Evaluation of Testosterone Nasal Gel in Hypogonadal Boys

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

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

Study Overview

• Status: Terminated
• Conditions: Hypogonadism
• Intervention / Treatment: Drug: Testosterone Nasal Gel [Natesto]

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Matthew Gronski, Ph.D.; Phone Number: 289-334-1461; Email: mgronski@aceruspharma.com
• Study Contact Backup: Name: Nathan Bryson, Ph.D.; Phone Number: 416-679-0776; Email: nbryson@aceruspharma.com

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospital's NHS Foundation Trust
  • Liverpool, United Kingdom, L14 5AB
    • Alder Hey Children's Hospital
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • University of Glasgow, Royal Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

ARM 1 (naïve patients): Participants who meet all of the following inclusion criteria will be eligible for participation in the study:

1. Hypogonadal boys;
2. Chronological age 12 to <18 years;
3. No prior exposure to TRT;
4. Prepubertal
5. 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:

1. Hypogonadal boys with a bone age of ≥13 years (a historical value within the last 12 months will be acceptable);
2. Chronological age 12 to <18 years;
3. Taking an existing TRT treatment dose;
4. Tanner Stage ≥3
5. 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:

1. Any active allergic condition or presentation of symptoms including allergic rhinitis;
2. An upper respiratory tract infection;
3. 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;
4. In the opinion of the Investigator, significant intercurrent disease of any type, in particular liver, kidney, heart disease, stroke, or psychiatric illness;
5. 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;
6. 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;
7. History of severe adverse drug reactions to testosterone therapies;
8. Current treatment with other androgens (e.g., dehydroepiandrosterone [DHEA]), anabolic steroids, or other sex hormones;
9. Treatment with estrogens, gonadotropin-releasing hormone (GnRH) agonists, or growth hormone within the previous 12 months;
10. Treatment with drugs that interfere with the metabolism of testosterone, such as anastrozole, clomiphene, dutasteride, finasteride, flutamide, ketoconazole, spironolactone, or testolactone;
11. Diabetes mellitus;
12. Participation in any other research study during the conduct of this study or 30 days prior to the initiation of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Naive patients - ARM 1; 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]; nasal gel containing 4.5% w/w testosterone
Experimental: Non-naive patients - ARM 2; 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]; nasal gel containing 4.5% w/w testosterone

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Acerus Biopharma Inc.
• Investigators: Principal Investigator: Syed Faisal Ahmed, MD, Royal Hospital for Children, U. of Glasgow

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): April 11, 2020
• Study Completion (Actual): April 11, 2022

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: November 14, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Paediatric
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: NAT-2017-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No