| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Male patients with a diagnosis of mild to moderate depression and ED as determined from the Hamilton depression scale score of 7 to 23 and International Index of Erectile Function (IIEF-5) score of 12 to 18, respectively.
Erectile dysfunction in men is the persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance. Erectile dysfunction is common in depression as part of the disease or as a consequence of antidepressant treatment. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Treatment of Erectile Dysfunction in depressed, male patients |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Reproductive physiologi cal processes [G08] |
| 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 |
| The primary objective of this study is to investigate the effects of IP2018 on penile rigidity and tumescence in male patients with a diagnosis of depression and erectile dysfunction (ED), using visual stimulation |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
• To evaluate the safety and tolerability of single oral dose levels of IP2018 in male patients with a diagnosis of depression and ED.
• To evaluate the pharmacokinetics (PK) of single oral dose levels of IP2018 in male patients with a diagnosis of depression and ED, and where possible to relate the dose response from 0.25 mg and 0.50 mg of IP2018 to efficacy. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient is male, of any ethnic origin.
2. Patient is aged between 18 to 55 years, inclusive.
3. Patient has a body mass index (BMI) of 18 to 32 mg/kg2, inclusive.
4. Patient has a score of 12 to 18 on the IIEF-5 Questionnaire at screening
5. Patient has a body weight ≥50 kg.
8. GP diagnosis of depression for over 3 months.
9. Patient is able to achieve one of the following erectile responses, based on the visual stimulus challenge conducted at screening:
• >60% base penile rigidity for >1 minute but <4 minutes, cumulatively, during the 20-minute video viewing, or
• achieve either >40% base penile rigidity for >1 minute, cumulatively, or >20% base penile rigidity for >2 minutes, cumulatively.
The visual stimulus challenge may be repeated once at the discretion of the Investigator, in consultation with the Sponsor’s Medical Doctor.
10. Mild to moderate depression, based on a score of 7 to 23 on the HAM-D at screening.
11. Aside from depression and ED, the patient is otherwise healthy as determined by a responsible physician, based on medical history, physical examinations, concomitant medication, vital signs, 12-lead ECGs, Columbia Suicide Severity Rating Scale (C-SSRS) and clinical laboratory evaluations. Laboratory values may be re-tested at the discretion of the Investigator.
Should a patient score be very high on the HAM-D or positive on the CSSRS then, if they are not already under medical care and are judged to need urgent intervention, they will be referred to Crisis Resolution Services - Crisis Care, Greater Manchester Mental Health NHS Foundation Trust.
12. Patients must use a condom from the time of first dosing until 90 days after their final dose of trial medication, if their partner is a woman of childbearing potential. In addition, their female partner of childbearing potential must use an additional method of highly effective contraception (see Section 6.3.1) 1 week prior to screening until 90 days after final dosing. |
|
| E.4 | Principal exclusion criteria |
1. Any significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal (GI), haematological, endocrinological, metabolic, neurological, psychiatric conditions, or history of fainting or syncope or such condition that, in the opinion of Investigator, may place the patient at unacceptable risk as a participant in the study, may interfere with the interpretation of safety or tolerability data obtained in this study, or may interfere with the absorption, distribution, metabolism or excretion of drugs, or with the completion of treatment according to this protocol.
2. Any history of an unstable medical or psychiatric condition (except depression) or using any medication that, in the opinion of the Investigator, is likely to affect the patient's ability to complete the study or precludes the patient's participation in the study.
3. Any presence of a condition of the genitalia which would interfere with the application of Rigiscan and interpretation of data (such as Peyronie’s disease, hypospadias, urinary catheter, genito-urinary infection).
4. Primary hypoactive sexual desire or any history of hypogonadism.
5. Any history of radical prostatectomy.
6. Patients with partners who wish to become pregnant during the course of the study.
8. Patient has any of the following on assessment of vital signs at screening or predose on Day 1 of each treatment period (vital signs may be repeated at the discretion of the Investigator):
• Supine systolic blood pressure >150 mmHg;
• Diastolic blood pressure >90 mmHg;
• Decrease in systolic blood pressure ≥20 mmHg upon standing with or without symptoms.
11. A QTc interval of >430 msec in triplicate ECGs taken at screening or a family history of Long QT syndrome.
14. History of suicidal thoughts or ideation as determined by a “yes” answer to any of the questions on the C-SSRS at any point during the previous 12 months or evidence from medical history.
16. Patients unwilling to cease use of vacuum devices, intracavernosal injection, Viagra® or other therapy for ED for the duration of the study.
20. Use of any drugs that are inhibitors or substrates of CYP2D6 and unable to stop taking them during the study, and during the 21 days before, or within 7 half-lives (whichever is longer) of dosing, until the end of the study.
25. History of gastric bypass surgery or other GI problems which could affect absorption of drug. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the duration of ≥60% rigidity and other efficacy data from RigiScan® assessments in male patients with a diagnosis of depression and ED. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Predose, and then 1, 3 and 6 hours post dose |
|
| E.5.2 | Secondary end point(s) |
The secondary endpoints are:
• The clinical safety data from AE reporting, 12-lead electrocardiograms (ECGs), vital signs (standing and supine blood pressure, heart rate and oral temperature [supine only]), physical examinations and clinical laboratory evaluations (chemistry, haematology, urinalysis) in male patients with a diagnosis of depression and ED.
• Plasma PK concentrations and parameters including but not limited to; area under the plasma concentration-time curve (AUC) from zero to the last quantifiable concentration (AUC0-t), AUC from zero to infinity (AUC0-∞), maximum plasma concentration (Cmax), time to Cmax (tmax) and half-life (t1/2) in male patients with a diagnosis of depression and ED. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Predose and then, 1, 3, 6 and 12 hours post dose
- predose and 12 hours post dose (clinical laboratory evaluations) |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| 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 | No |
| E.8.1.6 | Cross over | Yes |
| 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.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| 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 | No |
| E.8.7 | Trial has a data monitoring committee | No |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
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