| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 |
| 1. To explore, in patients with ED of varied aetiology and disease severity, the maximum tolerated and minimally effective dose responses of VR004 by examining the efficacy and dose response at three different nominal doses (220 μg, 310 μg and 430 μg). Efficacy will be measured by the co-primary and the secondary efficacy questions. |
|
| E.2.2 | Secondary objectives of the trial |
2. To compare the efficacy of three doses of VR004 with that of placebo
3. To examine the haemodynamic safety and tolerability profile of VR004, at all tested doses, as measured by response to orthostatic challenge and the incidence and severity of spontaneously reported AEs, vital signs, lung function and abnormal laboratory test results
4. To verify the suitability of the Aspirair® inhaler in the treatment of erectile dysfunction during the at home treatment period. The mechanical robustness and the drug delivery performance of the inhaler will be verified in the laboratory by examination and testing of the returned devices at the end of the study. |
|
| 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 (inclusive)
2. Stable, heterosexual relationship in which patient and partner are willing to attempt vaginal intercourse at least once per week on average during the study
3. Patient reports having experienced ED for at least 6 months
4. Within the month prior to study Screening at Visit 1, the patient must have experienced an erection, which in the patient’s opinion was considered adequate for sexual intercourse. This can have been achieved spontaneously (e.g. nocturnal, morning) or by any means including pharmacologic
5. Subject willing and able to comply with study procedures
6. Patient will provide voluntary written informed consent.
|
|
| 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 the Baseline Visit
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 known history of glucose intolerance as defined by one of the tests below:
a. glycosylated haemoglobin (HbA1c) > 8%
or
b. Fasting plasma glucose (FPG) ≥ 126 mg/dL on two occasions within the last month prior to Screening Visit 1 (Week -6)
or
c. Random glucose ≥ 200 mg/dL within the last month prior to Screening Visit 1 (Week ?6)
7. Patients with a known propensity to postural hypotension in the previous 12 months
8. Any patient who has a SBP of < 110 mmHg 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 any point prior to receiving study drug in the Orthostatic Challenge Visit
9. Patients with untreated hypertension (sitting [not standing] SBP ≥ 160 mmHg or DBP ≥ 100 mmHg)
10. Patients taking any antihypertensive therapy, 5HT3 antagonists (including, for example ondansetron, granisetron, dolasetron, palonosetron and alosetron), anti-depressants, anabolic steroids, anti-androgens, anti-psychotic agents, vasodilators (including alpha blockers for benign prostatic hypertrophy, nitrates, anti-emetics or apomorphine (for Parkinson's disease) and any drug known to prolong the QT interval
11. Patients with penile prosthesis
12. Patients with a pre-disposition to priapism such as those with sickle cell disease, blood dyscrasias and multiple myeloma
13. Patients with any untreated hormonal disorders e.g. hypogonadism or hyperprolactinemia as demonstrated by high prolactin levels (> 700 IU/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.
14. Patient’s with Peyronie’s disease or congenital or trauma deformities of the penis
15. Patients with existing cancer and those in remission for less than 5 years
16. Major psychiatric disorders e.g. schizophrenia, bipolar or other major depressive illness
17. Patients previously diagnosed with Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS)
18. 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
19. Patients who are known non-responders to apomorphine treatment for ED
20. History of drug or alcohol abuse in the 6 months prior to entry
21. Patients with a history of clinically significant allergies to VR004 formulation constituents including lactose and opioids
22. Patients who have participated in any drug study in the 3 months prior to randomisation at the Orthostatic Challenge Visit. Note that any patient who had previously been enrolled in the VR004/003 study and was withdrawn (pre-randomisation) due to suspension of the study is eligible.
23. Patients who have previously received VR004
24. In the Investigator’s opinion unsuitable for the study for any reason. |
|
| 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.
The primary device end-points of this study are:
1. The number of devices showing any signs of unacceptable wear or damage after use
2. The in-vitro drug delivery performance of the devices, as measured by fine particle dose and delivered dose.
|
|
| 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 | Yes |
| 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) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| 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
| |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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