Clinical trial: Double-Blind, Placebo Controlled Randomized Study of Co-Administering Testosterone With PDE5 Inhibitors in Patients Non-Responders to PDE5 Inhibitors Alone (NCT00244023)

Eligibility criteria:
Inclusion Criteria:

          1. ED complaint ongoing for over 3 months;

          2. Age comprise between 45 and 80 years old;

          3. Had a stable heterosexual relationship for more than 3 months and anticipates having
             the same partner for all the study

          4. Has not responded adequately to the highest available dosage of Tadalafil or other
             PDE5 inhibitors (20 mg for Tadalafil and Vardenafil, 100 mg for Sildenafil) taken at
             least at 4 separate occasions, defined as: a score of 2,3 or 4 at Question 3 of the
             IIEF AND a score of 2 or 3 at Question 4 of the IIEF; measured prior to Visit 1

          5. Low or low-to-normal serum testosterone level (either on total or bioavailable
             testosterone levels) with respect to the range of men under aged than 50 y.o. (TT < 4
             ng/ml and/or BT < 1 ng/ml) according to a first assay done prior to Visit 1 and a
             confirmation by a second assay at central laboratory Biolille on blood sampled at
             Visit 1

          6. Agrees to make at least 4 attempts at sexual intercourse on 4 separate days during the
             4 weeks run-in period with daily Tadalafil 10 mg

          7. At least 50% of attempts during this period must be unsuccessful according an answer
             "No" at one of the questions 1 ("were you able to achieve at least some erection (some
             enlargement of the penis)?"), 2 ("were you able to insert your penis in your partner's
             vagina?") or 3 ("did your erection last long enough for you to have successful
             intercourse?").

          8. At the end of the run in phase with Tadalafil 10 mg daily, the patient should provide:
             a score of 2, 3 or 4 at Question n°3 of the IIEF AND a score of 2, 3 at Question n°4
             of the IIEF

          9. Agrees not to use any other ED drug or non-drug (devices) treatment during the full
             course of the study;

         10. Provides a signed informed consent.

        Exclusion Criteria:

          1. Impotence caused by other primary sexual disorder (e.g. premature ejaculation);

          2. History of penile implant or significant penile deformity;

          3. Body mass index >35kg/m2;

          4. Diabetes mellitus that is uncontrolled (HbA1c level > 10%). HbA1c will be checked at
             screening for each diabetic patient or suspected to be;

          5. Uncontrolled thyroid disorders;

          6. Known hyperprolactinemia (serum prolactin > 30ng/ml in local laboratory);

          7. Organic hypothalamic-pituitary pathology;

          8. History of alcohol, drug or substance abuse within 6 months before Visit 1;

          9. Renal insufficiency defined as receiving renal dialysis, having a creatinine clearance
             < 30 ml/mn, or serum creatinine > 30 mg/ml;

         10. Severe hepatic impairment, Child Pugh class C, elevation of AST and/or ALT > 3 x the
             ULN;

         11. Systolic Blood Pressure > 170 or < 90 mm Hg or diastolic blood pressure > 110 or < 50
             mm Hg at screening;

         12. Cardiac disease contra-indicating any sexual activity;

         13. Unstable angina within 6 months before Visit 1;

         14. Angina during sexual intercourse within 6 months before Visit 1;

         15. Myocardial Infarction within 90 days before Visit 1;

         16. Coronary artery by-pass graft surgery or percutaneous coronary intervention
             (angioplasty or stent insert) within 90 days before Visit 1;

         17. Severe cardiac rhythm disturbances e.g. supraventricular arrhythmia with a ventricular
             response >100 bpm. at rest despite medical or device therapy, history of refractory
             spontaneous or induced sustained ventricular tachycardia (heart rate > 100 bpm. for >
             30 sec) or fibrillation, automatic internal cardioverter-defibrillator, history of
             sudden cardiac arrest) within 6 months before Visit 1;

         18. Known new and significant conduction defect that was not evaluated with regard to
             significance within 90 days prior to Visit 1;

         19. Congestive heart failure (NYHA Class II or above) within 6 months before Visit 1;

         20. History of stroke within the 6 last months;

         21. Epilepsy not adequately controlled by treatment;

         22. Polycythemia with hematocrit >52% at study entry (i.e. screening visit/visit 1);

         23. Suspicion of current, or past history of prostate or breast cancer;

         24. Severe symptomatic Benign Prostate Hyperplasia;

         25. PSA value exceeding the age specific reference ranges published by Richardson and
             Oesterling, Urol Clin North Am, 1997, 24: 339-351

         26. Diagnosed sleep apnea;

         27. Extensive skin abnormalities that could affect absorption of the gel;

         28. Any clinically significant chronic disease that might, in the opinion of the
             investigator, compromise patient's safety, interfere with the evaluations, or preclude
             completion of the trial (e.g. hemochromatosis, chronic lung disease, chronic
             malabsorption disease);

         29. History of HIV infection;

         30. Severe psychiatric disease;

         31. Illiteracy, lack of fluency in the language used for the writing of the protocol and
             questionnaires, unwillingness, medical, psychiatric or other conditions that
             compromise the patient's ability to understand the patient information, to give
             informed consent, to understand or complete diary or questionnaires or otherwise
             comply with the trial protocol, or to complete the study;

         32. Known hypersensitivity to Cialis(Tadalafil);

         33. Hypersensitivity to the active substances or any of the excipients of Androgel®/
             Testogel®;

         34. Use of androgen therapy or anabolic steroids within 6 months of entry into the study
             (i.e. screening visit/visit 1);

         35. Concurrent use of the following medications:

             androgens including dehydroepiandrosterone (DHEA) and anabolic steroids,
             antiandrogens, estrogens, corticotrophin (ACTH), oxyphenylbutazone, clomipramine,
             Serotonin Reuptake Inhibitors, long or short-acting nitrates, NO donors, potent
             cytochrome P3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir, saquinavir,
             macrolides like erythromycin), cancer chemotherapy;

         36. Patients unwilling to cease use of vacuum devices, intracavernosal injection, Viagra,
             or other therapy for ED;

         37. Patients seeking conception or on treatment for infertility;

         38. Concurrent participation in another clinical trial within 1 month of entry into this
             study (i.e. screening visit/visit 1) or throughout the duration of the study;

         39. Previous randomization into this study.

         40. History of temporary or permanent partial or complete blindness
Male
No healthy subjects accepted to join the trial.
Subject must be at least 45 Years old.
Subject must be at most 80 Years

Patient description (medical language): A 19-year-old male came to clinic with some sexual concern.  He recently engaged in a relationship and is worried about the satisfaction of his girlfriend. He has a "baby face" according to his girlfriend's statement and he is not as muscular as his classmates.  On physical examination, there is some pubic hair and poorly developed secondary sexual characteristics. He is unable to detect coffee smell during the examination, but the visual acuity is normal. Ultrasound reveals the testes volume of 1-2 ml. The hormonal evaluation showed serum testosterone level of 65 ng/dL with low levels of GnRH.

Patient description (patient's own words): I'm 19 years old guy and I just went to see a doctor at the clinic after I just got with my girlfriend. I'm kinda worried because she thinks that I have a baby face and to be honest, I'm way less muscular than my classmates. I don't have much hair down there, and yes, I don't have that macho look. The doctor made me smell some coffee and I couldn't smell anything special. I also had some eyesight checkups and the doctor told me everything was normal. I got my test results back and it says: testes volume is 1-2 ml and serum testosterone level of 65 ng/dL with low GnRH levels.

Does the patient match the trial criteria? Contradiction