A Study to Evaluate Clinical Effect, Pharmacokinetics , Safety, and Tolerability of Umeclidinium in Palmar Hyperhidrosis Subjects
Condition: Hyperhidrosis
MeSH terms: Hyperhidrosis
Intervention: Umeclidinium; Vehicle
Intervention description: Umeclidinium (GSK573719) 1.85% will be supplied as a clear, colourless solution, free from visible particulates, for topical application. Each subject total daily dose will be calculated as per study reference manual (SRM) using subject's hand area. A single dose of study treatment will be based on the size of the subject's hand in order to provide coverage of approximately 2µL/ cm^2. If certain pre-specified criteria for safety and tolerability are met, consideration will be given to decreasing the dose by decreasing the concentration of the topical formulation to 1.15% for the remaining subjects.; The vehicle will be supplied as a clear, colorless solution, free from visible particulates, for topical application.This formulation will be similar to the umeclidinium formulation except that it will be devoid of the umeclidinium parent. A single dose of study treatment will be based on the size of the subject's hand in order to provide coverage of approximately 2µL/ cm^2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Topical; Palmar Hyperhidrosis; Umeclidinium

Summary:

      Umeclidinium (UMEC) is a potent pan-active long-acting muscarinic antagonist (LAMA). It is
      anticipated that topical administration of UMEC will block stimulation of muscarinic
      receptors, thereby reducing the overproduction of sweat in subjects who suffer from
      hyperhidrosis. This study will assess the clinical effect, pharmacokinetics, safety and
      tolerability of topically applied UMEC following once daily topical administration, for 28
      days, to the palms, in subjects with primary palmar hyperhidrosis. The study will also
      investigate if topically applied UMEC, at the highest possible concentration, will decrease
      palmar hyperhidrosis with a systemic anticholinergic adverse event profile similar to or
      below that observed with inhaled administration. This is a double blind (Sponsor unblind),
      repeat dose, randomized, parallel group, placebo controlled study. Study will enrol up to 55
      subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects between 18 and 65 years of age inclusive, at the time of
             signing the informed consent may be considered for enrolment. A female subject is
             eligible to participate if she is not pregnant (as confirmed by a negative urine human
             chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following
             conditions applies:

        Non-reproductive potential defined as, Pre-menopausal females with one of the following:
        Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with
        follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral
        Oophorectomy OR Postmenopausal defined as 12 months of spontaneous amenorrhea [in
        questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and
        estradiol levels consistent with menopause]. Females on hormone replacement therapy (HRT)
        and whose menopausal status is in doubt will be required to use one of the highly effective
        contraception methods if they wish to continue their HRT during the study. Otherwise, they
        must discontinue HRT to allow confirmation of post-menopausal status prior to study
        enrolment.

        Reproductive potential and agrees to follow one of the options listed in the Modified List
        of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential
        (FRP) from 30 days prior to the first dose of study medication and for 30 days after the
        last dose of study medication and completion of the follow-up visit.

        The investigator is responsible for ensuring that subjects understand how to properly use
        these methods of contraception.

          -  The subject has a HDSS score of 3 or 4.

          -  The subject has a diagnosis of primary, palmar hyperhidrosis, defined as excessive,
             palmar sweating of at least 6 months duration without apparent cause and with at least
             one of the following characteristics: Positive family history of hyperhidrosis or
             Hyperhidrosis is bilateral and relatively symmetrical or First episode of
             hyperhidrosis before 25 years of age or Cessation of focal sweating during sleep.

          -  The subject has a Baseline/Day 1 gravimetric assessment of at least 150 mg sweat
             produced at rest, during a period of 5 minutes separately for each palm. (Measurements
             can be repeated up to two times on two different days, screening and/or Baseline/Day 1
             visits, but subjects need to qualify on at least one occasion for each palm.)

          -  The subject agrees to avoid to use nicotine-containing products (including nicotine
             patches) during the treatment period

          -  The subject is capable of giving signed informed consent, which includes compliance
             with the requirements and restrictions listed in the consent form and in protocol

        Exclusion Criteria:

          -  The subject has an unstable or life threatening cardiac disease such as: Myocardial
             infarction or unstable angina in the last 6 months or Unstable or life threatening
             cardiac arrhythmia requiring intervention in the last 3 months or New York Heart
             Association (NYHA) Class IV heart failure

          -  The subject has a diagnosis of Type 1 or Type 2 diabetes, or is receiving treatment
             for control of blood glucose levels.

          -  The subject has a diagnosis of hyperthyroidism, as confirmed by thyroid stimulating
             hormone (TSH), or is receiving treatment for hyperthyroidism.

          -  The subject has a diagnosis of narrow-angle glaucoma, urinary retention, prostatic
             hypertrophy or bladder neck obstruction that in the opinion of the study Investigator
             or Medical Monitor would prevent use of an anticholinergic.

          -  The subject has irritation or active infection of palm area, including sweat glands.

          -  The subject has a current or chronic history of liver disease, or known hepatic or
             biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic
             gallstones that the Investigator deems clinically insignificant)

          -  The subject has an ALT>2xUpper limit of normal (ULN) and bilirubin >1.5xULN (isolated
             bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin
             <35%) at screening.

          -  The subject has QT interval corrected for heart rate (QTc) > 450 milli second (msec)
             or QTc > 480 msec in subjects with Bundle Branch Block.

        The QTc 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 as specified in the Reporting and Analysis Plan (RAP).

          -  The subject has a history of allergy or hypersensitivity to anticholinergic/muscarinic
             receptor antagonist or any ingredient of the preparation.

          -  The subject has had a prior surgical procedure for palmar hyperhidrosis.

          -  The subject has had treatment with radiofrequency and/or microwave devices for palmar
             hyperhidrosis

          -  The subject has had botulinum toxin injections for palmar hyperhidrosis in the last
             year prior to Baseline/Day 1

          -  The subject has had treatment with iontophoresis for palmar hyperhidrosis within 4
             weeks prior to Baseline/Day 1

          -  The subject used antiperspirant on the palms within 2 weeks of the Baseline/Day 1

          -  The subject is a menopausal female who has had symptoms of menopause such as sweating
             or flushing within 3 years of Baseline/Day 1

          -  The subject has used any prohibited medication within the indicated washout period

          -  The subject tested positive for any of the following at screening or within 3 months
             of the first scheduled dose of study medication: Hepatitis B surface antigen (HBsAg)
             and Hepatitis C antibody.

          -  The subject has a positive pre-study drug and/or alcohol test at screening

          -  The subject has 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). This does not apply to UMEC when a
             subject who participated in the 1.85% cohort participates in the 1.15% cohort

          -  The subject has had exposure to more than four investigational medicinal products
             within 12 months prior to the first dosing day.

          -  The subject has any other condition which, in the judgment of the Investigator, would
             put the subject at unacceptable risk from participation in the study (e.g., subjects
             with renal failure).

          -  The subject has clinically significant abnormalities in laboratory values which,
             according to the Investigator, would put the subject at undue risk due to study
             participation.

          -  The subject has abnormal findings on screening ECG deemed clinically significant by
             the Investigator.

          -  The subject is pregnant or lactating or is planning on becoming pregnant during the
             study.