 6 | — |
| Percentage of Subjects Who Have a Minimum 2-grade Improvement in HDSS From Baseline at Week 4 | Baseline - Week 4/ET | HDSS is a disease specific diagnostic tool that provides a qualitative measure of the severity of the subjects' condition based on how it affects daily activities. 1 (Best), 2, 3, 4 (Worst) |
| Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 6 | Baseline - Week 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 4 | Baseline - Week 4 |
| Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 6 | Baseline - Week 6 |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose 1 of Glycopyrrolate Dose 1 of glycopyrrolate Topical Wipes | 21 |
| Dose 2 of Glycopyrrolate Dose 2 of glycopyrrolate Topical Wipes | 20 |
| Dose 1 of Glycopyrronium Dose 1 of glycopyrronium Topical Wipes | 22 |
| Dose 2 of Glycopyrronium Dose 2 of glycopyrronium Topical Wipes | 20 |
| Vehicle Vehicle Topical Wipes | 22 |
| Total | 105 |
Baseline characteristics
| Characteristic | Dose 1 of Glycopyrrolate | Dose 2 of Glycopyrrolate | Dose 1 of Glycopyrronium | Dose 2 of Glycopyrronium | Vehicle | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 5 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 19 Participants | 21 Participants | 16 Participants | 22 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 19 Participants | 19 Participants | 20 Participants | 22 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 20 Participants | 16 Participants | 17 Participants | 20 Participants | 91 Participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 7 Participants | 13 Participants | 13 Participants | 48 Participants |
| Sex: Female, Male Male | 13 Participants | 13 Participants | 15 Participants | 7 Participants | 9 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 20 | 0 / 22 | 0 / 20 | 0 / 21 |
| other Total, other adverse events | 4 / 21 | 8 / 20 | 11 / 22 | 10 / 20 | 6 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 | 0 / 22 | 0 / 20 | 0 / 21 |
Outcome results
Primary
Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 4
Subjects are acclimated to the environment for 30 minutes. Dry gauze is weighed. The dry gauze is then applied to the subject's axilla with the arm down by the subject's side or on their lap during the 5-minute period of sweat production. The gauze with the sweat is then weighed. The difference between the Weight of the gauze with sweat and the dry gauze is the gravimetric sweat measurement in mg/5min.
Time frame: Baseline - Week 4
Population: Participant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose 1 of Glycopyrrolate | Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 4 | -104.20 mg/5 min | Standard Deviation 73.73 |
| Dose 2 of Glycopyrrolate | Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 4 | -58.27 mg/5 min | Standard Deviation 31 |
| Dose 1 of Glycopyrronium | Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 4 | -105.28 mg/5 min | Standard Deviation 95.83 |
| Dose 2 of Glycopyrronium | Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 4 | -72.69 mg/5 min | Standard Deviation 82.48 |
| Vehicle | Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 4 | -53.85 mg/5 min | Standard Deviation 70.65 |
Primary
Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 6
Time frame: Baseline - Week 6
Population: Participant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose 1 of Glycopyrrolate | Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 6 | -92.20 mg/5 min | Standard Deviation 74.87 |
| Dose 2 of Glycopyrrolate | Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 6 | -44.37 mg/5 min | Standard Deviation 40.92 |
| Dose 1 of Glycopyrronium | Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 6 | -96.98 mg/5 min | Standard Deviation 103.38 |
| Dose 2 of Glycopyrronium | Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 6 | -66.17 mg/5 min | Standard Deviation 78.96 |
| Vehicle | Absolute Change in the Gravimetrically Measured Sweat Production From Baseline to Week 6 | -71.06 mg/5 min | Standard Deviation 64.82 |
Primary
Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 4
Time frame: Baseline - Week 4
Population: Participant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose 1 of Glycopyrrolate | Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 4 | 16 Participants |
| Dose 2 of Glycopyrrolate | Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 4 | 17 Participants |
| Dose 1 of Glycopyrronium | Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 4 | 15 Participants |
| Dose 2 of Glycopyrronium | Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 4 | 14 Participants |
| Vehicle | Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 4 | 12 Participants |
Primary
Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 6
Time frame: Baseline - Week 6
Population: Participant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose 1 of Glycopyrrolate | Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 6 | 19 Participants |
| Dose 2 of Glycopyrrolate | Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 6 | 16 Participants |
| Dose 1 of Glycopyrronium | Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 6 | 17 Participants |
| Dose 2 of Glycopyrronium | Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 6 | 13 Participants |
| Vehicle | Percentage of Subjects Who Have a Minimum 1-grade Improvement in HDSS From Baseline at Week 6 | 13 Participants |
Primary
Percentage of Subjects Who Have a Minimum 2-grade Improvement in HDSS From Baseline at Week 4
HDSS is a disease specific diagnostic tool that provides a qualitative measure of the severity of the subjects' condition based on how it affects daily activities. 1 (Best), 2, 3, 4 (Worst)
Time frame: Baseline - Week 4/ET
Population: Participant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose 1 of Glycopyrrolate | Percentage of Subjects Who Have a Minimum 2-grade Improvement in HDSS From Baseline at Week 4 | 10 Participants |
| Dose 2 of Glycopyrrolate | Percentage of Subjects Who Have a Minimum 2-grade Improvement in HDSS From Baseline at Week 4 | 10 Participants |
| Dose 1 of Glycopyrronium | Percentage of Subjects Who Have a Minimum 2-grade Improvement in HDSS From Baseline at Week 4 | 9 Participants |
| Dose 2 of Glycopyrronium | Percentage of Subjects Who Have a Minimum 2-grade Improvement in HDSS From Baseline at Week 4 | 10 Participants |
| Vehicle | Percentage of Subjects Who Have a Minimum 2-grade Improvement in HDSS From Baseline at Week 4 | 6 Participants |
Secondary
Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 4
Time frame: Baseline - Week 4
Population: Participant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose 1 of Glycopyrrolate | Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 4 | 19 Participants |
| Dose 2 of Glycopyrrolate | Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 4 | 16 Participants |
| Dose 1 of Glycopyrronium | Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 4 | 20 Participants |
| Dose 2 of Glycopyrronium | Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 4 | 16 Participants |
| Vehicle | Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 4 | 15 Participants |
Secondary
Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 6
Time frame: Baseline - Week 6
Population: Participant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose 1 of Glycopyrrolate | Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 6 | 15 Participants |
| Dose 2 of Glycopyrrolate | Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 6 | 15 Participants |
| Dose 1 of Glycopyrronium | Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 6 | 17 Participants |
| Dose 2 of Glycopyrronium | Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 6 | 16 Participants |
| Vehicle | Percentage of Subjects Who Had at Least 50% Reduction in Gravimetrically Measured Sweat Production From Baseline at Week 6 | 14 Participants |