Treatment Outcome
Conditions
Keywords
Sexual Dysfunction, Physiological, Depressive Disorder, Major, Depression, Antidepressive Agents, Drug Therapy
Brief summary
The purpose of this study is to evaluate the effects of Vortioxetine (Lu AA21004), once daily (QD), compared with escitalopram on sexual functioning.
Detailed description
The drug being tested in this study is called Lu AA21004. Lu AA21004 is being tested to treat people who have major depressive disorder (MDD). This study will look at sexual function in people who take Lu AA21004. The study will enroll approximately 440 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): * Lu AA21004 10 to 20 mg * Escitalopram 10 to 20 mg - This is a comparator drug that is also used to treat MDD. All participants will be asked to take one tablet at the same time each day throughout the study. All participants will be asked to answer questionnaires at each study visit. This multi-centre trial will be conducted in the United States and Canada. The overall time to participate in this study is 14 weeks. Participants will make 7 visits to the clinic, and will be contacted by telephone 21 days after last dose of study drug for a follow-up assessment.
Interventions
DRUGVortioxetine
Vortioxetine tablets
DRUGEscitalopram
Escitalopram tablets
DRUGPlacebo
Vortioxetine Placebo-matching capsules
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Is a man or a woman aged between 18 and 55 years, inclusive, who is currently being treated with selective serotonin reuptake inhibitor (SSRI) monotherapy (only citalopram, paroxetine, or sertraline allowed) for at least 8 weeks, which was prescribed to treat a major depressive episode (MDE), according to the DSM-IV-TR criteria. 2. Is currently stable; and has a Clinical Global Impression Scale-Severity of Illness Scale (CGI-S) score of ≤3. 3. Is currently experiencing treatment-emergent sexual dysfunction (TESD; defined as a Changes in Sexual Functioning Questionnaire (CSFQ-14) total score ≤41 for women and ≤47 for men), considered to be attributable to the current SSRI monotherapy and is suitable for a switch.
Exclusion criteria
1. Has previously participated in a Lu AA21004 clinical study. 2. Has 1 or more the following: any current psychiatric disorder other than MDD as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR; as assessed by the Mini International Neuropsychiatric Interview Version 6.0.0); current or history of manic or hypomanic episode, schizophrenia, or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR; current diagnosis of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least 2 years prior to Screening (subject must also have negative urine drug screen prior to Baseline); presence or history of a clinically significant neurological disorder (including epilepsy); neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc); or any Axis II disorder that might compromise the study. 3. Has sexual dysfunction associated with an etiology other than SSRI treatment or current MDE (e.g., due to a medical condition, such as diabetes or hypertension, a medication, a genital anatomical deformity, or alcohol abuse). 4. Is nonsexually active or anticipates decreasing frequency of sexual activity (ie, sexual activity anticipated to lead to orgasm or that would normally lead to orgasm, which can include sexual intercourse, oral sex, masturbation, sexual fantasies, and/or thinking of sexual activity) during the course of the study below the level at study initiation. 5. Is a male with a history of premature ejaculation in the past year. 6. Has had major relationship changes during the preceding SSRI treatment period or plans to have major relationship changes during the course of the study. 7. Has a sexual partner(s) who plans to initiate treatment for sexual dysfunction during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14) Total Score at Week 8 | Baseline, Week 8 | The CSFQ-14 is a structured self reported questionnaire designed to measure illness- and medication-related changes in sexual functioning consisting of 14 items that measure sexual functioning as a total score (14 items) and on the subscales of pleasure (1 item), desire/frequency (2 items), desire/interest (3 items), arousal (3 items), and orgasm (3 items), rated on an 5 point scale from 1 to 5 with a total score range from 14 to 70. Higher scores reflect higher sexual functioning. A positive change from Baseline indicates that symptoms have improved. The primary analysis was based on a mixed model for repeated measurements (MMRM) analysis of covariance with treatment, center, week, treatment-by-week interaction as fixed effects, Baseline CSFQ-14 total score-by-week as covariate, and a completely unstructured covariance matrix. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed | Baseline and Weeks 1, 2, 4 and 6 | The CSFQ-14 is a structured self reported questionnaire designed to measure illness- and medication-related changes in sexual functioning consisting of 14 items that measure sexual functioning as a total score (14 items) and on the subscales of pleasure (1 item), desire/frequency (2 items), desire/interest (3 items), arousal (3 items), and orgasm (3 items), rated on an 5 point scale from 1 to 5 with a total score range from 14 to 70. Higher scores reflect higher sexual functioning. A positive change from Baseline indicates that symptoms have improved. The primary analysis was based on a mixed model for repeated measurements (MMRM) analysis of covariance with treatment, center, week, treatment-by-week interaction as fixed effects, Baseline CSFQ-14 total score-by-week as covariate, and a completely unstructured covariance matrix. |
| Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Baseline and Weeks 1, 2, 4, 6 and 8 | The CSFQ-14 is a structured self reported questionnaire designed to measure illness- and medication-related changes in sexual functioning consisting of 14 items that measure sexual functioning as a total score (14 items) and on the subscales of pleasure (1 item), desire/frequency (2 items), desire/interest (3 items), arousal (3 items), and orgasm (3 items), rated on an 5 point scale from 1 to 5 with a total score range from 14 to 70. Higher scores reflect higher sexual functioning. Normal sexual functioning is defined as a CSFQ-14 total score of \>41 for women and \>47 for men. Abnormal sexual functioning is defined as a CSFQ-14 total score of ≤41 for women and ≤47 for men. All subjects entered the study with abnormal sexual functioning. A shift to normal indicates that symptoms have improved. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants took part in the study at 57 sites in the US and 9 sites in Canada from 16 June 12011 to 9 December 2013.
Pre-assignment details
Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 2 (flexible doses of either vortioxetine (Lu AA21004) 10/20 mg once daily (QD) or escitalopram 10/20 mg QD) treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Vortioxetine Vortioxetine 10 mg, tablets, orally, once daily for 1 week, then dose adjustment to a maximum 20 mg tablets, orally, once daily for up to 7 weeks. At week 8, vortioxetine placebo-matching capsules, orally, once daily for 1 week only. | 225 |
| Escitalopram Escitalopram 10 mg, tablets, orally, once daily for 1 week, then escitalopram dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks. At week 8, escitalopram 10 mg, capsules, capsules, orally, once daily for 1 week only | 222 |
| Total | 447 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 6 | 0 |
| Overall Study | Lost to Follow-up | 12 | 13 |
| Overall Study | Non-compliance with Investigational Drug | 1 | 0 |
| Overall Study | Other | 4 | 1 |
| Overall Study | Pretreatment Event or Adverse Event | 20 | 14 |
| Overall Study | Protocol Deviations | 4 | 8 |
| Overall Study | Withdrawal of Consent | 9 | 7 |
Baseline characteristics
| Characteristic | Escitalopram | Vortioxetine | Total |
|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 10.01 | 39.3 years STANDARD_DEVIATION 9.96 | 39.8 years STANDARD_DEVIATION 9.98 |
| Age, Customized ≤41 years | 112 participants | 122 participants | 234 participants |
| Age, Customized >41 years | 110 participants | 103 participants | 213 participants |
| Alcohol Consumption 2 to 6 times per week | 36 participants | 33 participants | 69 participants |
| Alcohol Consumption Daily | 2 participants | 1 participants | 3 participants |
| Alcohol Consumption Never | 65 participants | 65 participants | 130 participants |
| Alcohol Consumption Once a week | 37 participants | 40 participants | 77 participants |
| Alcohol Consumption Once monthly or less often | 82 participants | 86 participants | 168 participants |
| Body Mass Index (BMI) | 27.90 kg/m^2 STANDARD_DEVIATION 4.44 | 27.54 kg/m^2 STANDARD_DEVIATION 4.352 | 27.72 kg/m^2 STANDARD_DEVIATION 4.395 |
| Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14) Total Score | 36.3 scores on a scale STANDARD_DEVIATION 5.62 | 36.5 scores on a scale STANDARD_DEVIATION 5.81 | 36.4 scores on a scale STANDARD_DEVIATION 5.71 |
| Clinical Global Impression - Severity scale (CGI-S) score | 2.0 scores on a scale STANDARD_DEVIATION 0.84 | 2.0 scores on a scale STANDARD_DEVIATION 0.81 | 2.0 scores on a scale STANDARD_DEVIATION 0.82 |
| Height | 170.3 cm STANDARD_DEVIATION 8.81 | 169.6 cm STANDARD_DEVIATION 9.73 | 169.9 cm STANDARD_DEVIATION 9.28 |
| Montgomery Åsberg Depression Rating Scale (MADRS) total score | 8.3 scores on a scale STANDARD_DEVIATION 6.53 | 7.9 scores on a scale STANDARD_DEVIATION 6.28 | 8.1 scores on a scale STANDARD_DEVIATION 6.4 |
| Profile of Mood States (POMS) Brief Total Score | 19.7 scores on a scale STANDARD_DEVIATION 19.45 | 18.8 scores on a scale STANDARD_DEVIATION 19.36 | 19.2 scores on a scale STANDARD_DEVIATION 19.39 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Asian | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized Black of African American | 35 participants | 41 participants | 76 participants |
| Race/Ethnicity, Customized Caucasian (or White, including Hispanic) | 181 participants | 178 participants | 359 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 36 participants | 14 participants | 50 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Non-Hispanic and Non-Latino | 186 participants | 211 participants | 397 participants |
| Region of Enrollment North America | 222 participants | 225 participants | 447 participants |
| Sex: Female, Male Female | 135 Participants | 128 Participants | 263 Participants |
| Sex: Female, Male Male | 87 Participants | 97 Participants | 184 Participants |
| Smoking Classification Current smoker | 55 participants | 69 participants | 124 participants |
| Smoking Classification Ex-smoker | 41 participants | 44 participants | 85 participants |
| Smoking Classification Never smoked | 126 participants | 112 participants | 238 participants |
| Waist Circumference | 93.31 cm STANDARD_DEVIATION 13.074 | 90.85 cm STANDARD_DEVIATION 13.274 | 92.07 cm STANDARD_DEVIATION 13.218 |
| Weight | 81.22 kg STANDARD_DEVIATION 16.012 | 79.62 kg STANDARD_DEVIATION 16.202 | 80.41 kg STANDARD_DEVIATION 16.11 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 90 / 224 | 60 / 221 |
| serious Total, serious adverse events | 3 / 224 | 1 / 221 |
Outcome results
Primary
Change From Baseline in the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14) Total Score at Week 8
The CSFQ-14 is a structured self reported questionnaire designed to measure illness- and medication-related changes in sexual functioning consisting of 14 items that measure sexual functioning as a total score (14 items) and on the subscales of pleasure (1 item), desire/frequency (2 items), desire/interest (3 items), arousal (3 items), and orgasm (3 items), rated on an 5 point scale from 1 to 5 with a total score range from 14 to 70. Higher scores reflect higher sexual functioning. A positive change from Baseline indicates that symptoms have improved. The primary analysis was based on a mixed model for repeated measurements (MMRM) analysis of covariance with treatment, center, week, treatment-by-week interaction as fixed effects, Baseline CSFQ-14 total score-by-week as covariate, and a completely unstructured covariance matrix.
Time frame: Baseline, Week 8
Population: Participants from the Full Analysis Set (FAS), defined as all participants who were randomized and received at least 1 dose of study drug, who had data available for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vortioxetine | Change From Baseline in the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14) Total Score at Week 8 | 8.8 scores on a scale | Standard Error 0.64 |
| Escitalopram | Change From Baseline in the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14) Total Score at Week 8 | 6.6 scores on a scale | Standard Error 0.64 |
p-value: 0.01395% CI: [0.48, 4.02]Mixed Model Repeated Measurements
Secondary
Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed
The CSFQ-14 is a structured self reported questionnaire designed to measure illness- and medication-related changes in sexual functioning consisting of 14 items that measure sexual functioning as a total score (14 items) and on the subscales of pleasure (1 item), desire/frequency (2 items), desire/interest (3 items), arousal (3 items), and orgasm (3 items), rated on an 5 point scale from 1 to 5 with a total score range from 14 to 70. Higher scores reflect higher sexual functioning. A positive change from Baseline indicates that symptoms have improved. The primary analysis was based on a mixed model for repeated measurements (MMRM) analysis of covariance with treatment, center, week, treatment-by-week interaction as fixed effects, Baseline CSFQ-14 total score-by-week as covariate, and a completely unstructured covariance matrix.
Time frame: Baseline and Weeks 1, 2, 4 and 6
Population: Participants from the FAS, defined as all participants who were randomized and received at least 1 dose of study drug, who had data available for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Vortioxetine | Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed | Week 1 (n=213, 206) | 2.5 scores on a scale | Standard Error 0.39 |
| Vortioxetine | Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed | Week 2 (n=203, 200) | 4.9 scores on a scale | Standard Error 0.46 |
| Vortioxetine | Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed | Week 4 (n=187, 188) | 7.0 scores on a scale | Standard Error 0.55 |
| Vortioxetine | Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed | Week 6 (n=175, 176) | 8.0 scores on a scale | Standard Error 0.59 |
| Escitalopram | Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed | Week 6 (n=175, 176) | 6.4 scores on a scale | Standard Error 0.6 |
| Escitalopram | Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed | Week 1 (n=213, 206) | 2.2 scores on a scale | Standard Error 0.4 |
| Escitalopram | Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed | Week 4 (n=187, 188) | 4.8 scores on a scale | Standard Error 0.55 |
| Escitalopram | Change From Baseline in the CSFQ-14 Total Score at All Other Time Points Assessed | Week 2 (n=203, 200) | 3.7 scores on a scale | Standard Error 0.47 |
Secondary
Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed
The CSFQ-14 is a structured self reported questionnaire designed to measure illness- and medication-related changes in sexual functioning consisting of 14 items that measure sexual functioning as a total score (14 items) and on the subscales of pleasure (1 item), desire/frequency (2 items), desire/interest (3 items), arousal (3 items), and orgasm (3 items), rated on an 5 point scale from 1 to 5 with a total score range from 14 to 70. Higher scores reflect higher sexual functioning. Normal sexual functioning is defined as a CSFQ-14 total score of \>41 for women and \>47 for men. Abnormal sexual functioning is defined as a CSFQ-14 total score of ≤41 for women and ≤47 for men. All subjects entered the study with abnormal sexual functioning. A shift to normal indicates that symptoms have improved.
Time frame: Baseline and Weeks 1, 2, 4, 6 and 8
Population: Participants from the FAS, defined as all participants who were randomized and received at least 1 dose of study drug, who had data available for this outcome measure. Last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vortioxetine | Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Week 2 (n=217, 206) | 81 number of participants |
| Vortioxetine | Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Week 6 (n=217, 206) | 112 number of participants |
| Vortioxetine | Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Week 4 (n=217, 206) | 93 number of participants |
| Vortioxetine | Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Week 8 (n=217, 206) | 113 number of participants |
| Vortioxetine | Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Week 1 (n=213, 205) | 48 number of participants |
| Escitalopram | Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Week 8 (n=217, 206) | 91 number of participants |
| Escitalopram | Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Week 1 (n=213, 205) | 36 number of participants |
| Escitalopram | Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Week 2 (n=217, 206) | 63 number of participants |
| Escitalopram | Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Week 4 (n=217, 206) | 84 number of participants |
| Escitalopram | Number of Participants With Shifts in the CSFQ-14 From Abnormal to Normal at Each Week Assessed | Week 6 (n=217, 206) | 93 number of participants |