Clinical Trial Page

Summary
EudraCT Number:2006-002304-33
Sponsor's Protocol Code Number:no sponsor
National Competent Authority:Netherlands - Competent Authority
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2006-07-21
Trial results
A. Protocol Information
A.1Member State ConcernedNetherlands - Competent Authority
A.2EudraCT number2006-002304-33
A.3Full title of the trial
Letrozole Treatment to Normalize Serum Testosterone in Men with Hypogonadotropic Hypogonadism due to Pituitary Damage.
A.4.1Sponsor's protocol code numberno sponsor
A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorRijnstate Hospital
B.1.3.4CountryNetherlands
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing support
B.4.2Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisation
B.5.2Functional name of contact point
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Femara
D.2.1.1.2Name of the Marketing Authorisation holderNovartis
D.2.1.2Country which granted the Marketing AuthorisationNetherlands
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameFemara
D.3.2Product code RVG 20755
D.3.4Pharmaceutical form Tablet
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNLETROZOLE
D.3.9.1CAS number 112809515
D.3.9.2Current sponsor codeRVG 20755
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number2.5 to mg
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical 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.1.2Version 8.1
E.1.2Level LLT
E.1.2Classification code 10021012
E.1.2Term Hypogonadotrophic hypogonadism
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main 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.2.2Secondary objectives of the trial
To study the effects on bone metabolism.
E.2.3Trial contains a sub-study No
E.3Principal 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.4Principal 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.5.1Primary 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.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response Yes
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans Information not present in EudraCT
E.7.1.2Bioequivalence study Information not present in EudraCT
E.7.1.3Other Information not present in EudraCT
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) Information not present in EudraCT
E.8.2.2Placebo Information not present in EudraCT
E.8.2.3Other 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.8.4.1Number of sites anticipated in Member State concerned2
E.8.5The trial involves multiple Member States No
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
E.8.7Trial 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.8.9.1In the Member State concerned years2
E.8.9.1In the Member State concerned months
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years2
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero Information not present in EudraCT
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
F.1.1.3Newborns (0-27 days) Information not present in EudraCT
F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
F.1.1.5Children (2-11years) Information not present in EudraCT
F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
F.1.2Adults (18-64 years) Yes
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female No
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations No
F.3.3.1Women of childbearing potential not using contraception Information not present in EudraCT
F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
F.3.3.3Pregnant women Information not present in EudraCT
F.3.3.4Nursing women Information not present in EudraCT
F.3.3.5Emergency situation Information not present in EudraCT
F.3.3.6Subjects incapable of giving consent personally Information not present in EudraCT
F.3.3.7Others Information not present in EudraCT
F.4 Planned number of subjects to be included
F.4.1In the member state30
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
After the study the patients will be given the oppurtunity to continue Letrozole treatment or to change to conventional testosterone replacement therapy or to stop treatment without starting conventional testosterone replacement.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2006-07-27
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2006-09-12
P. End of Trial
P.End of Trial StatusOngoing
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