A Study to Evaluate Clinical Effect, Pharmacokinetics , Safety, and Tolerability of Umeclidinium in Palmar Hyperhidrosis Subjects

NCT02673619 | Completed Phase 2 Results

• 1 other identifier: 201484
• Study Type: interventional
• Target: 58
• Locations: 2 countries
• Sites: 6

Brief 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.

Conditions

Hyperhidrosis

Keywords

Topical; Palmar Hyperhidrosis; Umeclidinium

Outcome Measures

Primary Outcomes (2)

• Posterior Probability That the Response Rate is Greater Than 50%

  A response rate is defined as percentage of participants who achieved at least 30 percent decrease from Baseline in gravimetric sweat production at Day 29. Baseline was latest assessment prior to first dosing. A response rate of greater than 50 percent was considered to be clinically meaningful (greater than 50 percent of participants achieving at least 30 percent decrease from Baseline in gravimetric sweat production at Day 29). The posterior probability that response rate in sweat production is greater than 50 percent was analyzed. The evaluation was performed using Bayesian analysis, in which latest pre-dose value was used as Baseline.

  Baseline and Day 29

• Percentage of Participants With at Least 30 Percent Reduction From Baseline in Sweat Production at Day 29

  Percentage of participants at Day 29 post-treatment with at least a 30 percent reduction from Baseline in sweat production measured by gravimetry. Participants remained at rest for at least 20-30 min before the measurements in order to reduce external interference. The latest pre-dose value was considered as Baseline value. The summary of percentage of participants from both the cohorts with at least 30 percent reduction from Baseline in sweat production was presented for the average of both palms.

  Baseline and Day 29

Secondary Outcomes (23)

• Percentage of Participants With at Least 50% Reduction From Baseline in Sweat Production at Day 29

  Baseline and Day 29

• Change From Baseline in Amount of Sweat Produced at Day 29

  Baseline and Day 29

• Percentage Change From Baseline/Day1 in Amount of Sweat Produced at Day 29

  Baseline and Day 29

• Number of Participants With Shift of Response in HDSS Score at Day 29

  Baseline and Day 29

• Percentage of Participants With at Least 2-point Decrease From Baseline to Day 29 in HDSS Score

  Baseline and Day 29

Study Arms (2)

Umeclidinium once daily (QD) 1.85%

EXPERIMENTAL

Subjects will apply UMEC topically once daily (2microliter \[µL\]/centimeter \[cm\]\^2) to both the hands (palm and fingers) using graduated syringe at night before bedtime for 28 days. Randomization will be 4:1 (UMEC 1.85%: vehicle)

Drug: Umeclidinium

Vehicle QD

PLACEBO COMPARATOR

subjects will apply vehicle topical once daily (2µL/cm\^2) to both the hands (palm and fingers) using graduated syringe at night before bedtime for 28 days.

Drug: Vehicle

Interventions

Umeclidinium DRUG

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.

Umeclidinium once daily (QD) 1.85%

Vehicle DRUG

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

Vehicle QD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stiefel, a GSK Company: lead
• GlaxoSmithKline: collaborator

Study Sites (6)

GSK Investigational Site

Omaha, Nebraska, 68134, United States

Location

GSK Investigational Site

Raleigh, North Carolina, 27612, United States

Location

GSK Investigational Site

Austin, Texas, 78759, United States

Location

GSK Investigational Site

College Station, Texas, 77845, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Montreal, Quebec, H2K 4L5, Canada

Location

MeSH Terms

Conditions

Hyperhidrosis

Interventions

GSK573719

Condition Hierarchy (Ancestors)

Sweat Gland Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2016
• First Posted: February 4, 2016
• Study Start: March 7, 2016
• Primary Completion: December 8, 2016
• Study Completion: December 8, 2016
• Last Updated: February 9, 2018
• Results First Posted: February 9, 2018

Record last verified: 2018-01

Locations

US (5); CA (1)