E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Classification code | 10052003 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To explore the efficacy of Inhaled VR004 in Patients with Erectile Dysfunction |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Males aged between 18 and 65 years inclusively 2. Stable heterosexual relationship in which patient and partner are willing to attempt vaginal intercourse at least once per week on average during the trial 3. Patient reports having experienced ED for at least 6 months 4. Must have, in the month prior to Screening Visit 1 (Week -6), experienced an erection, which in the patient’s opinion was considered adequate for sexual intercourse, spontaneously (e.g. nocturnal, morning) or by any means including pharmacologic or device intervention 5. Patient willing and able to comply with study procedures 6. Patient will provide voluntary written informed consent.
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E.4 | Principal exclusion criteria |
1. Patients with clinically significant blood test abnormalities and previous medical history/intercurrent illnesses, which may compromise the safety of the patient in the study 2. Patients recording an IIEF Erectile Function Domain (questions 1 – 5 and 15) score ≥ 26 at Baseline 3. Patients with compromised lung function as indicated by an FEV1 value ≤ 80% predicted value or patients with a documented history of asthma or chronic obstructive pulmonary disease (COPD) 4. Significant organic disease that may adversely affect sexual function, such as radical prostatectomy, pelvic surgery, vascular or neurological disease such as multiple sclerosis (MS) or spinal cord injury 5. Myocardial infarction or stroke in the 12 months prior to screening, unstable angina or other cardiovascular condition where, in the Investigator’s opinion, sexual intercourse is contra indicated 6. Patients with uncontrolled diabetes as defined by: a. A known diabetic, not under any form of medical management, i.e. no therapeutic lifestyle (diet, exercise) changes; not on oral hypoglycaemics nor on insulin or b. HbA1c > 8% or c. Fasting plasma glucose (FPG) greater than or equal to 126 mg/dL on two occasions within the last month prior to Screening Visit 1 (Week -6) or d. Random glucose ≥ 200 mg/dL within the last month prior to Screening Visit 1 (Week -6) 7. Patients with a recorded history of postural hypotension in the previous 12 months and any patient who has a SBP of <110 mm Hg in either the sitting or standing position. Patients are also excluded if, after 3 minutes sitting, their SBP drops by more than 20 mm Hg upon standing, either immediately or after 3 minutes, or both, at Screening Visit 2 or prior to receiving study drug in the orthostatic challenge at Baseline Visit 3 8. Patients with uncontrolled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg) 9. Patients taking 5HT3 antagonists (including, for example ondansetron, granisetron, dolasetron, palonosetron and alosetron), anti-depressants, anabolic steroids, anti-androgens, anti-psychotic agents, vasodilators, nitrates, anti-emetics or apomorphine (for Parkinson’s disease), and any drug known to prolong the QT interval 10. Patients with penile prosthesis 11. Patients with a pre-disposition to priapism such as those with sickle cell disease, blood dyscrasias and multiple myeloma 12. Patients with any untreated hormonal disorders e.g. hypogonadism or hyperprolactinemia as demonstrated by high prolactin levels (>700 mIU/L) or abnormal Total testosterone (normal range 7.35 – 60.1 nmol/L) and free testosterone levels - normal ranges: Age (Years) Normal Range Units 20 to 39 8.8 – 27.0 pg/mL 40 to 59 7.2 – 23.0 pg/mL 60 to 80 5.6 – 19.0 pg/mL
If there is a discrepancy between Total and free testosterone (i.e. one normal and the other low) then the result of the free testosterone should determine the patient's eligibility. 13. Patient’s with Peyronie’s disease or congenital or trauma deformities of the penis 14. Patients with existing cancer and those in remission for less than 5 years 15. Major psychiatric disorders e.g. schizophrenia, bipolar or other major depressive illness 16. Patients previously diagnosed with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) 17. Patients with evidence as ascertained from examination, tests or history to indicate cardiovascular, gastrointestinal (GI) tract, liver, kidneys, central nervous system (CNS), pulmonary system or bone marrow disorders which in the Investigator’s opinion compromises patient safety 18. Patients who are known non-responders to apomorphine treatment for ED 19. History of drug or alcohol abuse in the 6 months prior to entry 20. Patients with a history of clinically significant allergies to VR004 formulation constituents including lactose and opioids 21. Patients who have participated in any drug study in the 3 months prior to randomisation at the Baseline Visit (Week 0, Visit 3), unless the patient had previously been enrolled in this study (VR004/003) and was withdrawn (pre-randomisation) due to suspension of the study. 22. Patients who have previously received VR004 23. In the Investigator’s opinion unsuitable for the study for any reason.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-points of this study are the change in the proportion of “yes” answers from Baseline to the last 4 weeks of study treatment in: 1. The Sexual Encounter Profile (SEP) question number 2 measuring the ability to achieve vaginal penetration 2. The SEP question number 3 measuring the ability to maintain an erection long enough for successful intercourse in patients with ED.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |