| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Male hypogonadism |
| Hipogonadismo |
|
| E.1.1.1 | Medical condition in easily understood language |
| Low testosterone levels in men. |
| Hombre con bajos niveles de testosterona |
|
| 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 | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10021011 |
| E.1.2 | Term | Hypogonadism male |
| E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
| 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 primary objective of the double blind phase is to compare the effect of testosterone solution vs. placebo on the proportion of hypogonadal men having a serum total testosterone concentration within the normal range (300 ? 1050 ng/dL) at the completion of 12 weeks of treatment.
The primary objective of the open-label extension phase is to assess the safety of testosterone solution for an additional 24 weeks in hypogonadal men using the following measures:
? Adverse events
? Clinical laboratory tests (including hematocrit)
? Prostate safety (prostate specific antigen [PSA] and digital rectal exam)
? International Prostate Symptom Score (IPSS) |
| El objetivo principal de este estudio es comparar el efecto de la solución de testosterona con el de placebo, en relación con la proporción de varones con hipogonadismo que presenten una concentración sérica total de testosterona dentro de la normalidad (300 ? 1050 ng/dl), una vez que hayan completado 12 semanas de tratamiento. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the double-blind phase are:
a) In patients with low sex drive, assess and compare the impact of testosterone solution vs. placebo on levels of sexual arousal, interest, and drive, as measured by change from baseline in scores on the Sexual Arousal, Interest, and Drive (SAID) Scale.
b) In patients with low energy, assess and compare the impact of testosterone solution vs. placebo on levels of energy as measured by change from baseline in scores on the Hypogonadism Energy Diary (HED). |
? En pacientes con poco deseo sexual, evaluar y comparar el efecto de la solución de testosterona y de placebo, en relación con la estimulación, el interés y el deseo sexual, de acuerdo con la variación observada respecto a la puntuación basal en la Escala de Excitación, Interés y Deseo Sexual (SAID).
? En pacientes con poca energía, evaluar y comparar el efecto de la solución de testosterona y de placebo, en relación con el grado de energía, de acuerdo con la variación observada respecto a la puntuación basal en el Diario de Energía en el Hipogonadismo (HED). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Able to read, understand, and provide signed informed consent before starting trial activities related to Study TSAT (including discontinuing [washout] testosterone replacement therapy or other therapies prior screening).
[2] Male at least 18 years of age at the time of screening.
[3] Total testosterone level <300ng/dL (10.4 nmol/L) obtained at each of the 2 screening visits, performed at least 1 week apart (morning lab collection required between 0700 and 1100 hours).
[4] Currently have at least 1 symptom of testosterone deficiency, which must include decreased energy or decreased sexual drive, based on patient reported history and opinion of the investigator.
[5] If the individual is taking lipid-lowering medications, insulin, antidepressants, anxiolytics, or therapy for benign prostatic hyperplasia (BPH), their dose must be stable for at least 3 months prior to screening in the opinion of the investigator.
[6] PSA <4 ng/ml at the time of screening.
[7] Agree to not start any new medication for erectile dysfunction (ED) or libido during the study at any point from screening to the end of the double-blind portion of the study (including herbal and over-the-counter medications).
[8] If the individual is receiving testosterone replacement therapy and is willing to discontinue testosterone replacement therapy to enter the study, their screening testosterone level cannot be checked until at least 14 days after discontinuing oral or topical therapies (or at least 30 days for patients using short-acting intramuscular [IM] therapies [testosterone cypionate or testosterone enanthate] or at least 6 months for patients using long-acting IM testosterone undecanoate). |
[1] Ser capaz de leer, comprender y proporcionar el consentimiento informado firmado antes de realizar cualquiera de las actividades del estudio TSAT (incluida la interrupción [reposo farmacológico] del tratamiento de restitución con testosterona o de otros tratamientos antes de la visita 1).
[2] Varones que en la visita 1 tengan al menos 18 años de edad.
[3] Presentar una concentración total de testosterona < 300 ng/dl (10,4 nmol/l) en cada una de las 2 visitas de selección (visita 1 y visita 2), entre las cuales deberá haber transcurrido al menos 1 semana (la extracción matutina de las muestras debe realizarse entre las 0700 y las 1100 horas).
[4] Presentar en la actualidad al menos 1 síntoma indicativo de carencia de testosterona (entre los que deberán incluirse una menor energía o un menor deseo sexual), basándose en los antecedentes notificados por el paciente y la opinión del investigador.
[5] En caso de que el individuo esté tomando hipolipemiantes, insulina, antidepresivos, anxiolíticos o tratamiento para la hiperplasia prostática benigna (HPB), deberá haber recibido una dosis estable al menos durante los 3 meses previos a la visita 1 (de acuerdo con el criterio del investigador).
[6] Presentar una concentración de PSA < 4 ng/ml en la visita 2.
[7] Estar de acuerdo en no comenzar a tomar ninguna nueva medicación para la disfunción eréctil (DE) o la libido, desde el período de selección hasta el final de la fase doble ciego de estudio (de la visita 1 a la visita 8), incluidos los tratamientos fitoterápicos y las medicaciones sin receta.
[8] En caso de que el individuo esté recibiendo tratamiento de restitución con testosterona y esté dispuesto a interrumpir dicho tratamiento para participar en el estudio, la concentración de testosterona correspondiente al período de selección no deberá determinarse al menos hasta que hayan transcurrido 14 días desde la interrupción del tratamiento oral o tópico (o al menos 30 días desde que el paciente haya estado recibiendo tratamientos intramusculares [IM] de acción corta [cipionato de testosterona o enantato de testosterona], o al menos 6 meses ?en el caso de los pacientes que estén recibiendo undecanoato de testosterona IM de acción prolongada?). |
|
| E.4 | Principal exclusion criteria |
[1] Sexual partner who is, or becomes, pregnant at any time during the study.
[2] Use of long-acting IM testosterone undecanoate or testosterone pellets in the 6-month period prior to screening.
[3] BMI >37kg/m2 at screening.
[4] Severe lower urinary tract symptoms as well as significant prostate enlargement to the extent that the investigator does not believe that the patient should receive testosterone replacement therapy.
[5] Prolactin lab test result of >30 ng/dL at screening.
[6] HbA1c >11% at screening.
[7] Hematocrit ?50% at screening. For sites located at geographic elevations ?4500 feet (approximately 1370 meters), patients will be excluded with hematocrit >54% at screening, according to investigator discretion. If any patient at any site regardless of geographic elevation develops hematocrit >54% at later study visits investigational product will be discontinued immediately.
[8] Significant history of allergy and/or sensitivity to the drug products or excipients, including any history of sensitivity to testosterone and/or sunscreens.
[9] Current use of any medications, herbal, and/or nutritional supplements that can interfere with testosterone.
[10] Dermatologic condition in underarm area that might interfere with testosterone absorption or be exacerbated by topical testosterone replacement therapy.
[11] Currently receiving treatment with cancer chemotherapy or antiandrogens.
[12] Current use of systemic glucocorticoids. Use of non-testosterone anabolic steroids within 12 months prior to screening.
[13] Competitive athletes involved in a sport in which they may be screened for anabolic steroids.
[14] History of use of estrogenizing agents within 12 months prior to screening.
[15] History of luteinizing hormone-releasing hormone antagonist or agonist treatment in the last 6 months prior to screening.
[16] History of clomiphene or other anti-estrogen treatment in the 3 months prior to screening.
[17] Use of finasteride within 3 months prior to screening, or use of dutasteride within 6 months prior to screening.
[18] Current use of warfarin.
[19] History of frequent opioid use (>1 time/week) within 30 days prior to screening.
[20] Current use of dopamine receptor agonists (cabergoline, pergolide, bromocriptine).
[21] History of drug, alcohol, or substance abuse within 6 months prior to screening, as assessed by the investigator.
[22] Have a history of significant central nervous system injuries or disease within 6 months prior to screening.
[23] Exhibit systolic blood pressure >170 or <90 mm Hg or diastolic blood pressure >100 or <50 mm Hg at screening, or have history of malignant hypertension.
[24] History of unstable angina or angina occurring during sexual intercourse in the last 6 months.
[25] History of any of the following coronary conditions within 90 days of screening:
a. myocardial infarction
b. coronary artery bypass graft surgery
c. percutaneous coronary intervention (angioplasty or stent placement)
[26] Have any supraventricular arrhythmia with an uncontrolled ventricular response (mean heart rate >100 beats per minute [bpm]) at rest, or have any history of spontaneous or induced sustained ventricular tachycardia (heart rate >100 bpm for ?30 seconds), or use an automatic internal cardioverter-defibrillator.
[27] Have a history of sudden cardiac arrest.
[28] Exhibit any evidence of congestive heart failure within 6 months prior to screening.
[29] Have had a new, significant cardiac conduction defect within 90 days prior to screening.
[30] Clinical suspicion (or history) of prostate cancer during digital rectal examination at the time of screening.
[31] Known or suspected breast cancer (or history of breast cancer) or other active cancer (with the exception of nonmelanotic skin cancer).
[32] Exhibit evidence of severe renal impairment at the time of screening.
[33] Exhibit a history of severe liver disease or clinical evidence of hepatic impairment at the time of screening.
[34] Have a history of human immunodeficiency virus (HIV) infection or a sexually transmitted disease.
[35] Severe sleep apnea (untreated or unsuccessfully treated) in the opinion of the study investigator.
[36] Untreated hypothyroidism, hypercortisolism or other significant endocrinopathy (other than hypogonadism) that, in the opinion of the investigator, contributes to symptoms of low energy or fatigue.
Additionally for the open-label extension phase:
[37] Any clinically significant chronic illness or finding and/or laboratory results that would interfere with the trial objectives or safety of the patient. |
[9] Tener una pareja sexual que esté o se quede embarazada durante el estudio.
[10] Haber recibido testosterona IM de acción prolongada o cápsulas de testosterona en el período de 6 meses
[11] Presentar un IMC > 37 kg/m2 en la V 2.
[12] Presencia de síntomas intensos en las vías urinarias inferiores, así como hipertrofia significativa de la próstata.
[13] Prolactina > 30 ng/dl en V 2
[14] HbA1c >11% en V 2.
[15] Hematocrito ? 50% en V2
[16] Antecedentes significativos de alergia y/o sensibilidad a los productos farmacológicos o excipientes, a testosterona y/o filtros solares.
[17] Estar recibiendo cualquier medicación, tratamiento fitoterápico y/o complementos nutricionales que puedan interferir con la testosterona.
[18] Presentar un trastorno dermatológico en la axila.
[19] Estar recibiendo tratamiento quimioterápico antineoplásico o antiandrógenos.
[20] Estar recibiendo glucocorticoides sistémicos. Haber recibido esteroides anabólicos en el transcurso de los 12 meses previos a la visita 1.
[21] Ser un atleta de competición que practique un deporte en el que pueda someterse a pruebas de detección de esteroides anabólicos.
[22] Antecedentes de uso de fármacos estrogenizantes en el transcurso de los 12 meses previos a la V1.
[23] Antecedentes de tratamiento con antagonistas o agonistas de la hormona liberadora de hormona luteinizante en el transcurso de los 6 meses previos a la V1.
[24] Antecedentes de tratamiento con clomifeno u otro antiestrógeno en el transcurso de los 3 meses previos a la visita 1.
[25] Uso de finasterida en los 3 meses previos a la visita 1, o uso de dutasterida en los 6 meses previos a la visita 1.
[26] Estar recibiendo en la actualidad warfarina.
[27] Antecedentes de uso frecuente de opioides, en los 30 días previos a la V1.
[28] Estar recibiendo agonistas del receptor de dopamina.
[29] Antecedentes de abuso de sustancias, toxicomanías o alcoholismo en los 6 meses previos a la V1.
[30] Antecedentes de lesiones o enfermedades significativas que afecten al sistema nervioso central en los 6 meses previos a la V1.
[31] Presentar, en V1, presión arterial sistólica >170 ó < 90 mm Hg, o de presión arterial diastólica > 100 ó < 50 mm Hg, o antecedentes de hipertensión maligna.
[32] Antecedentes de angina inestable o angina que se haya producido durante el coito en el transcurso de los últimos 6 meses.
[33] Antecedentes de cualquiera de las siguientes enfermedades coronarias en el transcurso de los 90 días previos a V1: Infarto de miocardio, Revascularización coronaria, Intervención coronaria percutánea (angioplastia o colocación de una endoprótesis vascular).
[34] Presentar, en reposo, arritmia supraventricular con respuesta ventricular incontrolada, o taquicardia ventricular espontánea o taquicardia ventricular inducida sostenida o utilización de un desfibrilador automático interno.
[35] Antecedentes de paro cardiaco súbito.
[36] Presentar indicios de insuficiencia cardiaca congestiva, en los 6 meses previos a la V1.
[37] Presentar un nuevo defecto significativo de conducción cardiaca, en los 90 días previos a la V1.
[38] Sospecha clínica de cáncer de próstata durante el tacto rectal en la V2.
[39] Presencia de cáncer de mama u otro cáncer activo
[40] Presentar indicios de insuficiencia renal grave en V2.
[41] Presentar antecedentes de enfermedad hepática grave o indicios clínicos de insuficiencia hepática en la V1 y/o en V2.
[42] Antecedentes de infección por el VIH o de enfermedad de transmisión sexual.
[43] Presentar apnea del sueño intensa.
[44] Hipotiroidismo, hipercortisolismo u otra endocrinopatía significativa sin tratar que contribuya a los síntomas de poca energía o fatiga.
[45] Presentar cualquier enfermedad que pueda interferir con la capacidad del paciente para proporcionar el consentimiento informado o seguir las instrucciones del protocolo, suponga un mayor riesgo para el paciente o pueda dificultar la interpretación de los resultados del estudio.
[46] Personal del centro de investigación, directamente relacionado con el estudio, y los familiares cercanos.
[47] Empleados de Lilly o de una organización externa que estén implicados en el estudio y que no puedan participar de acuerdo con sus requerimientos internos.
[48] Haber finalizado o haber interrumpido previamente la participación en este estudio o en cualquier otro estudio en el que se investigue el tratamiento con solución de testosterona.
[49] Estar participando en la actualidad o haber abandonado en el transcurso de los 30 días previos un ensayo clínico, en el que se administre un fármaco en fase de investigación, o se haga un uso no recogido en ficha técnica de un fármaco o dispositivo, o estar participando en la actualidad en cualquier otro tipo de investigación médica que se considere que no es compatible con el estudio, desde un punto de vista científico o médico. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint of the double blind phase is to determine the proportion of men that have a serum total testosterone level within the normal range (300 ? 1050 ng/dL) at the completion of 12 weeks of treatment with testosterone solution.
The primary endpoint of the open-label extension is to assess long term safety by collecting the following measures:
? Adverse events
? Clinical laboratory tests (including hematocrit)
? Prostate safety (prostate specific antigen [PSA] and digital rectal exam)
? International Prostate Symptom Score (IPSS)
at the completion of the additional 24 weeks of treatment with testosterone solution . The measures will be compared to the baseline visit of the double-blind phase and the baseline visit of the open-label extension phase. |
El objetivo principal de este estudio es comparar el efecto de la solución de testosterona con el de placebo, en relación con la proporción de varones con hipogonadismo que presenten una concentración sérica total de testosterona dentro de la normalidad (300 ? 1050 ng/dl), una vez que hayan completado 12 semanas de tratamiento.
El objetivo principal de la fase de extensión desenmascarada (FED) del estudio TSAT es evaluar la seguridad de la solución de testosterona en varones con hipogonadismo durante un período adicional de 24 semanas, basándose en las siguientes medidas:
? Acontecimientos adversos
? Análisis clínicos (incluida la prueba de hematocrito).
? Seguridad prostática (antígeno prostático específico [PSA] y tacto rectal).
? Puntuación Internacional de los Síntomas Prostáticos (IPSS) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Double blind phase:
12 weeks of treatment
Open-label extension phase:
Total of 36 weeks of treatment (12 weeks treatment during double-blind phase + 24 weeks treatment during open-label extension) |
Fase doble ciego: 12 semanas de tratamiento
Fase abierta de extension
Total 36 semanas de tratamiento (12 semanas de trateminto en la fase doble ciento + 24 semanas de tratemitnto durante la fase abierta de extension) |
|
| E.5.2 | Secondary end point(s) |
The secondary endpoints of the double blind phase are:
1. In patients with low sex drive, the change in levels of sexual arousal, interest and drive as assessed by a patient reported outcome tool, the SAID (Sexual Arousal, Interest and Drive) Scale at the completion of 12 weeks of treatment with testosterone solution.
2. In patients with low energy, the change in energy level as assessed by a patient reported outcome tool, the HED (Hypogonadism Energy Diary) at the completion of 12 weeks of treatment with testosterone solution. |
En pacientes con poco deseo sexual, el cambio en los nives de excitación sexual. el interés y el deseo sexual del paciente según la herramienta escala SAID completada a las 12 semanas con el tratamiento de solución de testosterona,
En pacientes con baja energía, en relación con el grado de energía, de acuerdo con la variación observada respecto a la puntuación basal en el Diario de Energía en el Hipogonadismo (HED). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 4 weeks of treatment
2. 12 weeks of treatment |
1. 4 semanas de tratamiento
2. 12 semanas de tratamiento |
|
| 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 | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Open label extension phase |
|
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Brazil |
| Canada |
| Germany |
| Italy |
| Korea, Republic of |
| Puerto Rico |
| Russian Federation |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| LVLS |
| Ultima visita Ultimo paciente |
|
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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