Co-Administering Testosterone With PDE5 Inhibitors in ED Patients Non Responders to PDE5 Inhibitors Alone

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by:
SELARL du Dr Jacques BUVAT
ClinicalTrials.gov Identifier:
NCT00244023
First received: October 23, 2005
Last updated: August 22, 2008
Last verified: August 2008
  Purpose

30 to 50% of the patients presenting with Erectile Dysfunction (ED) do not respond to PDE V Inhibitor therapy, which is presently considered as the first choice treatment for most ED patients. Recent reports stated a high prevalence of low serum testosterone levels in such non responders, and an improvement of their response by combining testosterone therapy with the PDE V Inhibitor. This suggests there may be a minimum threshold level of blood testosterone for a full effectiveness of PDE V Inhibitor therapy. Two double blind, placebo controlled studies have added support to this hypothesis but one involved only 20 patients while in the other the benefit of combining testosterone was transient. This is a multi-centric study, double blind placebo controlled and randomized as concerns testosterone administration, that aims to objectively assess the efficacy of co-administering testosterone with the PDE 5 inhibitor Tadalafil to improve the erectile function of a large group of ED patients non-responders to PDE V inhibitors alone. Patients will be screened to ensure inclusion and exclusion criteria completion, including a serum testosterone level < 4 ng/ml for total testosterone or < 1 ng/ ml for bioavailable testosterone. They will then enter a four week run-in period in the meanwhile they will receive Tadalafil 10 mg only, once daily, in order to confirm their non responsiveness to PDE V inhibitors and their eligibility to enter the treatment phase based on IIEF scoring, SEP diaries and a Global Assessment Question (GAQ). The patients still non responders after 4 weeks of Tadalafil 10 mg daily will enter a 12 weeks treatment phase including visits at weeks 4, 8, 12 and 16. Treatment procedure will include: 1. continuation of Tadalafil at 10 mg dose daily followed by routine assessment using SEP diaries, IIEF scoring, GAQ and Aging Male Symptoms scale administered at each study visit. Safety assessments will be performed in addition during the last visit (physical examination including DRE, PSA and BCC). 2. Randomization in 2 parallel arms (Placebo gel + Tadalafil 10 mg daily, and Testosterone gel 50 mg + Tadalafil 10 mg daily). If indicated according to suboptimal clinical response of the patient, the dose of study medication will be increased at the 8 or 12 weeks visit to 100mg of testosterone or to 2 sachets of placebo gel. Up to 430 patients will be screened in order that 172 are enrolled in the double blind treatment phase.


Condition Intervention Phase
Erectile Dysfunction
Hypogonadism
Drug: Testosterone gel
Drug: testosterone
Other: placebo gel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo Controlled Randomized Study of Co-Administering Testosterone With PDE5 Inhibitors in Patients Non-Responders to PDE5 Inhibitors Alone

Resource links provided by NLM:


Further study details as provided by SELARL du Dr Jacques BUVAT:

Primary Outcome Measures:
  • mean change from baseline in the Erectile Function Domain Score of the IIEF (questions 1-5 + 15) on Tadalafil + Testosterone compared to the one on Tadalafil + placebo. [ Time Frame: V3,V4,V5,End Point ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of "responders" to treatment [ Time Frame: V3,V4,V5,End Point ] [ Designated as safety issue: No ]
  • Rate of the patients having achieved a score > 26 at the EFD of the IIEF [ Time Frame: V3,V4,V5,End Point ] [ Designated as safety issue: No ]
  • Mean scores at Questions 3 and 4 of the IIEF [ Time Frame: V3,V4,V5,End Point ] [ Designated as safety issue: No ]
  • Mean scores at the 4 other domains of the IIEF (Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction Domains), and at the whole IIEF [ Time Frame: V3,V4,V5,End Point ] [ Designated as safety issue: No ]
  • % of "YES" responses at questions 2, 3, 4 and 5 of the SEP [ Time Frame: V3,V4,V5,End Point ] [ Designated as safety issue: No ]
  • Percentage of "YES" responses to the GAQ [ Time Frame: V3,V4,V5,End Point ] [ Designated as safety issue: No ]
  • Scores at the different domains of the AMS questionnaire [ Time Frame: V3,V4,V5,End Point ] [ Designated as safety issue: No ]

Enrollment: 173
Study Start Date: October 2005
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Testosterone gel (intervention)
Drug: Testosterone gel
one sachet of 50 mg applied once a day, possibly titrated to two sachets if insufficient improvement of erectile function
Other Name: Androgel or Testogel
Drug: testosterone
testosterone gel, one sachet of 50 mg applied once a day, possibly titrated to 100 mg if insufficient effect
Other Name: Testogel or Androgel
Placebo Comparator: 2
one sachet of placebo gel once a day, possibly titrated to 2 sachets if insufficient efficacy
Other: placebo gel
one sachet of placebo gel once a day possibly titrated to 2 sachets if insufficient efficacy
Other Name: placebo gel

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   45 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00244023

Locations
France
CETPARP/SelarlJBuvat
Lille, France, 59000
Sponsors and Collaborators
SELARL du Dr Jacques BUVAT
Bayer
Investigators
Study Chair: Jacques BUVAT, MD SELARL du Dr Jacques BUVAT
Principal Investigator: Eugene PLAS, MD Lainz Hospital Vienna - Austria
Principal Investigator: Claude SCHULMAN, MD Erasme Hospital Brussels
Principal Investigator: Francois GIULIANO, MD Hopital Raymond Poincaré - Garches - France
Principal Investigator: Béatrice CUZIN, MD CHU Edouard Herriot - Lyon - France
Principal Investigator: Marie Hélène COLSON, MD Centre du Palais - Marseille - France
Principal Investigator: Hartmut PORST, MD Urological Office - Hamburg - Germany
Principal Investigator: Christian STIEF, MD Ludwig Maximilians Universität - Munchen - Germany
Principal Investigator: Aksam YASSIN, MD Urological Office - Hamburg - Germany
Principal Investigator: Theodor KLOTZ, MD Klinikum fur Urologie - Weiden - Germany
Principal Investigator: Francesco MONTORSI, MD Hospital San Raffaele - Milano - Italy
Principal Investigator: Mario MAGGI, MD Andrology Unit - Florence - Italy
Principal Investigator: Anti KAIPIA, MD Gynecologi - Ja Urologikeskus - Tampere - Finland
Principal Investigator: Eric MEULEMAN, MD Free University Medical Center - Amsterdam - The Netherlands
Principal Investigator: Antonio MARTIN MORALES, MD Hospital Carlos Haya - Malaga - SPAIN
Principal Investigator: Ignacio MONCADA, MD Hospital Gregorio Maranon - Madrid - SPAIN
Principal Investigator: John DEAN, MD Salisbury Clinic - Plymouth - UK
Principal Investigator: Ian EARDLEY, MD Leeds Hospital - Leeds - UK
Principal Investigator: Jacques BUVAT, MD CETPARP - Lille - France
  More Information

No publications provided

Responsible Party: Jacques Buvat, SELARL du Dr Jacques Buvat
ClinicalTrials.gov Identifier: NCT00244023     History of Changes
Other Study ID Numbers: TADTEST
Study First Received: October 23, 2005
Last Updated: August 22, 2008
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by SELARL du Dr Jacques BUVAT:
Erectile Dysfunction
Testosterone
Testosterone Therapy
PDE V Inhibitor
Tadalafil

Additional relevant MeSH terms:
Hypogonadism
Erectile Dysfunction
Gonadal Disorders
Endocrine System Diseases
Sexual Dysfunction, Physiological
Genital Diseases, Male
Sexual Dysfunctions, Psychological
Sexual and Gender Disorders
Mental Disorders
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Phosphodiesterase 5 Inhibitors
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014