A Study of Ejaculatory Dysfunction in Men With Low Testosterone Levels

• ClinicalTrials.gov Identifier: NCT01419236
• Recruitment Status: Completed
• First Posted: August 18, 2011
• Results First Posted: December 19, 2014
• Last Update Posted: December 19, 2014
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The purpose of this study is to see if testosterone solution 2% can impact symptoms of ejaculatory dysfunction in men with low testosterone.

Condition or disease	Intervention/treatment	Phase
Ejaculatory Dysfunction; Hypogonadism	Drug: Testosterone Solution 2%; Drug: Placebo Solution	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Study to Explore the Impact of Testosterone Solution 2% on Symptoms of Ejaculatory Dysfunction in Men With Testosterone Deficiency
• Study Start Date: August 2011
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Testosterone Solution 2% 60 milligrams (mg); Testosterone Solution 2% 60 mg applied topically once daily with possible 1-time titration to 30 milligrams per day (mg/day) or 90 mg/day for 16 weeks	Drug: Testosterone Solution 2%; Administered topically; Other Names: Axiron; LY900011
Placebo Comparator: Placebo; Placebo solution applied topically once daily for 16 weeks	Drug: Placebo Solution; Administered topically

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in the Male Sexual Health Questionnaire-Ejaculatory Dysfunction-Short Form (MSHQ-EjD-SF) Ejaculatory Function Score at 16 Weeks [ Time Frame: Baseline, 16 weeks ]
   MSHQ-EjD-SF: 4 item, self-reported questionnaire assessing ejaculatory dysfunction. MSHQ-EjD-SF Ejaculatory Function Score: sum of scores for questions (Q)1 through Q3 about frequency and strength of ejaculations and volume of ejaculate for sexual activity attempts during past month. Ejaculation frequency was rated 1 (could not ejaculate) to 5 (all the time); strength and volume from 0 (could not ejaculate) to 5 (as strong/much as it always has been). Total Ejaculatory Function Score ranged from 1 to 15. Least-squares (LS) mean of change from baseline calculated using repeated measures mixed-effects model (MMRM) including treatment, visit, treatment-by-visit interaction, region, baseline total testosterone level [≥200 nanograms per deciliter (ng/dL) versus (vs.) <200 ng/dL], baseline erectile dysfunction (ED) severity (normal, mild, moderate, severe), and centered baseline ejaculatory function score as fixed effects, and unstructured covariance structure for modeling correlation.

Secondary Outcome Measures :

1. Change From Baseline in Ejaculate Volume at 16 Weeks [ Time Frame: Baseline, 16 weeks ]
   The change from baseline in ejaculate volume was determined by actual measurement of semen volume in milliliters (mL). LS mean of change from baseline was calculated using MMRM including treatment, visit, treatment-by-visit interaction, region, baseline total testosterone level (≥200 ng/dL vs. <200 ng/dL), baseline ED severity (normal, mild, moderate, severe), and centered baseline ejaculatory volume as fixed effects, and unstructured covariance structure for modeling correlation.
2. Change From Baseline in Sexual Activity Log: Perceived Volume of Ejaculate at 16 Weeks [ Time Frame: Baseline, 16 weeks ]
   The sexual activity log was used by study participants to document ejaculatory functioning and orgasmic pleasure for each sexual activity attempt over 4 weeks. Ejaculatory functioning included perceived volume of ejaculate, perceived force of ejaculation, delayed ejaculation, and frequency. Reported is the perceived volume of ejaculate rated from 0 (no ejaculate) to 10 (high volume of ejaculate). LS mean of change from baseline was calculated using MMRM including treatment, visit, treatment-by-visit interaction, region, baseline total testosterone level (≥200 ng/dL vs. <200 ng/dL), baseline ED severity (normal, mild, moderate, severe), and centered baseline ejaculatory volume as fixed effects, and unstructured covariance structure for modeling correlation.
3. Change From Baseline in Sexual Activity Log: Perceived Force of Ejaculation at 16 Weeks [ Time Frame: Baseline, 16 weeks ]
   The sexual activity log was used by study participants to document ejaculatory functioning and orgasmic pleasure for each sexual activity attempt over 4 weeks. Ejaculatory functioning included perceived volume of ejaculate, perceived force of ejaculation, delayed ejaculation, and frequency. Reported is the perceived force of ejaculation rated from 0 (could not ejaculate) to 10 (strong ejaculation). LS mean of change from baseline was calculated using MMRM including treatment, visit, treatment-by-visit interaction, region, baseline total testosterone level (≥200 ng/dL vs. <200 ng/dL), baseline ED severity (normal, mild, moderate, severe), and centered baseline perceived force of ejaculation as fixed effects, and unstructured covariance structure for modeling correlation.
4. Change From Baseline in Sexual Activity Log: Delayed Ejaculation at 16 Weeks [ Time Frame: Baseline, 16 weeks ]
   The sexual activity log was used by study participants to document ejaculatory functioning and orgasmic pleasure for each sexual activity attempt over 4 weeks. Ejaculatory functioning included perceived volume of ejaculate, perceived force of ejaculation, delayed ejaculation, and frequency. Reported is delayed ejaculation rated from 0 (did not ejaculate) to 10 (optimal/best ejaculate time). LS mean of change from baseline was calculated using MMRM including treatment, visit, treatment-by-visit interaction, region, baseline total testosterone level (≥200 ng/dL vs. <200 ng/dL), baseline ED severity (normal, mild, moderate, severe), and centered baseline delayed ejaculation as fixed effects, and unstructured covariance structure for modeling correlation.
5. Change From Baseline in Sexual Activity Log: Frequency of Sexual Attempts at 16 Weeks [ Time Frame: Baseline, up to 16 weeks ]
   The sexual activity log was used by study participants to document ejaculatory functioning and orgasmic pleasure for each sexual activity attempt over 4 weeks. Ejaculatory functioning included perceived volume of ejaculate, perceived force of ejaculation, delayed ejaculation, and frequency. Reported is the change from baseline number of sexual attempts at 16 weeks. LS mean of change from baseline was calculated using an analysis of covariance (ANCOVA) including treatment group, region, baseline total testosterone level, baseline ED severity (normal, mild, moderate, severe) as fixed effects, and centered baseline as a covariate.
6. Change From Baseline in Sexual Activity Log: Orgasmic Pleasure at 16 Weeks [ Time Frame: Baseline, 16 weeks ]
   The sexual activity log was used by study participants to document ejaculatory functioning and orgasmic pleasure for each sexual activity attempt over 4 weeks. Reported is orgasmic pleasure rated from 0 (no pleasure) to 10 (excellent). LS mean of change from baseline was calculated using MMRM including treatment, visit, treatment-by-visit interaction, region, baseline total testosterone level (≥200 ng/dL vs. <200 ng/dL), baseline ED severity (normal, mild, moderate, severe), and centered baseline orgasmic pleasure as fixed effects, and unstructured covariance structure for modeling correlation.
7. Change From Baseline in the International Index of Erectile Function (IIEF)-Orgasmic Function Domain Score at 16 Weeks [ Time Frame: Baseline, 16 weeks ]
   IIEF: 15 item, self-reported questionnaire assessing overall erectile function and satisfaction during past month. Orgasmic Function Domain Score: sum of IIEF scores for Q9 and Q10. In Q9, participants (pts) identified how often they ejaculated when having sexual stimulation or intercourse. In Q10, pts identified how often they had a feeling of an orgasm with or without ejaculation when having sexual stimulation or intercourse. For each Q, scores ranged from 0 (no sexual stimulation or intercourse), 1 (almost never or never) to 5 (almost always or always). Total Orgasmic Function Domain Scores ranged from 0 to 10. LS mean of change from baseline calculated using MMRM including treatment, visit, treatment-by-visit interaction, region, baseline total testosterone level (≥200 ng/dL vs. <200 ng/dL), baseline ED severity (normal, mild, moderate, severe), and centered baseline Orgasmic Function Domain Score as fixed effects, and unstructured covariance structure for modeling correlation.
8. Change From Baseline in MSHQ-EjD-SF Bother/Satisfaction Score at 16 Weeks [ Time Frame: Baseline, 16 weeks ]
   The MSHQ-EjD-SF was a 4 item, self-reported questionnaire used for the assessment of EjD during the past month. The MSHQ-EjD-SF Bother/Satisfaction Score was based on Q4: "If you have had any ejaculation difficulties or have been unable to ejaculate, have you been bothered by this?" Scores ranged from 0 (no problem with ejaculation), 1 (not at all bothered) to 5 (extremely bothered). LS mean of change from baseline was calculated using MMRM including treatment, visit, treatment-by-visit interaction, region, baseline total testosterone level (≥200 ng/dL vs. <200 ng/dL), baseline ED severity (normal, mild, moderate, severe), and centered baseline Bother/Satisfaction Score as fixed effects, and unstructured covariance structure for modeling correlation.

Eligibility Criteria

• Ages Eligible for Study: 26 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Total testosterone level <10.4 nanomoles per liter (nmol/L) [300 nanograms per deciliter (ng/dL)] at screening
• Presents with 1 or more of the following symptom(s) of ejaculatory dysfunction: delayed ejaculation, anejaculation, decreased force of ejaculation, or decreased ejaculatory volume, as determined by investigator assessment
• Prostate-Specific Antigen (PSA) <4 nanograms per milliliter (ng/mL) at screening

Exclusion Criteria:

• Sexual partner who is or becomes pregnant at any time during the study
• Premature ejaculation as determined by investigator assessment
• Currently receiving testosterone replacement therapy or have a history of insufficient response to testosterone replacement therapy for ejaculatory dysfunction symptoms
• Currently receiving treatment with cancer chemotherapy or antiandrogens
• History of use of estrogenizing agents
• Current use of warfarin
• History of selective serotonin reuptake inhibitor (SSRI) and/or serotonin-norepinephrine reuptake inhibitor (SNRI) treatment in the 6 months prior to screening
• History of frequent opioid use within 30 days prior to screening, with exception of treatment for chronic pain as determined by investigator.
• Body Mass Index (BMI) >35 kilograms per square meter (kg/m^2) at screening
• Significant peripheral neuropathy affecting erectile, ejaculatory, or orgasmic function
• Hematocrit ≥50% at screening
• Exhibit systolic blood pressure >170 millimeters of mercury (mm Hg) or <90 mm Hg or diastolic blood pressure >100 mm Hg or <50 mm Hg at screening (if stress is suspected, retest under basal conditions at screening), or have history of malignant hypertension
• History of any of the following coronary conditions within 90 days of screening: myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention (for example, angioplasty or stent placement)
• Known or suspected carcinoma (or history of carcinoma) of the prostate or suspicious nodules on digital rectal exam at screening
• Known or suspected breast cancer (or history of breast cancer) or other active cancer (with the exception of nonmelanotic skin cancer)

Contacts and Locations

Locations

United States, California

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Los Angeles, California, United States, 90048

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

San Diego, California, United States, 92120

United States, Louisiana

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

New Orleans, Louisiana, United States, 70112

United States, Massachusetts

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Brookline, Massachusetts, United States, 02445

United States, New York

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Great Neck, New York, United States, 11021

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

New York, New York, United States, 10021

Canada, Quebec

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Quebec City, Quebec, Canada, G1N 4V3

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Paduch DA, Polzer PK, Ni X, Basaria S. Testosterone Replacement in Androgen-Deficient Men With Ejaculatory Dysfunction: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2015 Aug;100(8):2956-62. doi: 10.1210/jc.2014-4434. Epub 2015 Jul 9.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01419236
• Other Study ID Numbers: 13981; I5E-MC-TSAB ( Other Identifier: Eli Lilly and Company )
• First Posted: August 18, 2011
• Results First Posted: December 19, 2014
• Last Update Posted: December 19, 2014
• Last Verified: December 2014

Keywords provided by Eli Lilly and Company:

Ejaculatory Dysfunction; Orgasmic Dysfunction; Sexual Dysfunction; Climax Dysfunction; Erectile Dysfunction; Impotence; Hypogonadism; Low testosterone; Low t

Additional relevant MeSH terms:

Hypogonadism; Gonadal Disorders; Endocrine System Diseases; Pharmaceutical Solutions; Testosterone; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs