E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary and secondary hypogonadism |
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E.1.1.1 | Medical condition in easily understood language |
Primary and secondary hypogonadism |
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E.1.1.2 | Therapeutic area | Body processes [G] - Biological Phenomena [G16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052649 |
E.1.2 | Term | Primary hypogonadism |
E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059594 |
E.1.2 | Term | Secondary hypogonadism |
E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the PK profile of serum testosterone, serum dihydrotestosterone and serum estradiol [AUC, Cavg, Cmin, Cmax, and tmax] after treatment with variable doses of Testosterone Nasal Gel 4.5% w/w (NATESTO™) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the following:
• Safety monitoring;
• Acceptability of gel will be assessed using questionnaires to determine:
o Tolerability
o Ease of administration
o Patient preference (for non-naïve patients)
o Investigator assessment of use of nasal gel product
o Assessment of dose delivery/deposition relative to paediatric nasal anatomy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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. Any active malignancy, however a prior history of a malignancy which has been in remission for 12 months will be allowed;
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 drugs that interfere with the metabolism of testosterone, such as anastrozole, clomiphene, dutasteride, finasteride, flutamide, ketoconazole, spironolactone, or testolactone;
10. Diabetes mellitus;
11. Participation in any other research study during the conduct of this study or 30 days prior to the initiation of this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic parameters for total serum testosterone, serum dihydrotestosterone and serum estradiol including AUC, Cavg, Cmin, Cmax and Tmax, using 9 samples per participant taken predose and up to 12 hours post each dose. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Data from blood draws at the following time points will be used to calculate the PK parameters listed as the primary end points:
• Naïve patients: 0, 20 min, 40 min, 60 min (±2 min), 90 min, 2 h, 4 h, 8 h, 12 h (±5 min) on both Day 1 and Day 2.
• Non-naïve patients: 0, 20 min, 40 min, 60 min (±2 min), 90 min, 2 h, 4 h, 8 h, 12 h (±5 min) on Day 1 and 0, 20 min, 40 min, 60 min (±2 min), 90 min, 2 h, 4 h, 8 h, 12 h (±5 min) after both doses on Day 2.
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E.5.2 | Secondary end point(s) |
• Safety and tolerability assessments
• Acceptability assessments
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluated up to 36 hours for naïve patients and 48 hours for non naïve patients. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
PK evaluation, safety & tolerability in paediatric population as per PDCO Decision & Protocol |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |