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

NCT00244023 | Completed Phase 3 DMC

• 1 other identifier: TADTEST
• Study Type: interventional
• Target: 173
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Erectile Dysfunction; Hypogonadism

Keywords

Erectile Dysfunction; Testosterone; Testosterone Therapy; PDE V Inhibitor; Tadalafil

Outcome Measures

Primary Outcomes (1)

• 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.

  V3,V4,V5,End Point

Secondary Outcomes (7)

• Rate of "responders" to treatment

  V3,V4,V5,End Point

• Rate of the patients having achieved a score > 26 at the EFD of the IIEF

  V3,V4,V5,End Point

• Mean scores at Questions 3 and 4 of the IIEF

  V3,V4,V5,End Point

• 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

  V3,V4,V5,End Point

• % of "YES" responses at questions 2, 3, 4 and 5 of the SEP

  V3,V4,V5,End Point

Study Arms (2)

1

EXPERIMENTAL

Testosterone gel (intervention)

Drug: Testosterone gel; Drug: testosterone

2

PLACEBO COMPARATOR

one sachet of placebo gel once a day, possibly titrated to 2 sachets if insufficient efficacy

Other: placebo gel

Interventions

Testosterone gel DRUG

one sachet of 50 mg applied once a day, possibly titrated to two sachets if insufficient improvement of erectile function

Also known as: Androgel or Testogel

1

testosterone DRUG

testosterone gel, one sachet of 50 mg applied once a day, possibly titrated to 100 mg if insufficient effect

Also known as: Testogel or Androgel

1

placebo gel OTHER

one sachet of placebo gel once a day possibly titrated to 2 sachets if insufficient efficacy

2

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ED complaint ongoing for over 3 months;
• Age comprise between 45 and 80 years old;
• Had a stable heterosexual relationship for more than 3 months and anticipates having the same partner for all the study
• 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
• 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
• 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
• 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?").
• 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
• Agrees not to use any other ED drug or non-drug (devices) treatment during the full course of the study;
• Provides a signed informed consent.

You may not qualify if:

• Impotence caused by other primary sexual disorder (e.g. premature ejaculation);
• History of penile implant or significant penile deformity;
• Body mass index \>35kg/m2;
• Diabetes mellitus that is uncontrolled (HbA1c level \> 10%). HbA1c will be checked at screening for each diabetic patient or suspected to be;
• Uncontrolled thyroid disorders;
• Known hyperprolactinemia (serum prolactin \> 30ng/ml in local laboratory);
• Organic hypothalamic-pituitary pathology;
• History of alcohol, drug or substance abuse within 6 months before Visit 1;
• Renal insufficiency defined as receiving renal dialysis, having a creatinine clearance \< 30 ml/mn, or serum creatinine \> 30 mg/ml;
• Severe hepatic impairment, Child Pugh class C, elevation of AST and/or ALT \> 3 x the ULN;
• Systolic Blood Pressure \> 170 or \< 90 mm Hg or diastolic blood pressure \> 110 or \< 50 mm Hg at screening;
• Cardiac disease contra-indicating any sexual activity;
• Unstable angina within 6 months before Visit 1;
• Angina during sexual intercourse within 6 months before Visit 1;
• Myocardial Infarction within 90 days before Visit 1;

Sponsors & Collaborators

• SELARL du Dr Jacques BUVAT: lead
• Bayer: collaborator

Study Sites (1)

CETPARP/SelarlJBuvat

Lille, 59000, France

Location

Related Publications (1)

• Lee H, Hwang EC, Oh CK, Lee S, Yu HS, Lim JS, Kim HW, Walsh T, Kim MH, Jung JH, Dahm P. Testosterone replacement in men with sexual dysfunction. Cochrane Database Syst Rev. 2024 Jan 15;1(1):CD013071. doi: 10.1002/14651858.CD013071.pub2.

  PMID: 38224135 DERIVED

MeSH Terms

Conditions

Erectile Dysfunction; Hypogonadism

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Sexual Dysfunctions, Psychological; Mental Disorders; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Jacques BUVAT, MD

  SELARL du Dr Jacques BUVAT

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 23, 2005
• First Posted: October 25, 2005
• Study Start: October 1, 2005
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: August 25, 2008

Record last verified: 2008-08

Locations

FR (1)