A 2-COHORT, MULTI-CENTRE, RANDOMIZED, DOUBLE BLIND (3RD PARTY OPEN), PLACEBO CONTROLLED 4-WAY CROSSOVER STUDY TO ASSESS THE EFFICACY OF SINGLE ORAL DOSES OF PF-00446687 ON ERECTILE FUNCTION IN MEN SUFFERING FROM ERECTILE DYSFUNCTION, USING 100 MG SILDENAFIL AS A POSITIVE CONTROL. - n/a

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-001036-31-GB
• Date of registration: 26/04/2007
• Prospective Registration: Yes
• Primary sponsor: Pfizer Limited, Ramsgate Road, Sandwich, Kent. UK. CT13 9NJ
• Public title: A 2-COHORT, MULTI-CENTRE, RANDOMIZED, DOUBLE BLIND (3RD PARTY OPEN), PLACEBO CONTROLLED 4-WAY CROSSOVER STUDY TO ASSESS THE EFFICACY OF SINGLE ORAL DOSES OF PF-00446687 ON ERECTILE FUNCTION IN MEN SUFFERING FROM ERECTILE DYSFUNCTION, USING 100 MG SILDENAFIL AS A POSITIVE CONTROL. - n/a
• Scientific title: A 2-COHORT, MULTI-CENTRE, RANDOMIZED, DOUBLE BLIND (3RD PARTY OPEN), PLACEBO CONTROLLED 4-WAY CROSSOVER STUDY TO ASSESS THE EFFICACY OF SINGLE ORAL DOSES OF PF-00446687 ON ERECTILE FUNCTION IN MEN SUFFERING FROM ERECTILE DYSFUNCTION, USING 100 MG SILDENAFIL AS A POSITIVE CONTROL. - n/a
• Date of first enrolment: 25/06/2007
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001036-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: yes Other trial design description: 3rd party open If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male subjects aged 18-65 years.
2. Subjects who have given written informed consent to participate in the study.
3. Subjects must be in a heterosexual stable relationship for at least the last 6 months.
4. Subjects with erectile dysfunction of at least six months duration prior to entering the study. Erectile dysfunction is defined as “the inability to attain and/or maintain penile erection sufficient for satisfactory performance”. [protocol ref 1]
5. Subjects with moderate to severe (6-16) erectile dysfunction as classified on the International Index of Erectile Function (IIEF).
6. Subjects who, in the opinion of the investigator, are known responders to PDE5i’s, such as subjects with a current or recent (within 6 months) history of successful PDE5i use.
7. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subjects who are either known non-responders to, or unlikely to respond to treatment with either MC4 agonists or PDE5i’s. This includes subjects who are diabetic, subjects with significant neurological disease, spinal cord injury, multiple sclerosis, or previous pelvic surgery including radical and nerve sparing prostatectomy.
2. Subjects with any clinically significant abnormality, following review of pre-study
laboratory data and after a full physical examination.
3. Subjects with a history of significant cardiac disease, particularly moderate or severe cardiac failure, unstable angina or recent myocardial infarction, stroke or life-threatening arrhythmia within the previous 6 months.
4. Subjects with a history of syncope or cardiac conduction abnormality (including
paroxysmal brady or tachyarrhythmias).
5. Subjects who suffer from hypo- or hypertension (treated as well as untreated) or have a resting supine blood pressure below 90/50 mm Hg or above 170/110 or who show a postural drop in either systolic blood pressure of >20 mm Hg or diastolic blood pressure of >10 mm Hg at screening.
6. Subjects who are currently receiving vasoactive medication, such as (but not limited to) a-blockers, ß-blockers, calcium antagonists.
7. Subjects who are receiving drugs known to inhibit CYP3A4, such as ketoconazole
(systemic), erythromycin, cimetidine, clarithromycin, fluvoxamine, intraconazole
(systemic), voriconazole, protease inhibitors.
8. Subjects with any clinically significant haematological, renal or hepatic abnormality.
9. Subjects with major psychiatric disorders and those who have received treatment for any major psychiatric disorder (eg, psychosis or hospitalization due to major depression) within the past 12 months.
10. Subjects who have received any experimental (ie, non-approved) drug within the past four months (prior to the first dosing day of the study).
11. Subjects who drink more than 21 units of alcohol per week. (1 unit = 285 mL of beer or 25 mL of spirits or 125 mL of wine).
12. Subjects with a history of controlled substance abuse within the past 2 years.
13. Subjects who, in the opinion of the principal investigator, have any medical or
psychological condition or social circumstances which would impair their ability to
participate reliably in the study, or who may increase the risk to themselves or others by participating.
14. Subjects who, in the opinion of the investigator, are not likely to complete the study for whatever reason.
15. Subjects with a history of hypersensitivity to study drug and its excipients or known allergy to sildenafil and/or MC agonists.
16. Subjects with other forms of sexual dysfunction (eg, retrograde ejaculation, an
ejaculation, painful ejaculation, premature ejaculation, hypoactive sexual desire and
inhibited or absent orgasm).
17. Subjects with Peyrone’s disease.
18. Subjects with evidence or history of seizure disorder, clinically significant
haematological, renal, hepatic, psychiatric, neurologic or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
19. History of febrile illness within 5 days prior to the first dose.
20. Subjects with any condition possibly affecting drug absorption (eg, gastrectomy).
21. Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing and subjects intending to donate during the study.
22. Subjects with a 12-lead ECG demonstrating QTc >450 msec at screening.
Criteria spec

Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Male erectile dysfunction (MED).
MedDRA version: 9.1 Level: LLT Classification code 10052003 Term: Erectile dysfunction NOS

Intervention(s)

Product Name: PF-00446687
Product Code: PF-00446687
Pharmaceutical Form: Powder for oral solution
CAS Number: 662281-92-3
Current Sponsor code: PF-00446687
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 200-
Pharmaceutical form of the placebo: Powder for oral solution
Route of administration of the placebo: Oral use

Trade Name: VIAGRA ® 100 mg film-coated tablets.
Pharmaceutical Form: Tablet
INN or Proposed INN: SILDENAFIL CITRATE
CAS Number: 171,599-83-0
Current Sponsor code: UK-92,480
Other descriptive name: Viagra®
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To confirm the efficacy of single oral doses of PF-00446687 200 mg in improving penile erectile activity, utilizing the penile plethysmography (Rigiscan® Plus) technique, in males suffering from erectile dysfunction.

Secondary Objective: To establish efficacy of lower doses of PF-00446687 in improving penile erectile activity and if possible, determine the dose response, in this population.

To assess subjective assessment of sexual arousal and desire by means of questionnaire following single doses of PF-00446687.

To determine the safety and toleration of PF-00446687 in this population.

To assess PK after single doses of PF-00446687 and sildenafil in this population.

To assess Agouti Related Protein (AgRP) levels in this population.

Primary end point(s): Total duration of erections > 60% rigidity at the base of the penis and area under the rigidity response curve (AUC) of erectile activity for the duration of the post dose time sequences.
Total duration of erections > 60% rigidity at the base of the penis and AUC for the duration of (VSS-1 + VSS-2).
Total duration of erections > 60% rigidity at the base of the penis and AUC for the duration of (Neutral-1 + Neutral-2).
Duration of erections > 60% rigidity at the base of the penis and AUC at defined time sequences.
Time to onset of first erection of > 60% rigidity and a minimum of 5 minutes duration
Assessment of sexual interest and ,mental arousal .
Diary of sexual events
Exploring the dose an/or response relationship of PF-00446687.

Secondary ID(s)

A8361011

n/a