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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02232425

Enrollment

Registered

2014-09-05

Start date

2014-09-30

Completion date

2015-10-31

Last updated

2020-08-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Premature Ejaculation

Brief summary

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

Interventions

DRUGIX-01

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

MALE

Age

18 Years to 60 Years

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Proportion of Participants With Greater Than or Equal to (≥) 2.5 Fold Increase in Intravaginal Ejaculatory Latency Time (IELT)	Last 4 weeks of treatment compared to baseline	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
Mean Fold Change in Arithmetic IELT (Intravaginal Ejaculatory Latency Time)	Last 4 weeks of treatment compared to baseline	IX-01 versus placebo
Mean Change in Score on Control of Timing of Ejaculation	Last 4 weeks of treatment compared to baseline	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)
Mean Change in Score on Ejaculation-related Personal Distress	Last 4 weeks of treatment compared to baseline	Based on Premature Ejaculation Profile (PEP). Scale ranges from 'extremely' (0) to 'not at all' (4). An increase in score from baseline indicates improvement.
Proportion of Participants With ≥ 1 Category of Improvement in Satisfaction With Sexual Intercourse, on the Premature Ejaculation Profile (PEP) Questionnaire	Baseline to 8 weeks	Based on Premature Ejaculation Profile (PEP) 5 point scale with the scores ranging from 0 (worse answer) to 4 (best answer).
Proportion of Participants Rating Their PE as Better or Much Better, on the Clinical Global Impression of Change (CGIC) Scale	Baseline to the end of treatment (approximately 8 weeks)	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
Proportion of Participants With ≥ 1 Category of Improvement in Ejaculation-related Distress on the Premature Ejaculation Profile ( PEP) Questionnaire	Baseline to 8 weeks	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.
Proportion of Participants With ≥ 1 Category of Improvement in Ejaculation-related Interpersonal Difficulty on the Premature Ejaculation Profile (PEP) Questionnaire	Baseline to 8 weeks	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.
Proportion of Participants With ≥ 2 Category Increase in Control and ≥ 1 Category Decrease in Personal Distress on a Patient Reported Outcome (PRO) Measure	Baseline to 8 weeks	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)
Change in Percentage of Intercourse Attempts Lasting Longer Than 1 Minute From Baseline to Last 4 Weeks on Treatment	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.
Incidence of Treatment-emergent Adverse Events	Start of Treatment to end of study (approximately 10 weeks)	Number of participants with at least one treatment-emergent adverse event
Proportion of Participants With ≥ 1 Category of Improvement in Control Over Ejaculation During Sexual Intercourse on the Premature Ejaculation Profile (PEP) Questionnaire	Baseline to 8 weeks	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)

Countries

Australia, United States

Participant flow

Participants by arm

Arm	Count
Drug: IX-01 Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01	58
Placebo Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo	30
Total	88

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	2	0
Overall Study	Lack of Efficacy	1	0
Overall Study	Lost to Follow-up	6	2
Overall Study	Withdrawal by Subject	5	6

Baseline characteristics

Characteristic	Drug: IX-01	Total	Placebo
Age, Continuous	42 years STANDARD_DEVIATION 9	43 years STANDARD_DEVIATION 9	43 years STANDARD_DEVIATION 8
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants	12 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants	76 Participants	28 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	4 Participants	6 Participants	2 Participants
Race (NIH/OMB) Black or African American	6 Participants	11 Participants	5 Participants
Race (NIH/OMB) More than one race	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) White	48 Participants	69 Participants	21 Participants
Region of Enrollment Australia	11 participants	18 participants	7 participants
Region of Enrollment United States	47 participants	70 participants	23 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	58 Participants	88 Participants	30 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	12 / 56	9 / 30
serious Total, serious adverse events	0 / 56	0 / 30

Outcome results

Primary

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

Time frame: Last 4 weeks of treatment compared to baseline

Population: Efficacy data set excluding outliers

Arm	Measure	Value (GEOMETRIC_MEAN)
Drug: IX-01	Mean Fold Change in Geometric Mean Intravaginal Ejaculatory Latency Time (IELT)	2.1 No units for fold change
Placebo	Mean Fold Change in Geometric Mean Intravaginal Ejaculatory Latency Time (IELT)	1.1 No units for fold change

Secondary

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.

Time frame: Baseline to last 4 weeks on treatment