E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male hypogonadism related to illicit use of anabolic androgenic steroids |
Mandlig hypogonadisme forårsaget af ulovligt af anabole steroider |
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E.1.1.1 | Medical condition in easily understood language |
decreased testicular production and fertility in men caused by illicit use of anabolic steroids |
Svækket egenproduktion af testosteron og fertilitet hos mænd som følge af ulovligt brug af anabole steroider |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
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 | 10058359 |
E.1.2 | Term | 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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021926 |
E.1.2 | Term | Infertility |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast 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 |
The overall objective of this randomized trial is to investigate the effects of treatment of AAS-induced male hypogonadism with combined therapy of letrozole and hCG compared with placebo on reproductive hormone levels |
Hovedformålet med studiet er at undersøge effekten af behandling af mænd med mandlig hypogonadisme som følge af ulovligt brug af anabole androgene steroider med kombinationsbehandling af letrozol of hCG sammenlignet med placebo på parametrene reproduktionshormoner |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: adherence to cessation of AAS use, fertility, cardiac function and quality of life. |
de sekundære formål er afholdenhed fra anabole steroider, fertilitet, hjertefunktion og livskvalitet |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male sex • 18 – 50 years of age • Hypogonadism following observational period of a minimum of 12 weeks since AAS discontinuation or a urine sample negative for AAS analyses at screening visit: plasma total testosterone ≤ 10 nmol/L AND featuring at least one symptom of male hypogonadism using IIEF in terms of erectile function (IIEF: Q1 – Q5 + Q15; total score < 26) and/or sexual desire (IIEF: Q11 + Q12; total < 7) (1) and/or ADAM questionnaire (YES to three questions other than question 1 and 7) and/or regular use of medical treatment for erectile dysfunction.
• Motivation for permanent AAS cessation
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• Male sex • 18 – 50 years of age • Hypogonadism following observational period of a minimum of 12 weeks since AAS discontinuation or a urine sample negative for AAS analyses at screening visit: plasma total testosterone ≤ 10 nmol/L AND featuring at least one symptom of male hypogonadism using IIEF in terms of erectile function (IIEF: Q1 – Q5 + Q15; total score < 26) and/or sexual desire (IIEF: Q11 + Q12; total < 7) (1) and/or ADAM questionnaire (YES to three questions other than question 1 and 7) and/or regular use of medical treatment for erectile dysfunction.
• Motivation for permanent AAS cessation |
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E.4 | Principal exclusion criteria |
• Established cardiovascular disease • Established diabetes of any kind • Congenital hypogonadal conditions (cryptorchidism, Klinefelter’s disease, Kallmann’s disease etc.) • Previous established hypogonadal conditions due to other causes than illicit use of AAS • Current or previous treatment with testosterone on other indication than AAS-induced male hypogonadism • Abnormal puberty development (small testes, late or absent pubic hairing, late or absent deepening of voice, etc.) • Current or previous pituitary diseases • Current or former testicular cancer • Other cancers unless complete remission ≥ 5 year • Other concomitant disease or treatment which according to the investigators’ assessment makes the patient unsuitable to participate in the study • Simultaneous participation in another clinical study • Unable to follow treatment instructions in terms of study medication instructions • Ongoing criminal behavior in terms of violence or illicit distribution of drugs • Currently or in the foreseeable future included in anti-doping programs
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• Established cardiovascular disease • Established diabetes of any kind • Congenital hypogonadal conditions (cryptorchidism, Klinefelter’s disease, Kallmann’s disease etc.) • Previous established hypogonadal conditions due to other causes than illicit use of AAS • Current or previous treatment with testosterone on other indication than AAS-induced male hypogonadism • Abnormal puberty development (small testes, late or absent pubic hairing, late or absent deepening of voice, etc.) • Current or previous pituitary diseases • Current or former testicular cancer • Other cancers unless complete remission ≥ 5 year • Other concomitant disease or treatment which according to the investigators’ assessment makes the patient unsuitable to participate in the study • Simultaneous participation in another clinical study • Unable to follow treatment instructions in terms of study medication instructions • Ongoing criminal behavior in terms of violence or illicit distribution of drugs • Currently or in the foreseeable future included in anti-doping programs
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in plasma total testosterone concentration after 24 weeks from baseline |
ændring i plasma total testosteron concentration efter 24 uger fra start |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 24 weeks |
Efter 24 uger |
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E.5.2 | Secondary end point(s) |
• Group difference in adherence to AAS cessation after 24 and 50 weeks from baseline • Change in total plasma testosterone concentration after 50 weeks from baseline • Change in plasma total testosterone secretion in response to hCG stimulation after 24 and 50 weeks from baseline • Change in basal plasma pituitary gonadotropins, LH and FSH, after 24 and 50 weeks from baseline • Change in secretion of plasma pituitary gonadotropins, LH and FSH, in response to GnRH stimulation after 24 and 50 weeks from baseline • Change in spermatogenesis (sperm count, motility, morphology, sperm acrosome reaction and DNA fragmenting) after 24 and 50 weeks from baseline • Change in testicular size assessed using ultrasound after 24 and 50 weeks • Change in questionnaires scores IIEF (erectile function and libido) and ADAM (hypogonadism) from baseline and after 24 and 50 weeks • Change in questionnaires scores of Major Depression Inventory (MDI) (depression), General Anxiety Disorder 7 (GAD7) (anxiety), Buss-Perry Aggression scale (BPA) (hostility and aggression) and self-administered internet-based Cognition Assessment Tool (ICAT) from baseline and after 24 and 50 weeks • Change in myocardial function assessed by myocardial flow reserve (mL/min/gr) by Rb-82 PET after 24 and 50 weeks from baseline • Change in cardiac systolic function assessed using left ventricular ejection fraction (LVEF) obtained using echocardiography and 24 and 50 weeks from baseline. • Change in cardiac systolic function assessed using left ventricular global longitudinal strain (GLS) obtained using echocardiography and 24 and 50 weeks from baseline. • Change in cardiac structure (left ventricular mass) obtained using echocardiography and 24 and 50 weeks from baseline.
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Group difference in adherence to AAS cessation after 24 and 50 weeks from baseline • Change in total plasma testosterone concentration after 50 weeks from baseline • Change in plasma total testosterone secretion in response to hCG stimulation after 24 and 50 weeks from baseline • Change in basal plasma pituitary gonadotropins, LH and FSH, after 24 and 50 weeks from baseline • Change in secretion of plasma pituitary gonadotropins, LH and FSH, in response to GnRH stimulation after 24 and 50 weeks from baseline • Change in spermatogenesis (sperm count, motility, morphology, sperm acrosome reaction and DNA fragmenting) after 24 and 50 weeks from baseline • Change in testicular size assessed using ultrasound after 24 and 50 weeks • Change in questionnaires scores IIEF (erectile function and libido) and ADAM (hypogonadism) from baseline and after 24 and 50 weeks • Change in questionnaires scores of Major Depression Inventory (MDI) (depression), General Anxiety Disorder 7 (GAD7) (anxiety), Buss-Perry Aggression scale (BPA) (hostility and aggression) and self-administered internet-based Cognition Assessment Tool (ICAT) from baseline and after 24 and 50 weeks • Change in myocardial function assessed by myocardial flow reserve (mL/min/gr) by Rb-82 PET after 24 and 50 weeks from baseline • Change in cardiac systolic function assessed using left ventricular ejection fraction (LVEF) obtained using echocardiography and 24 and 50 weeks from baseline. • Change in cardiac systolic function assessed using left ventricular global longitudinal strain (GLS) obtained using echocardiography and 24 and 50 weeks from baseline. • Change in cardiac structure (left ventricular mass) obtained using echocardiography and 24 and 50 weeks from baseline.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 24 weeks and 50 weeks |
efter henholdsvis 24 uger og 50 uger |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 2 |
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |