E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypogonadotropic hypogonadism in men with pituitary damage other than irradiation |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021012 |
E.1.2 | Term | Hypogonadotrophic hypogonadism |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether hypogonadotropic hypogonadism in patients with pituitary disease is reversible with Letrozole. To determine the minimal effective dose to normalize serum testosterone. To determine whether Letrozole normalizes diurnal rhythm of LH and testosterone secretion. To determine whether Letrozole stimulates FSH production and thereby increases semen quantity. To determine the effects of long term Letrozole treatment on bone mass and metabolism. |
|
E.2.2 | Secondary objectives of the trial |
To study the effects on bone metabolism. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male -Age: 18-50 years -Hypogonadotropic hypogonadism: serum total testosterone 2-10 nmol/L and calculated serum free testosterone < 225 pmol/L and serum LH < 9 U/L -Pituitary damage on MRI: (hormonally inactive) pituitary adenoma or partial empty sella -Residual LH and FSH secretion, as indicated bij the presence of detectable serum LH and FSH levels in the basal state, i.e. levels > 1 U/L ( after 4 weeks withdrawal of testosterone replacement therapy) -Testicular length on palpation > 1 cm -Adequate and stable replacement therapy for pituitary hormone deficiencies other than LH and FSH |
|
E.4 | Principal exclusion criteria |
-Pituitary irradiation -Untreated pituitary adenoma associated with compression of the optic chiasm -Benign or malignant diseases of the prostate -Osteoporosis: T-score Lumbal Spine of hip < -2.5 sd -Renal failure:serum creatinin > 150 micromol/L -Liver disease: liver enzymes > 2 times the upper normal limit -Unstable chronic illness -Any mental disturbance -Non-endocrine medication known to affect Letrozole availability or bone metabolism |
|
E.5 End points |
E.5.1 | Primary end point(s) |
-The minimal effective dose to normalize serum testosterone. -To determine whether Letrozole normalizes diurnal rhythm of LH and testosterone secretion. -To determine whether Letrozole stimulates FSH production and thereby increases semen quantity -To determine the side effects of long term Letrozole treatment |
|
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
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
|
Letrozole will be prematurely discontinued if: -Serum PSA rises to a level above 4.0 U/L in two measurements performed within 4 weeks and without evidence of infection. -New and progressive symptoms of lower urinary obstruction, with or without an increase of PSA. -A decrease in bone mineral density of more than 5% in 2 years -Persistence of side effects possibly realted to Letrozole -Wish of the patient/ side effects |
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |