Evaluation of Testosterone Nasal Gel in Hypogonadal Boys

Study Overview
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Brief Summary
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PK study to evaluate serum levels of testosterone post nasal delivery in two cohorts of hypogonadal boys.

Detailed Description
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ARM 1 - 10 prepubertal, 12-17 years old boys with no prior exposure to TRT will receive single dose of 5.5 mg on day one and single dose of 11 mg on day 2 with repeat blood draws to assess serum levels of testosterone and metabolites. ARM 2 - 10 Tanner Stage 3, 12-17 years old boys on TRT with bone age >= 13 years will receive single dose of 11 mg on day one, and single dose of 11 mg in the morning and a second 11 mg dose in the afternoon on day 2 with repeat blood draws to assess serum levels of testosterone and metabolites.

Official Title
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A Multicenter, Open Label, Variable Dose, Two Arm Pilot Paediatric Phase 1 PK Study to Evaluate Testosterone Nasal Gel (4.5% w/w) in Hypogonadal Boys

Conditions
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Hypogonadism

Intervention / Treatment
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* Drug: Testosterone Nasal Gel [Natesto]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ARM 1 (naïve patients): Participants who meet all of the following inclusion criteria will be eligible for participation in the study: Hypogonadal boys; Chronological age 12 to <18 years; No prior exposure to TRT; Prepubertal Parent/guardian and patient able to understand and provide signed informed consent; ARM 2 (non-naïve patients): Participants who meet all of the following inclusion criteria will be eligible for participation in the study: Hypogonadal boys with a bone age of ≥13 years (a historical value within the last 12 months will be acceptable); Chronological age 12 to <18 years; Taking an existing TRT treatment dose; Tanner Stage ≥3 Parent/guardian and patient able to understand and provide signed informed consent; Exclusion Criteria: ARM 1 (naïve patients) AND ARM 2 (non-naïve patients): Participants who meet any of the following criteria will be excluded from participation in the study: Any active allergic condition or presentation of symptoms including allergic rhinitis; An upper respiratory tract infection; Use of any form of intranasal medication delivery other than periodic short-term (less than 3 days) use of sympathomimetic decongestants, within the last 3 months; In the opinion of the Investigator, significant intercurrent disease of any type, in particular liver, kidney, heart disease, stroke, or psychiatric illness; History of pituitary or hypothalamic tumors or history of any malignancy excluding basal cell or squamous cell carcinoma of the skin curatively treated by surgery; History of nasal disorders, nasal or sinus surgery, nasal fracture within the previous 6 months or nasal fracture that caused a deviated anterior nasal septum surgery, mucosal inflammatory disorders, specifically Sjogren's syndrome; History of severe adverse drug reactions to testosterone therapies; Current treatment with other androgens (e.g., dehydroepiandrosterone [DHEA]), anabolic steroids, or other sex hormones; Treatment with estrogens, gonadotropin-releasing hormone (GnRH) agonists, or growth hormone within the previous 12 months; Treatment with drugs that interfere with the metabolism of testosterone, such as anastrozole, clomiphene, dutasteride, finasteride, flutamide, ketoconazole, spironolactone, or testolactone; Diabetes mellitus; Participation in any other research study during the conduct of this study or 30 days prior to the initiation of this study.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: dual arm: naïve vs TRT experienced
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naive patients - ARM 1<br>TRT naïve subjects, Tanner Stage of 0, receiving Testosterone Nasal Gel [Natesto] - Single dose of 5.5 mg Natesto on Day 1 and a single dose of 11 mg Natesto on Day 2 | Drug: Testosterone Nasal Gel [Natesto]<br>* nasal gel containing 4.5% w/w testosterone<br>|
| Experimental: Non-naive patients - ARM 2<br>TRT non-naïve subjects (have had prior testosterone treatment), Tanner Stage >/= 3, receiving Testosterone Nasal Gel [Natesto] - Single dose of 11 mg Natesto on Day 1. On Day 2, 11 mg dose of Natesto in the morning and 11 mg dose of Natesto 12 hours later | Drug: Testosterone Nasal Gel [Natesto]<br>* nasal gel containing 4.5% w/w testosterone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | Cmax for serum testosterone, serum DHT and serum estradiol | 48 hours (approx) | 
| Area under the curve (AUC) | AUC for serum testosterone, serum DHT and serum estradiol | 48 hours (approx) | 
| Minimum serum concentration (Cmin) | Cmin for serum testosterone, serum DHT and serum estradiol | 48 hours (approx) | 
| Time to reach maximum plasma concentration (tmax) | tmax for serum testosterone, serum DHT and serum estradiol | 48 hours (approx) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (Safety) | Safety assessments will include adverse events, clinical laboratory measurements of serum testosterone, DHT and estradiol levels, and vital sign measurements. A phone call will be made 3 days after the patient leaves the clinic to collect any SAEs or AEs that may occur. | 5 days | 
| Incidence of Treatment-Emergent Adverse Events (Tolerability) | To include a adverse events that relate to tolerability and a patient and healthcare provider questionnaire on ease of use dispenser and gel administration | 48 hours (approx) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paediatric