Safety and Clinical Effectiveness of 2 Lower Dose Combined PDE5i's vs. Single Maximal Dose PDE5i

• ClinicalTrials.gov Identifier: NCT00498680
• Recruitment Status: Unknown
• First Posted: July 10, 2007
• Last Update Posted: October 22, 2010
• Sponsor: Rambam Health Care Campus
• Information provided by: Rambam Health Care Campus

Tracking Information

• First Submitted Date: July 8, 2007
• First Posted Date: July 10, 2007
• Last Update Posted Date: October 22, 2010
• Study Start Date: March 2007
• Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 11, 2010): increase of 5 points or more in the IIEF erectile function domain [ Time Frame: 1 month ]

Original Primary Outcome Measures (submitted: July 9, 2007)

• Safety- Decrease of 20 mmhg and above in systolic or dioastolic blood pressure up to 5 hours (measuring every hour) after half dose combination intake.
• Efficacy- Significant questionnaire scores compared between all 3 groups.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Clinical Effectiveness of 2 Lower Dose Combined PDE5i's vs. Single Maximal Dose PDE5i
• Official Title: A Prospective, Randomized, 3-arm Parallel Trial to Evaluate the Safety and Clinical Effectiveness of 2 Lower Dose Combined PDE5i's vs. Single Maximal Dose PDE5i Treatment
• Brief Summary: A prospective, randomized, 3-arm parallel trial on 45 males with ED that were never exposed to PDE5i therapy (naïve patients) will be enrolled.In each group, every patient will receive three treatment regimes (Viagra®50mg & Levitra®10mg, Viagra®100mg, Levitra®20mg), in different sequences of administration in such a manner that eventually each patient will receive all regimes in a double- blinded fasion.Safety will be evaluated at pre- screening by measuring hourly vital signs (blood pressure, heart rate)for 4 consecutive hours after taking half-dose combination. Any decrease in blood pressure of 20 mmhg below baseline will exclude the subject from the study. Effcacy will be evaluated by questionnaires (IIEF, Quality of erection questionnaire, grade of erection scale, Sear, QVS and Sexual Encounter Profiles for each sexual event). Non-parametric statistical analysis of the collected data Comparing the 3 groups will be performed.

Detailed Description

A prospective, randomized, 3-arm parallel trial on 45 males with ED that were never exposed to PDE5i therapy (naïve patients) will be enrolled. Recruitment will be performed via advertisement or by offering newly diagnosed naïve ED patients visiting the clinic to participate in the study.

In each group, every patient will receive three treatment regimes (Viagra®50mg & Levitra®10mg, Viagra®100mg, Levitra®20mg), in different sequences of administration, as follows:

Group 1) 15 naïve patients will start with Viagra®100mg, continue with Levitra®20mg and end the study with combined Viagra®50mg & Levitra®10mg.

Group 2) 15 naïve patients will start with combined Viagra®50mg & Levitra®10mg, continue with Levitra®20mg and end the study with Viagra®100mg.

Group 3) 15 naïve patients will start with Levitra®20mg, continue with Viagra®100mg and end the study with combined Viagra®50mg & Levitra®10mg.

Inclusion criteria: - Relationship with the same partner for at least 3 month

• Age ranging between 35-65 years old
• Sexually active, (minimal frequency of one sexual encounter per 2 weeks)
• IIEF ED domain score 22 and below. Exclusion criteria: - Subjects with premature ejaculation as their main sexual complaint.
• Subjects with severe cardiovascular disease in the past 6 months, including cardiac failure, myocardial infarction, unstable angina, stroke or transient ischemic attack, symptomatic or clinically significant cardiac arrhythmias including atrial fibrillation,
• Subjects with Contraindications to PDE5i therapy. Namely patients receiving treatment with nitrate based medication or patients that for various reasons cannot take PDE5 inhibitors (severe hepatic diseases- cirrhosis or ALT (Alanine aminotransferase)>2x upper limit of normal), renal impairment (creatinine clearance > 30ml/min) or known hereditary degenerative retinal disorders such as retinitis pigmentosa. ,
• Concomitant treatment with potent CYP3A4 and CYP2C9 inhibitors (e.g protease inhibitors ritonavir and saquinavir, ketoconazole, itrakonazole, miconazole, nefazodone, claritromycin, troleandomycin, erythromycin and cimetidine)
• Subjects mentally unfit for the study.

SAFETY & ELIGIBILITY VISIT. After a thorough explanation of the nature of the study and its protocol and after understanding and signing the informed consent form. In this visit, each subject will start the study by measuring basic blood pressure levels and pulse rate. Under our supervision the subject will take the combined half dose as suggested. Blood pressure monitoring and pulse rate every half- hour at the clinic will be performed for 4 hours (according to the pharmacokinetic properties of the medications) . Any recordings of 20 mmhg below baseline will exclude the subject from the study. If no significant effect on blood pressure will be noted, the subject will be eligible for inclusion in the study, and will be invited for the FIRST visit 7 days later. ( a washout period of one week is sufficient to eliminate any effect of one-time dosing of the combined half dose treatment). Each included patient in the coming 6 visits will respond to the following pre-set sexual function and satisfaction questionnaires (Hebrew validated):

1. The full IIEF (International Index Erectile Function) standard Questionnaire
2. The SEAR (Self-Esteem And Relationship) questionnaire
3. QVS (Quality of Sexual Life) questionnaire
4. Quality of erection questionnaire
5. Grade of erection scale

At each visit, documentation of side-effects will be done and a physical examination (blood pressure and pulse rate) will be done. A 24 hour mobile phone dedicated to patient inquiries will be provided to each patient during the whole study.

Visit 1: The subject will be offered, at random, for 4 attempts at home, either a combination dose regime (Viagra®50mg & Levitra®10mg, 4 tablets each) or 4 tablets of Viagra®100mg single dose or 4 tablets of Levitra® 20 mg. The subject will also receive 6 SEP (Sexual Encounter Profile) diaries to fill out at home after each sexual attempt. After 4 attempts the subject will return for visit 2, will respond to the same questionnaires and an additional EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction) questionnaire. A new visit will be rescheduled for 2 weeks later to allow a washout period. At visit 3 they will receive the 2nd regime and 4 new SEP diaries, and after 4 attempts will return to visit 4, fill out the same 4 questionnaires. Again, a new visit will be rescheduled for 2 weeks later to allow a washout period. On visit 5 they will return to receive the third treatment regime. Again, they will receive 4 SEP diaries to fill out after each sexual attempt at home. At their final visit (visit 6), in addition to the other 4 questionnaires, the patients will be required to respond to a preference questionnaire regarding the preferred regime.

The approximate timeline for performing the study for every patient is 1/2 a year from recruitment. The estimated timeline for completion of the study is 16 months.

*Only on inclusion

** Washout period 2 weeks

Non-parametric statistical analysis of the collected data from the questionnaires will be performed.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Impotence

Intervention

• Drug: Sildenafil, Vardenafil
  Sildenafil 100mg, vardenafil 20mg, combination of both half dosage.
  Other Name: Viagra, Levitra
• Drug: Sildenafil
  100mg
• Drug: Vardenafil
  20mg
• Drug: Sildenafil & Vardenafil
  50mg & 10 mg

Study Arms

• Active Comparator: Viagra 100mg
  Intervention: Drug: Sildenafil
• Active Comparator: Levitra 20mg
  Intervention: Drug: Vardenafil
• Active Comparator: Viagra 50mg+ Levitra 10mg
  Interventions:

  • Drug: Sildenafil, Vardenafil
  • Drug: Sildenafil & Vardenafil

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 11, 2010): 46
• Original Estimated Enrollment (submitted: July 9, 2007): 45
• Estimated Study Completion Date: June 2011
• Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Relationship with the same partner for at least 3 month
• Age ranging between 35-65 years old
• Sexually active, (minimal frequency of one sexual encounter per 2 weeks)
• IIEF ED domain score 22 and below.

Exclusion Criteria:

• Subjects with premature ejaculation as their main sexual complaint.
• Subjects with severe cardiovascular disease in the past 6 months, including cardiac failure, myocardial infarction, unstable angina, stroke or transient ischemic attack, symptomatic or clinically significant cardiac arrhythmias including atrial fibrillation,
• Subjects with Contraindications to PDE5i therapy. Namely patients receiving treatment with nitrate based medication or patients that for various reasons cannot take PDE5 inhibitors (severe hepatic diseases- cirrhosis or ALT (Alanine aminotransferase)>2x upper limit of normal), renal impairment (creatinine clearance > 30ml/min) or known hereditary degenerative retinal disorders such as retinitis pigmentosa. ,
• Concomitant treatment with potent CYP3A4 and CYP2C9 inhibitors (e.g protease inhibitors ritonavir and saquinavir, ketoconazole, itrakonazole, miconazole, nefazodone, claritromycin, troleandomycin, erythromycin and cimetidine)
• Subjects mentally unfit for the study.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 35 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT00498680
• Other Study ID Numbers: 2431-ctil
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Prof. Vardi Yoram, RAMBAM HEALTH CARE CAMPUS
• Original Responsible Party: Not Provided
• Current Study Sponsor: Rambam Health Care Campus
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ilan Gruenwald, MD; Israel Urology Association

• PRS Account: Rambam Health Care Campus
• Verification Date: January 2007