Pharmacokinetic, Safety, Tolerability, and Clinical Effect of Topical Umeclidinium in Primary Axillary Hyperhidrosis

Inclusion Criteria

• Between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• A Hyperhidrosis Disease Severity Scale (HDSS) score of 3 or 4.
• A diagnosis of primary, axillary hyperhidrosis, defined as excessive, bilateral, axillary sweating of at least 6 months duration without apparent cause and with at least 1 of the following characteristics: subject has a positive family history of hyperhidrosis, hyperhidrosis is bilateral and relatively symmetrical, subject experienced first episode of hyperhidrosis before 25 years of age, subject experiences cessation of focal sweating during sleep.
• A baseline gravimetric assessment of at least 50 milligrams sweat produced at rest by each axilla during a period of 5 minutes (measurements can be repeated up to 2 times on two different days, screening and baseline visits, but subjects need to qualify on at least one occasion).
• Male.
• A female is eligible to enter and participate in the study if she is of:

Non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, > 45 years, in the absence of hormone replacement therapy. In questionable cases for women 2 x Upper Limit of Normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 450 milliseconds (ms) or QTc > 480 ms in subjects with Bundle Branch Block.

The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read.

The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.

For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used.

• Prior surgical procedure for hyperhidrosis.
• Axillary treatment with radiofrequency and microwave devices.
• Treatment with axillary iontophoresis within 4 weeks prior to Baseline/Day 1.
• Menopausal women who have had symptoms of menopause such as sweating or flushing within 3 years of the study.
• Used any prohibited medication within the indicated washout period.
• Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, sympathomimetic.
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
• A positive pre-study drug/alcohol screen at screening.
• A positive test for Human Immunodeficiency Virus (HIV) antibody at screening.
• The subject has participated in a clinical trial and has received an investigational product within the following time periods prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
• Any other condition which, in the judgment of the investigator, would put the subject at unacceptable risk for participation in the study (e.g., subjects with renal failure).
• Subjects with clinically significant abnormalities in laboratory values for which, according to the investigator, study participation would put the subject at undue risk.
• Abnormal findings on screening electro