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

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.

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.