IX-01 Effect on Intravaginal Ejaculatory Latency Time (IE... | NCT02232425

Status Module

Name	Class
Carelon Research	OTHER
Novotech (Australia) Pty Limited	INDUSTRY
ICON plc	INDUSTRY
PHT Corporation

Label	Type	Description	Intervention Names
Drug: IX-01	Experimental	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity	Drug: IX-01
Placebo	Placebo Comparator	Two to four capsules administered orally, 1-6 hours prior to sexual activity	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
IX-01	Drug		Drug: IX-01
Placebo

Outcomes Module

Primary Outcomes

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 Outcomes

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)

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Email Katie.George@Ixchelsis.com	Ixchelsis Limited	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
San Diego Sexual Medicine		San Diego	California	92120	United States
South Florida Medical Research Inc.

PubMed Identifier	Type	Citation	Retractions
31351659	Derived	McMahon C, Althof S, Rosen R, Giuliano F, Miner M, Osterloh IH, Muirhead GJ, Harty B; PEPIX Multi-Centre Study Group. The Oxytocin Antagonist Cligosiban Prolongs Intravaginal Ejaculatory Latency and Improves Patient-Reported Outcomes in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Trial (PEPIX). J Sex Med. 2019 Aug;16(8):1178-1187. doi: 10.1016/j.jsxm.2019.05.016.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
FG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
BG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00058 BG00130 BG00288

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

Efficacy data set excluding outliers

Posted

Geometric Mean

95% Confidence Interval

No units for fold change

Last 4 weeks of treatment compared to baseline

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG00054 OG00125

Title

Denominators

Categories

Title	Measurements
	OG0002.1(1.5 to 3.1) OG0011.1(0.7 to 1.8)

Secondary

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

Intent to treat, excluding outliers

Posted

Number

proportion of participants

Baseline to the end of treatment (approximately 8 weeks)

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Secondary

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

Intent to treat, excluding outliers

Posted

Number

95% Confidence Interval

Proportion of participants

Last 4 weeks of treatment compared to baseline

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Secondary

Mean Fold Change in Arithmetic IELT (Intravaginal Ejaculatory Latency Time)

IX-01 versus placebo

Intent to treat, excluding outliers

Posted

Mean

95% Confidence Interval

No units for fold change

Last 4 weeks of treatment compared to baseline

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Secondary

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)

Intent to treat, excluding outliers

Posted

Mean

95% Confidence Interval

units on a scale

Last 4 weeks of treatment compared to baseline

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Secondary

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.

Intent to treat, excluding outliers

Posted

Mean

95% Confidence Interval

units on a scale

Last 4 weeks of treatment compared to baseline

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Secondary

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).

Intent to treat, excluding outliers

Posted

Number

95% Confidence Interval

adjusted proportion of participants

Baseline to 8 weeks

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Secondary

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)

Intent to treat, excluding outliers

Posted

Number

95% Confidence Interval

adjusted proportion of participants

Baseline to 8 weeks

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Secondary

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.

Intent to treat, excluding outliers

Posted

Number

95% Confidence Interval

adjusted proportion of participants

Baseline to 8 weeks

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Secondary

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.

Intent to treat, excluding outliers

Posted

Number

95% Confidence Interval

adjusted proportion of participants

Baseline to 8 weeks

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Secondary

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)

Intent to treat, excluding outliers

Posted

Number

proportion of participants

Baseline to 8 weeks

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

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.

Intent to treat, excluding outliers

Posted

Mean

95% Confidence Interval

percentage of attempts

Baseline to last 4 weeks on treatment

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Secondary

Incidence of Treatment-emergent Adverse Events

Number of participants with at least one treatment-emergent adverse event

Intent to treat, excluding outliers

Posted

Number

participants

Start of Treatment to end of study (approximately 10 weeks)

ID	Title	Description
OG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01
OG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Ear Pain	Ear and labyrinth disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected56 at risk EG0011 affected30 at risk
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected56 at risk EG0011 affected30 at risk
Dry Mouth	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0011 affected30 at risk
Dental caries	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk
Diarrhea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected56 at risk EG0011 affected30 at risk
Hemorrhoids	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected56 at risk EG0011 affected30 at risk
Peridontal inflammation	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk
Feeling jittery	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected56 at risk EG0011 affected30 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0012 affected30 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected56 at risk EG0011 affected30 at risk
Skin infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk
Tooth abscess	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected56 at risk EG0011 affected30 at risk
Lacerations	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected56 at risk EG0011 affected30 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0011 affected30 at risk
Hepatic enzyme increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk
Laboratory test abnormal	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk
Metabolic function test abnormal	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk
Paraesthesia	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk
Libido decreased	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk
Renal Colic	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected56 at risk EG0011 affected30 at risk
Rhinitis, allergic	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected56 at risk EG0011 affected30 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected56 at risk EG0010 affected30 at risk

ID	Term
D000097910	Ejaculatory Dysfunction
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D012735	Sexual Dysfunction, Physiological
D052801	Male Urogenital Diseases
D020018	Sexual Dysfunctions, Psychological
D001523	Mental Disorders

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Drug: IX-01	Two to four 200 mg capsules administered orally, 1-6 hours prior to sexual activity IX-01			0	56	12	56
EG001	Placebo	Two to four capsules administered orally, 1-6 hours prior to sexual activity Placebo			0	30	9	30