GSK1358820 (Botulinum Toxin A) PhIII DB & OL Study in Patients With Axillary Hyperhidrosis

A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study Including an Open-label Phase to Evaluate the Efficacy and Safety of GSK1358820 (Botulinum Toxin Type A) in Patients With Axillary Hyperhidrosis

The primary objective of this study is to demonstrate superiority of single treatment of GSK1358820 (hereinafter, referred to as BOTOX®) over placebo in terms of the efficacy of treatment with BOTOX® 50 U in each axilla (100 U in total for each patient) as intradermal injections based on gravimetric assessment (measurement of spontaneous axillary sweat production) for axillary hyperhidrosis.

Inclusion Criteria:

<At start of the screening phase (Visit 1)>

• At least 50 mg of spontaneous resting axillary sweat production in each axilla measured gravimetrically at room temperature/humidity (20 - 25.6°C/20-80%) over a period of 5 minutes. (Patients should be at rest for at least 30 minutes after physical exercise including walking.)

• Patients with primary axillary hyperhidrosis whose excessive sweating in each axillae interferes daily life activities and whose Hyperhidrosis Disease Severity Scale (HDSS) score is 3 or 4.

• Age of 20 to 75 years at the time of informed consent.

• Both genders are eligible to enrol in the study. For men, only those who can practice contraception during the study period are eligible. Women of childbearing potential may be enrolled only if they have negative pregnancy test both in the screening period and just before treatment. Women of childbearing potential must agree to use one or more of the following reliable contraceptive measures throughout the study period:

  *: Abstinence, oral contraceptives, progesterone injection, levonorgestrel implant, estrogen ring, transdermal contraceptives, intrauterine device, vasectomized partner, and double-barrier contraception (condom or diaphragm with spermicidal jelly/film).

• QTc <450 msec, or QTc <480 msec in patients with bundle branch block. (QTc should be determined on one beat on echocardiogram (ECG) or determined by average on consecutive three beats.)

• Willing and able to provide written informed consent. <At start of the treatment phase (Visit 2)>

• At least 50 mg of spontaneous resting axillary sweat production in each axilla measured gravimetrically at room temperature/humidity (20 - 25.6°C/20-80%) over a period of 5 minutes. (Patients should be at rest for at least 30 minutes after physical exercise including walking.)

• Patients with primary axillary hyperhidrosis whose excessive sweating in each axillae interferes daily life activities and whose HDSS score is 3 or 4.

• Asparate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2 x upper limit of normal (ULN), Alkaline phosphatase (ALP) and bilirubin <= 1.5 x ULN at Visit 1 (Free bilirubin >= 1.5 × ULN will not directly lead to study discontinuation if bilirubin fraction test result of direct bilirubin <35% is available.)

Exclusion Criteria:

<At start of the screening phase (Visit 1)>

• Any systemic neuromuscular junction disorder (e.g., myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis).
• Previous botulinum toxin treatment.
• Expected use of botulinum toxin for the treatment of any other disease during the study period.
• Known allergy to any of the components in the investigational product or iodine.
• Secondary hyperhidrosis, for example, hyperhidrosis that is secondary to other underlying diseases including hyperthyroidism, lymphoma and malaria.
• Previous surgical treatment of hyperhidrosis including sympathectomy, surgical debulking of the sweat glands, subcutaneous tissue curettage and ultrasonic surgery.
• Concurrent use of antibiotics that may interfere with neuromuscular junction function, for example, aminoglycoside antibiotics (e.g., gentamicin sulfate, fradiomycin sulfate), polypeptide antibiotics (e.g., polymixin B sulfate), tetracycline antibiotics, and lincomycin antibiotics, except for those contained in topical antimicrobials.
• Concurrent use of muscle relaxants (e.g., tubocurarin chloride hydrochloride hydrate, dantrolene sodium hydrate) or drugs that may have a muscle relaxant action (e.g. spectinomycin hydrochloride hydrate, antispasmogenics including baclofen, benzodiazepines and benzodiazepine-like drugs, benzamides).
• Chronic respiratory disorder.
• Serious muscle weakness or atrophy.
• Angle closure glaucoma or its precipitation (narrow angle).
• Dermal disorder including infection at anticipated injection sites in either axilla.
• Subject has serious physical symptom(s) (i.e., cardiac / hepatic / renal / hematopoietic disorder). The index of seriousness is Grade 3 of "criteria for classification of seriousness of adverse drug reactions to pharmaceutical products, etc. : Appendix 3" (Pharmaceutical Affairs bureau / Pharmaceutical and Chemical Safety Division (PAB / PSD) Notification No.80 in 1992).
• Anticipated need for surgery or hospitalization during the study period.
• Women who are pregnant, lactating, possibly pregnant or planning a pregnancy during the study period.
• Participation in another clinical study within 6 months of study entry or planned participation in another clinical study after entry to this study.
• Psychiatry disorder or cognitive disorder that may affect the patient's ability to give informed consent or to follow specified study procedures.
• History of alcohol or drug abuse.
• Any condition or situation that, in the investigator's or subinvestigator's opinion, may interfere with the patient's participation in the study.

<At start of the treatment phase (Visit 2)>

• Use of cholinomimetics, anticholinergics, antiperspirants containing aluminum chloride and deodorants, any oral herbal medicine treatments or any other topical treatments for hyperhidrosis within 7 days prior to study treatment..
• Underarm hair removed within 12 hours prior to study treatment or not removed sufficiently.
• Any condition or situation that, in the investigator's or subinvestigator's opinion, may interfere with the patient's participation in the study.