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Retrospective analysis of the efficacy and safety of once-daily tadalafil in patient subgroups: men with mild vs moderate ED and aged <50 vs 50 years

Abstract

The aim of this post-hoc pooled-data analysis was to evaluate the effects of once-daily tadalafil in men with mild or moderate ED and aged <50 or 50 years. Data from three randomized controlled trials were analyzed. Analysis of covariance models included a term for ED severity and age group. The three coprimary outcome measures in the base studies were changes from baseline to end point in the mean International Index of Erectile Function Erectile Function (IIEF-EF) domain score and the mean per-patient percentage successful vaginal penetration and intercourse attempts. Irrespective of baseline severity, once-daily tadalafil 5 mg for 12 weeks compared with placebo significantly increased the mean: (1) IIEF-EF by 6.8; (2) percent successful penetration attempts from 70.1 to 91.3%; and (3) percent successful intercourse attempts from 33.4 to 76.8% (each P<0.001). Treatment-by-age-group interaction P-values for all three coprimary efficacy end points exceeded 0.10, indicating that tadalafil treatment effects did not differ by age <50 vs 50 years. Tadalafil was generally well tolerated.

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Acknowledgements

Assistance in manuscript preparation was provided by Stephen W Gutkin, Rete Biomedical Communications Corp. (Wyckoff, NJ, USA), with support from Eli Lilly and Company (Indianapolis, IN, USA), which had a role in the designs of both the base studies and the present analysis; data acquisition and interpretation; drafting of the manuscript; and the decision to report the findings. Statistical assistance was provided by Sunny Li, MS, inVentiv Clinical (Somerset, NJ, USA), with support from Eli Lilly, as well as from Cheolho Park, PhD, of Eli Lilly. We also thank Anne Esler, PhD, Senior Biostatistician, PharmaNet/i3 inVentiv Clinical (Indianapolis, IN, USA), for reviewing and commenting on the manuscript.

Author contributions

Conception and design: all authors. Acquisition of data: Drs Seftel, Shinghal, Kim and Samuels, along with the clinical investigators in the base studies. Analysis and interpretation of data: Dr Ni conducted statistical analyses (with assistance from Ms Li and Dr Park), and all authors interpreted data. Drafting the article: Drs Seftel, Shinghal and Kim with assistance from Mr Gutkin. Revising it for intellectual content: all authors. Final approval of the completed article: all authors. Dr Seftel had access to all data analyzed and takes responsibility for the analysis and this report.

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Correspondence to A D Seftel.

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Competing interests

Dr Seftel is a paid consultant to Abbott, Auxilium, Eli Lilly, Endo and Pfizer, and has received research grants from Eli Lilly and Auxilium. Dr Shinghal is an advisor to Eli Lilly and PercSys, a clinical investigator for GlaxoSmithKline, and a speaker for Astellas. Dr Kim is an advisor, recipient of honoraria, and a paid consultant/investigator for Eli Lilly. He is also a speaker for Astellas, Auxilium and Watson. Dr Samuels holds stocks (or options) in Eli Lilly (minor). Drs Ni and Burns are employees of, and stock (or option) holders in, Eli Lilly (minor).

Appendix

Appendix

Eligibility criteria for subjects enrolled in the base studies,23, 27, 28

Inclusion criteria

  • Age 18 years.

  • Minimum 3-month history of ED.

  • ED of any severity or etiology.

Exclusion criteria

  • ED secondary to other primary sexual disorders (e.g., premature ejaculation) or to untreated endocrine disorder (e.g., hypogonadism, hypothyroidism).

  • History of (non-nerve-sparing) radical prostatectomy or other pelvic surgery with subsequent failure to achieve erection

  • Clinically significant penile deformity or penile implant (prosthesis).

  • Clinically significant renal or hepatobiliary disease.

  • Significant spinal-cord or other central-nervous-system injury (e.g., stroke) within 6 months before screening

  • History of human immunodeficiency virus infection.

  • Current treatment with nitrates, cancer chemotherapy,23, 28 or anti-androgens23, 28 (finasteride and dutasteride were permitted in Study H6D-MC-LVGH23).

  • Recent histories of unstable or poorly controlled cardiovascular disorders, including:

    • Unstable angina within the past 6 months.

    • Congestive heart failure (New York Heart Association Class II or higher) within prior 6 months.

    • Myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention within the prior 90 days.

  • Supraventricular arrhythmia with uncontrolled ventricular response at rest, or history of spontaneous or induced sustained ventricular tachycardia, despite medical or device therapy; or the presence of an automatic internal cardioverter-defibrillator.

  • Extremes of blood pressure at screening: 90 mm Hg>systolic blood pressure>170 mm Hg or 50 mm Hg>diastolic blood pressure>100 mm Hg or malignant hypertension.

  • Hemoglobin A1c>13%.

  • History of alcohol, drug, or substance abuse within the prior 6 months.

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Seftel, A., Shinghal, R., Kim, E. et al. Retrospective analysis of the efficacy and safety of once-daily tadalafil in patient subgroups: men with mild vs moderate ED and aged <50 vs 50 years. Int J Impot Res 25, 91–98 (2013). https://doi.org/10.1038/ijir.2012.40

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