Open-label study to evaluate the safety, local tolerability, systemic exposure, and efficacy of 1% GPB cream in adolescents with severe primary axillary hyperhidrosis

Phase 1

Conditions: Severe primary axillary hyperhidrosis
MedDRA version: 20.0Level: PTClassification code 10020642Term: HyperhidrosisSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2022-000922-46-PL

Lead Sponsor: Dr. August Wolff GmbH & Co. KG Arzneimittel

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 60

Inclusion Criteria

1. Medical diagnosis of severe primary axillary hyperhidrosis with symptoms for at least 3 months before Screening and with a PRHS score of =5 at Screening 2 and Day 1
2. At least 50 mg of sweat production in each axilla measured gravimetrically over a period of 5 minutes at room temperature along with a humidity consistent with the normal climate in that area (patients have to acclimatize to that room for at least 30 minutes before the measurement) at Screening 2
3. Adolescents of both sexes aged 12 to 17 years (until study completion) with a body mass index percentile =10 and =90
4. Local tolerability assessment (skin reaction) score = 0
5. Patient and legal guardians are willing and able to comply with protocol requirements, including blood sample collection
6. Patient and legal guardians are capable of understanding the nature, significance, and implications of the clinical study and to form a rational intention in the light of the facts, voluntarily agree to participation and the study’s provisions, and legal guardians have duly signed the informed consent form

Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Hyperhidrosis-related exclusion criteria:
1. Secondary hyperhidrosis, ie, hyperhidrosis that is secondary to other underlying diseases (such as but not limited to hyperthyroidism, lymphoma, and malaria) or secondary to the use of medication (such as but not limited to antidepressants or sympathomimetics)
2. Previous surgical treatment of hyperhidrosis including sympathectomy, surgical debulking of the sweat glands, subcutaneous tissue curettage, ultrasonic surgery, microwave treatment (miraDry), or laser treatment
3. Botulinum toxin treatment for the treatment of axillary hyperhidrosis in the previous 4 months

Medical history and concomitant disease exclusion criteria:
4. Hypersensitivity to glycopyrronium and its salts (such as glycopyrronium bromide), or to any of the excipients of the investigational medicinal product (IMP)
5. Corrected QT (QTc) >450 msec, or QTc =480 msec in patients with bundle branch block
6. Aspartate aminotransferase and alanine aminotransferase =2 x upper limit of normal (ULN), alkaline phosphatase and bilirubin >1.5 x ULN at Screening (free bilirubin >1.5 × ULN is acceptable if bilirubin fraction test result of direct bilirubin <35% is available)
7. Hashimoto’s disease
8. Active or past neuromuscular disease
9. Glaucoma
10. Active or past acute bleeding with unstable heart and blood circulation status
11. Active chronic inflammatory disease of the large bowel (severe ulcerative colitis)
12. Active or past chronic inflammation of the large bowel complicated by severe extension of the colon (toxic megacolon complicating ulcerative colitis)
13. Active or past blockage of the bowel as a result of paralysis of the bowel muscles (paralytic ileus)
14. Myasthenia gravis
15. Sjögren syndrome
16. Dermal disorders (ie, infections, irritations, or inflammation) in one or both axilla(e)
17. Significant cardiovascular disease
18. Thyrotoxicosis
19. Active or past difficulty in passing urine (successfully treated phimosis is acceptable for study participation)
20. Significant cardiac arrhythmia, such as tachycardiac atrial fibrillation and very frequent extrasystoles
21. Uncontrolled type 1 or type 2 diabetes mellitus
22. Severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m²) or end-stage renal disease requiring dialysis
23. Gilbert’s syndrome
24. Under medical treatment for asthma or severe asthma exacerbation (ie, hospitalization and/or at least 3-day treatment with systemic steroids) within 1 year of Screening
25. Acute or chronic bronchitis
26. Active epilepsy in treatment or past epileptic attack (within 1 year of Screening)
27. Active or past anxiety
28. Active depression (with a Patient Health Questionnaire-9 score >10) or past depression
29. Active hepatitis B or C virus, or HIV-1 or -2 infection (serology test)
30. Active or past alcohol or drug abuse (including abuse of steroids such as, eg, testosterone, methyltestosterone, danazol, or oxandrolone)
31. Any score >1 in the neurological assessment of anticholinergic effects at Screening or Day 1
32. Current treatment with potassium chloride
33. Known disturbed blood-brain barrier (such as patients with recent [within 1 year of Screening] craniocerebral trauma, chemotherapy, radiation therapy, surgery to the skull and brain, or recent intravenous drug users)
34. Psoriasis inversa or psoriasis pustulosa generalisata
35. Any condition or situation that, in the investigator’s opinion, may interfere with the patient’s participation

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The evaluation of the safety, tolerability and systemic exposure (in a subset of patients) of topical administration of 1% GPB in adolescents with severe primary axillary hyperhidrosis.;Secondary Objective: Key secondary objective:<br>The evaluation of the efficacy of topical administration of 1% GPB in adolescents with severe primary axillary hyperhidrosis.;Primary end point(s): Primary endpoints:<br>1. Number of patients with ADRs during treatment<br>2. Number of patients with a local tolerability assessment (skin reaction score) >0 during treatment<br>3. Absolute change in glycopyrronium (GP) plasma concentration from Baseline to Day 15;Timepoint(s) of evaluation of this end point: 1. Baseline to Day 57 until SFU<br>2. Baseline, Day 29, Day 57<br>3. Baseline, Day 8, Day 15

Secondary Outcome Measures

Name	Time	Method

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