Effect of Lu AA21004 Versus Escitalopram on Sexual Functioning in Adults With Well-Treated Major Depressive Disorder

• Change from Baseline in the CSFQ-14 total score (Week 1). [ Time Frame: Baseline and Week 1. ] [ Designated as safety issue: No ]
  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. Lower scores are associated with worsened sexual functioning.
• Change from Baseline in the CSFQ-14 total score (Week 2). [ Time Frame: Baseline and Week 2. ] [ Designated as safety issue: No ]
  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. Lower scores are associated with worsened sexual functioning.
• Change from Baseline in the CSFQ-14 total score (Week 4). [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
  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. Lower scores are associated with worsened sexual functioning.
• Change from Baseline in the CSFQ-14 total score (Week 6). [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
  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. Lower scores are associated with worsened sexual functioning.
• Number of participants with a shift in the CSFQ-14 from abnormal (defined as a CSFQ-14 total score ≤41 for women and ≤47 for men) at Baseline, to normal (defined as >41 for women and >47 for men) (Week 1). [ Time Frame: Baseline and Week 1. ] [ Designated as safety issue: No ]
  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. Lower scores are associated with worsened sexual functioning.
• Number of participants with a shift in the CSFQ-14 from abnormal (defined as a CSFQ-14 total score ≤41 for women and ≤47 for men) at Baseline, to normal (defined as >41 for women and >47 for men) (Week 2). [ Time Frame: Baseline and Week 2. ] [ Designated as safety issue: No ]
  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. Lower scores are associated with worsened sexual functioning.
• Number of participants with a shift in the CSFQ-14 from abnormal (defined as a CSFQ-14 total score ≤41 for women and ≤47 for men) at Baseline, to normal (defi ned as >41 for women and >47 for men) (Week 4). [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
  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. Lower scores are associated with worsened sexual functioning.
• Number of participants with a shift in the CSFQ-14 from abnormal (defined as a CSFQ-14 total score ≤41 for women and ≤47 for men) at Baseline, to normal (defined as >41 for women and >47 for men) (Week 6). [ Time Frame: Baseline and Week 6. ] [ Designated as safety issue: No ]
  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. Lower scores are associated with worsened sexual functioning.
• Number of participants with a shift in the CSFQ-14 from abnormal (defined as a CSFQ-14 total score ≤41 for women and ≤47 for men) at Baseline, to normal (defined as >4 for women and >47 for men) (Week 8). [ Time Frame: Baseline and Week 8. ] [ Designated as safety issue: No ]
  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. Lower scores are associated with worsened sexual functioning.

The purpose of this study is to evaluate the effects of Lu AA21004, once daily (QD), compared with escitalopram on sexual functioning.

Depression has been recognized as a chronic illness that imposes a significant burden on individuals, families and society. Major depressive disorder (MDD) is among the most important causes of disability worldwide, in both developing and developed countries.

Lu AA21004 is under codevelopment by Takeda Global Research & Development Center, Inc. and H. Lundbeck A/S for the treatment of MDD and general anxiety disorder (GAD).

Treatment with antidepressants, including selective serotonin reuptake inhibitors (SSRIs), may be associated with sexual dysfunction, which can result in poor treatment compliance or antidepressant treatment discontinuation.

The objective of this study is to further investigate effects of Lu AA21004 in sexual functioning compared with an SSRI, escitalopram, over 8 weeks of treatment by using an objective measure, the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14), in adult participants with well treated MDD but are experiencing SSRI-induced sexual dysfunction.

Participants will be seen weekly during the first 2 weeks of treatment and then every 2 weeks up to the end of the 8-week Treatment Period.

Participants who complete the 8-week Treatment Period will enter a 1-week, double-blind, Taper-Down Period.

• Drug: Lu AA21004

  Lu AA21004 10 mg, capsules, orally, once daily for 1 week, then dose adjustment to a maximum 20 mg, capsules, orally, once daily for up to 7 weeks.

  At week 8, Lu AA21004 placebo-matching capsules, orally, once daily for 1 week only.

• Drug: Escitalopram

  Escitalopram 10 mg, capsules, 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.

  Other Name: Lexapro

• Experimental: Lu AA21004 QD
  Intervention: Drug: Lu AA21004
• Active Comparator: Escitalopram QD
  Intervention: Drug: Escitalopram

Inclusion Criteria:

1. Participant is a man or a woman aged between 18 and 55 years, inclusive, who is currently being treated with 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. The depression is currently stable; and the subject has a Clinical Global Impression Scale-Severity of Illness Scale (CGI-S) score of ≤3.
3. The participant is currently experiencing treatment-emergent sexual dysfunction (TESD; defined as a 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. The participant has previously participated in a Lu AA21004 clinical study.
2. The participant 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. 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. Male participant 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. The participant or participant's sexual partner(s) plans to initiate treatment for sexual dysfunction during the study.