IX-01 Effect on Intravaginal Ejaculatory Latency Time (IELT) and Patient Reported Outcomes in Men With Premature Ejaculation (PE)

Study Overview
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Brief Summary
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The purpose of this study is to determine the effectiveness of IX-01 in men with lifelong premature ejaculation.

Official Title
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An 8-Week, Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Effect of IX-01 on Intravaginal Ejaculatory Latency Time (IELT) and Patient Reported Outcomes in Men With Lifelong Premature Ejaculation

Conditions
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Premature Ejaculation

Intervention / Treatment
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* Drug: IX-01
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In stable (≥ 6 months) heterosexual relationship Have life-long (primary) premature ejaculation Have premature ejaculation confirmed by Intravaginal Ejaculatory Latency Time (IELT) less than or equal to (≤) 1 minute on ≥ 75% attempts at sexual intercourse Meet other aspects of the International Society for Sexual Medicine (ISSM) definition for lifelong premature ejaculation (PE), including inability to delay ejaculation on all or nearly all vaginal penetrations and negative personal consequences such as distress, bother and frustration Willing to attempt intercourse at least 4 times during run-in period and at least 8 more times during double-blind part of the study Not planning pregnancy with his partner and he is willing to use contraception (unless not of child-bearing potential, e.g., surgically sterilised) Willing to limit use of alcohol on days in which they take study drug (not more than three drinks, where one drink is defined as a 12 ounce (oz), 360 milliliter (mL) bottle of beer, a 5 oz (150 mL) glass of wine, or a 1½ oz (45 mL distilled spirits) Capable of giving written informed consent Exclusion Criteria: An Intravaginal Ejaculatory Latency Time (IELT) value ≥ 2 minutes during run-in period Less than (<) 4 attempts at sexual intercourse during run-in (screening may be extended or patient may be rescreened if there are extenuating circumstances) A rating of control of ejaculation as fair, good, or very good on the Premature Ejaculation Profile (PEP) questionnaire prior to study Co-existing Erectile Dysfunction - International Index of Erectile Dysfunction (IIEF) erectile function domain < 22 during run-in Concomitant use of Phosphodiesterase 5 (PDE5) inhibitors, intracavernosal injections, penile implants, Selective Serotonin Reuptake Inhibitors (SSRI's) or Serotonin-Norepinephrine Reuptake Inhibitors (SSNRI's), tricyclic antidepressants (for example (e.g.) clomipramine), monoamine oxidase inhibitors, alpha blockers, 5 alpha reductase inhibitors (including propecia for hair loss), topical anaesthetics, and/or tramadol History (last 6 months) of use of Botox or similar product to treat premature ejaculation Unwilling to stop other treatments for premature ejaculation (including but not limited to pharmacological, herbal, multiple condoms, psychosexual treatment, prior masturbation) Other sexual disorder of patient or partner that could interfere with results Current active sexually transmitted disease Major medical condition of patient that could interfere with ability to have sexual activity and or require hospital treatment Body Mass Index (BMI) > 40 kg/m2 Participation in a clinical drug trial anytime during the 30 days prior to screening Human Immunodeficiency Virus (HIV) or hepatitis B History of clinically significant prostate disease History of myocardial infarction, coronary bypass surgery, coronary artery angioplasty, unstable angina, clinically evident congestive heart failure, cardiac pacemaker, or cerebrovascular accident Cardiac arrhythmia: significant cardiac arrhythmia shown on Electrocardiogram (ECG), or a known or suspected history of significant cardiac arrhythmias within last six months History of congenital QT prolongation and/ corrected QT (QTc) interval > 450 milliseconds (msec) using the Bazett formula Mean systolic cuff blood pressure (BP) > 140 millimeter of mercury (mmHg), as assessed by up to three measurements taken in sequence within 5-10 minutes of last measure Mean diastolic cuff BP > 90 mmHg, as assessed by up to three measurements taken in sequence within 5-10 minutes of the last measure Major psychiatric disease or risk of suicidal tendency as assessed by clinical evaluation and Patient Health Questionnaire (PHQ)-9 and Columbia Suicide Assessment PHQ-9 questionnaire total score > 9 and/or score > 0 for question 9 of PHQ-9, and/or suicidal ideation or behavior as assessed by Columbia Suicide Assessment Clinically significant abnormal laboratory function test results (including liver enzymes > 2 x Upper Limit of Normal (ULN) or bilirubin > 1.5 x ULN) Taking Cytochrome P450 3A4 (CYP3A4) inducers, or moderate and potent CYP3A4 inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug: IX-01<br>Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity | Drug: IX-01<br> <br> |
| Placebo Comparator: Placebo<br>Two to four capsules administered orally, 1-6 hours prior to sexual activity | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Fold Change in Geometric Mean Intravaginal Ejaculatory Latency Time (IELT) | IX-01 versus placebo. Intravaginal ejaculatory latency time (IELT) was defined as the time from the initiation of sexual intercourse (penetration) until ejaculation occurred | Last 4 weeks of treatment compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Rating Their PE as Better or Much Better, on the Clinical Global Impression of Change (CGIC) Scale | 7 point scale ranging from much worse (-3) to much better (3). The proportion refers to the proportion of patients who had the best 2 possible responses [better(2) or much better (3)] on this 7 point scale | Baseline to the end of treatment (approximately 8 weeks) | 
| Proportion of Participants With Greater Than or Equal to (≥) 2.5 Fold Increase in Intravaginal Ejaculatory Latency Time (IELT) | Intravaginal ejaculatory latency time (IELT) was defined as the time from the initiation of sexual intercourse (penetration) until ejaculation occurred. Outcome measured proportion of patients with at least a 2.5-fold increase in geometric mean IELT over the last 4 weeks of treatment as compared to baseline. Proportion of participants adjusted for baseline IELT, country and site | Last 4 weeks of treatment compared to baseline | 
| Mean Fold Change in Arithmetic IELT (Intravaginal Ejaculatory Latency Time) | IX-01 versus placebo | Last 4 weeks of treatment compared to baseline | 
| Mean Change in Score on Control of Timing of Ejaculation | Reported in electronic diary and based on the Premature Ejaculation Profile (PEP). PEP question on control of timing is scored on a 5 point scale with the scores ranging from very poor (this is the worst answer) scored as 0 to very good (this is the best answer scored as 4) | Last 4 weeks of treatment compared to baseline | 
| Mean Change in Score on Ejaculation-related Personal Distress | Based on Premature Ejaculation Profile (PEP). Scale ranges from 'extremely' (0) to 'not at all' (4). An increase in score from baseline indicates improvement. | Last 4 weeks of treatment compared to baseline | 
| Proportion of Participants With ≥ 1 Category of Improvement in Satisfaction With Sexual Intercourse, on the Premature Ejaculation Profile (PEP) Questionnaire | Based on Premature Ejaculation Profile (PEP) 5 point scale with the scores ranging from 0 (worse answer) to 4 (best answer). | Baseline to 8 weeks | 
| Proportion of Participants With ≥ 1 Category of Improvement in Control Over Ejaculation During Sexual Intercourse on the Premature Ejaculation Profile (PEP) Questionnaire | Reported in electronic diary and based on the Premature Ejaculation Profile (PEP). PEP is scored on a 5 point scale with the scores ranging from 0 (worst answer) to 4 (best answer) | Baseline to 8 weeks | 
| Proportion of Participants With ≥ 1 Category of Improvement in Ejaculation-related Distress on the Premature Ejaculation Profile ( PEP) Questionnaire | Reported in e-diary. Based on Premature Ejaculation Profile (PEP). Scale ranges from 'extremely' (0) to 'not at all' (4). An increase in score from baseline indicates improvement. | Baseline to 8 weeks | 
| Proportion of Participants With ≥ 1 Category of Improvement in Ejaculation-related Interpersonal Difficulty on the Premature Ejaculation Profile (PEP) Questionnaire | Reported in e-diary. Based on Premature Ejaculation Profile (PEP). Scale ranges from 'extremely' (0) to 'not at all' (4). An increase in score from baseline indicates improvement. | Baseline to 8 weeks | 
| Proportion of Participants With ≥ 2 Category Increase in Control and ≥ 1 Category Decrease in Personal Distress on a Patient Reported Outcome (PRO) Measure | Reported in e-diary. Based on Premature Ejaculation Profile (PEP). Each of the PEP questions is scored on a 5 point scale with the scores ranging from 0 (worst answer) to 4 (best answer) | Baseline to 8 weeks | 
| Change in Percentage of Intercourse Attempts Lasting Longer Than 1 Minute From Baseline to Last 4 Weeks on Treatment | 'Baseline' time period defined as Day -28 - Day 0. 'Last 4 Weeks' time period defined as the 28 days prior to last time subject took study drug and after Day 14. Analysis excludes two subjects from ITT population: #010-012 (placebo) and #888-018 (active). Adjusted for treatment, baseline IELT, baseline percentage, country and site. | Baseline to last 4 weeks on treatment | 
| Incidence of Treatment-emergent Adverse Events | Number of participants with at least one treatment-emergent adverse event | Start of Treatment to end of study (approximately 10 weeks) |