| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10036596 |
| E.1.2 | Term | Premature ejaculation |
|
| 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 is to determine the efficacy of dapoxetine (30/60 mg prn)
compared with placebo after 12 weeks of treatment in prolonging IELT (intravaginal ejaculatory latency time) in men with PE (premature ejaculation) and ED (erectile dysfunction) who are currently being treated with a PDE-5 inhibitor (ie, sildenafil, vardenafil, or tadalafil) for ED. |
|
| E.2.2 | Secondary objectives of the trial |
Key Secondary Objective
The key secondary objective is to assess the effect of dapoxetine (30/60 mg prn)
compared with placebo after 12 weeks of treatment on the proportion of subjects who report improvements of at least “better” in the CGIC (Clinical Global Impression of Change).
Other Secondary Objectives
The safety and tolerability of each treatment regimen (dapoxetine + PDE-5 inhibitor,
placebo + PDE-5 inhibitor) will be assessed. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Man ≥18 years of age with co-existing conditions of ED and PE
• Must have a clinical diagnosis of ED, which has been made by a clinician, and an
IIEF score ≥21 at screening and baseline to ensure reasonable erectile function during their participation in the study
• Must, by reported history, meet the following diagnostic criteria for PE, as consistent with the ISSM definition of lifelong PE, for at least 6 months before screening:
– “Ejaculation, which always or nearly always occurs prior to or within about one
minute of vaginal penetration
– Inability to delay ejaculation on all or nearly all vaginal penetrations
– Negative personal consequences, such as distress, bother, frustration, and/or the
avoidance of sexual intimacy.” For the purposes of this study negative personal
consequences are defined as distress based on the subject’s response to the
“Personal Distress” question in the PEP (Attachment 6). A subject must define his
distress level as at least “moderately”.
• Premature ejaculation must not be exclusively due to the direct effect of a substance (eg, opioid withdrawal)
• Must be using a stable regimen of a PDE-5 inhibitor (ie, sildenafil, vardenafil, or
tadalafil), as reported by the subject, for the treatment of ED for at least 3 months
before screening. A subject is considered to be using a stable regimen of a
PDE-5 inhibitor if he has been titrated to a dose that is well tolerated and provides
good erectile function (ie, an IIEF score ≥21), and the same dose has been taken on a prn basis for at least 3 months before screening. Subjects who are taking low daily
doses of tadalafil must have been taking the drug at a stable dose (ie, the same dose) for at least 3 months before screening.
• Must be in a stable, monogamous sexual relationship with the same woman for at
least 6 months before screening and plan to maintain this relationship for the duration of the study
• Subjects with a history of hypertension (including newly diagnosed hypertension)
must be adequately treated with a stable antihypertensive medical regimen for at least 2 months before screening.
• Medically stable on the basis of physical examination, medical history, vital signs,
and 12-lead ECG performed at screening. If there are abnormalities, they must be
consistent with the underlying illness in the study population.
• Medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel (including liver enzymes, other specific tests) are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the investigator.
• Women (partners) must be:
– using oral contraceptives, contraceptive injections, contraceptive patch,
intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical
cap, with spermicidal foam, cream, or gel, male partner sterilization) as local
regulations permit, or
– postmenopausal (for at least 1 year before the subject’s screening visit), or
– surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal
ligation, or otherwise be incapable of pregnancy), before entry, and must agree to continue to use the same method of contraception throughout the study (ie, if the subject and partner are using condoms before the study then they must continue to use condoms during the study).
• Women (partners) of childbearing potential must have a negative urine β-human
chorionic gonadotropin (β-hCG) pregnancy test at screening
• Men must agree to not donate sperm during the study and for 1 month after receiving the last dose of study drug.
• Willing/able to adhere to the prohibitions and restrictions specified in this protocol
• Subjects and partners must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• The subject and partner have the ability to read, speak, and understand an appropriate language for the country in which the study is being conducted. |
|
| E.4 | Principal exclusion criteria |
• Anatomical deformities of the genitals that would significantly impair an erection
(eg, Peyronie’s disease)
• Erectile dysfunction secondary to a spinal cord injury
• Penile prosthetic surgery
• Indication by the subject of a significant problem with decreased interest in sexual
intercourse or other forms of sexual dysfunction, including inhibited or absent orgasm
or ejaculation
• Sexual partner of the subject has a clinically significant problem of decreased interest in sexual intercourse, painful intercourse, or other form of female sexual dysfunction that has a significant impact on the sexual relationship with the subject
• Known or suspected hypogonadism, hyperprolactinemia, or untreated or
insufficiently treated hypothyroidism
• Significant pathologic cardiac conditions including but not limited to heart failure
(New York Heart Association [NYHA] Class II-IV cardiac disease [see Attachment 7, New York Heart Association Classification of Cardiac Disease, for a description of the classes]), conduction abnormalities (ie, second- or third-degree atrioventricular block or sick sinus syndrome) not treated with a permanent pacemaker, significant (as defined by the treating physician) ischemic heart disease, or significant valvular disease
• Hypotension, defined as a resting blood pressure <90/50 mmHg at screening
• History of untreated malignant hypertension, and/or a resting systolic blood pressure >170 mmHg, and/or a resting diastolic blood pressure of >100 mmHg
• Cerebrovascular accident or myocardial infarction within the previous 6 months
• History suggestive of syncope
• Diabetes mellitus that is poorly controlled, in the opinion of the investigator
• History of or current major psychiatric disorder such as mood disorder, anxiety
disorder, schizophrenia, mania, suicidal ideation, other psychotic disorder, or
alcoholism
• Meet the DSM-IV-TR diagnosis, in the opinion of the investigator, for a current
depressive or anxiety disorder or received treatment (whether pharmacotherapy
and/or psychotherapy) for a depressive or anxiety disorder within the past 2 years
• Positive diagnosis, based on investigator assessment of depressive or anxiety
disorder, dysthymia, suicidality, (hypo) manic episode, panic disorder, agoraphobia,
social phobia, obsessive-compulsive disorder, posttraumatic stress disorder, alcohol
abuse and dependence, non-alcohol psychoactive substance use disorder, or psychotic disorders
• History, or suspicion of the use of illicit or recreational drugs
• Known history of moderate to severe renal impairment (including dialysis) or hepatic impairment (ie, serum creatinine >1.5 times [x] the upper limit of normal [ULN], alanine aminotransferase [ALT] >1.5x ULN, aspartate aminotransferase [AST]
>1.5x ULN, total bilirubin >1.25x ULN)
• Twelve-lead ECG shows significant pathology (in the judgment of the investigator),
at screening
• History of, or currently experiencing any of the following:
– Medical events such as surgical interventions (eg, pelvic/retroperitoneal surgery),
neurologic conditions (eg, multiple sclerosis), trauma (eg, spinal cord injury), or
infections (eg, chronic prostatitis) that are associated with the onset of PE
symptoms and considered a potential cause of PE
– Bleeding disorder or retinitis pigmentosa
– Hepatitis B or C, or human immunodeficiency virus (HIV)
– Clinically significant medical or psychiatric problems, or other organ abnormality
or pathology for whom, in the opinion of the investigator, the administration of
dapoxetine would present undue risk, or interfere with study evaluations
(ie, gastrointestinal [eg, active peptic ulcer disease], pulmonary, hematologic,
neurologic [ie, poorly controlled seizures such as an occurrence of a seizure
within the previous 12 months or >2 seizures in the past 5 years], locomotor,
immunologic, ophthalmologic, metabolic, endocrine, thromboembolic [eg, history
of pulmonary embolism], rheumatologic, oncologic, renal, or hepatic disorders)
• Concomitant treatment with nitrates, androgens, or trazodone
• Known allergies, hypersensitivity, or intolerance to SSRI or selective noradrenaline
reuptake inhibitors (SNRI) compounds
• Use of medications known to be causally associated with ED within 2 weeks before
screening, or likely to need to use such medications during the study (eg, luteinizing
hormone-releasing hormone [LH-RH] analogues [ie, goserelin, triptorelin,
leuprorelin], anti-androgens)
• Have not completed the required washout period for the use of disallowed
medications before screening as defined in Attachment 2, Washout Requirements for
Selected Medications/Treatments. Subjects who are taking a disallowed medication at screening may be eligible to participate if the investigator feels, based on clinical
judgment, that it is appropriate to allow the subject to washout from a disallowed
therapy. Subjects may be rescreened 1 time only. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy variable is the average IELT at Week 12 using the LPOCF approach (Last Postbaseline Observation Carried Forward). |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| The study is considered completed with the last visit of the last subject participating in the study. |
|
| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
