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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2a Study to Evaluate the Clinical Effect, Pharmacokinetics, Safety and Tolerability of Topically Applied Umeclidinium in Subjects With Primary Palmar Hyperhidrosis

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.

Detailed Summary:
Sponsor: Stiefel, a GSK Company

Current Primary Outcome:

  • To assess change from baseline in the posterior probability that the response rate (30% decrease from Baseline in sweat weight, as assessed by gravimetry) is greater than 50% [ Time Frame: Baseline to Day 43 ]
    Sweat production will be measured by gravimetry analysis. The assessment done at baseline or Day 1 will be considered as Baseline value.
  • The proportion of subjects with change in at least 30% reduction from baseline in sweat production at Day 29 [ Time Frame: Baseline and Day 29 ]
    Sweat production will be measured by gravimetry analysis. The assessment done at baseline or Day 1 will be considered as Baseline value.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The proportion of subjects at Day 29 with at least 50% reduction from Baseline/Day1 in sweat production [ Time Frame: Baseline to Day 29 ]
    Subjects will remain at rest for at least 20-30 min before the measurements. Amount of sweat produced will be assessed by gravimetric measurement
  • Change from baseline at Day 29 in amount of sweat produced [ Time Frame: Baseline to Day 29 ]
    Subjects will remain at rest for at least 20-30 min before the measurements. Amount of sweat produced will be assessed by gravimetric measurement
  • Percentage change from baseline at Day 29 in amount in of sweat produced [ Time Frame: Baseline to Day 29 ]
    Subjects will remain at rest for at least 20-30 min before the measurements. Amount of sweat produced will be assessed by gravimetric measurement
  • Change from baseline at Day 29 in Hyperhidrosis Disease Severity Scale (HDSS) score [ Time Frame: Baseline to Day 29 ]
    The HDSS is a 4-point scale ranging from '1' (sweating never noticeable and never interfering with daily activities) to '4' (sweating intolerable and always interfering with daily activities)
  • Proportion of subjects with 2-point decrease from Baseline/Day 1 to Day 29 in HDSS score [ Time Frame: Baseline to Day 29 ]
    HDSS is a 4-point scale ranging from '1' (sweating never noticeable and never interfering with daily activities) to '4' (sweating intolerable and always interfering with daily activities)
  • Plasma concentration after repeat dosing of UMEC [ Time Frame: Day 27 to Day 30 ]
    Plasma samples will be collected Pre dose on Day 27 and 28 and serial samples will be collected on Day 29 at 3hour (h), 6h, 9h, 10h, 12h, 16h, 24h, 36h and 48h post dose
  • Maximum plasma concentration (Cmax) [ Time Frame: Day 27 to Day 30 ]
    Plasma samples will be collected Pre dose on Day 27 and 28 and serial samples will be collected on Day 29 at 3h, 6h, 9h, 10h, 12h, 16h, 24h, 36h and 48h postdose
  • Plasma time of occurrence of Cmax (Tmax) and terminal phase half-life.(t1/2) after repeat dosing of UMEC [ Time Frame: Day 27 to Day 30 ]
    Plasma samples will be collected Pre dose on Day 27 and 28 and serial samples will be collected on Day 29 at 3h, 6h, 9h, 10h, 12h, 16h, 24h, 36h and 48h post dose
  • Plasma terminal elimination rate constant (Lambda z) after repeat dosing of UMEC [ Time Frame: Day 27 to Day 30 ]
    Plasma samples will be collected Pre dose on Day 27 and 28 and serial samples will be collected on Day 29 at 3h, 6h, 9h, 10h, 12h, 16h, 24h, 36h and 48h post dose
  • Plasma area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration [AUC(0-t)] and AUC over the dosing interval [AUC(0-tau)] after repeat dosing of UMEC [ Time Frame: Day 27 to Day 30 ]
    Plasma samples will be collected Pre dose on Day 27 and 28 and serial samples will be collected on Day 29 at 3h, 6h, 9h, 10h, 12h, 16h, 24h, 36h and 48h post dose
  • Plasma pre-dose (trough) concentration at the end of the dosing interval (Ctau) [ Time Frame: Day 27 to Day 30 ]
    Plasma samples will be collected Pre dose on Day 27 and 28 and serial samples will be collected on Day 29 at 3h, 6h, 9h, 10h, 12h, 16h, 24h, 36h and 48h post dose
  • Composite of population pharmacokinetic profile after repeat dosing of UMEC [ Time Frame: Day 27 to Day 30 ]
    After an adequate number of samples are quantifiable, a population PK model will be built to characterize umeclidinium pharmacokinetics following repeated dermal doses. Alternatively, the plasma concentration time data will be used to update the existing model. Analysis will be made by WinNonlin
  • Number of subjects with adverse event (AE) [ Time Frame: Upto Day 43 ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
  • Electrocardiogram (ECG) assessment as a measure of safety and tolerability [ Time Frame: Baseline/Day 1, Day 15 and Day 29 ]
    Single 12-lead ECGs will be obtained using an ECG machine that calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals
  • Change in Hematological parameters assessment as a safety measure [ Time Frame: Baseline/Day 1, Day 15 and Day 29 ]
    Blood samples will be collected to assess platelets counts, red blood cells (RBC), haemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin

    Original Secondary Outcome: Same as current

    Information By: GlaxoSmithKline

    Dates:
    Date Received: January 25, 2016
    Date Started: March 2016
    Date Completion:
    Last Updated: March 21, 2017
    Last Verified: March 2017