Safety and Tolerability of Vortioxetine (Lu AA21004) in Adults With Major Depressive Disorder

NCT00707980 | Completed Phase 3 Results

• 3 other identifiers: LuAA21004_3012008-001581-91U1111-1113-9564
• Study Type: interventional
• Target: 836
• Locations: 17 countries
• Sites: 92

Brief Summary

The purpose of this study is to determine the long-term efficacy and safety of vortioxetine, once daily (QD), in adults with major depressive disorder.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; Depression; Melancholia; Mood Disorder; Dysthymic Disorder; Drug Therapy

Outcome Measures

Primary Outcomes (5)

• Physical Examination Findings

  Physical examination consisted of the following body systems: (1) appearance; (2) extremities; (3) skin; (4) head and neck; (5) eyes, ears, nose, and throat; (6) lungs and chest; (7) heart and cardiovascular system; (8) abdomen; and (9) musculoskeletal system. An assessment of the nervous system was conducted; any findings were captured under the appropriate body area. Each system was assessed as normal or abnormal.

  Baseline and Week 52

• Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings

  Participants with at least one post-baseline potentially clinically significant (as defined in the table below) serum chemistry, hematology or urinalysis result. ULN = upper limit of normal; LLN = Lower limit of normal.

  Weeks 4, 8, 12, 20, 28, 36, 44 and 52

• Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings

  A standard 12-lead ECG was performed at the designated study visits. The central reader reviewed and recorded the intervals (PR, QRS, RR, QT, and corrected QT interval \[QTc\]), and interpreted the ECG using 1 of the following categories: within normal limits or abnormal. The number of participants with at least one post-baseline potentially clinically significant ECG finding is reported. bpm = beats per minute; QTcB = QT interval corrected using Bazett's formula; QTcF = QT interval corrected using Fridericia's formula.

  Weeks 4, 12, 24, 36 and 52

• Number of Participants With Adverse Events (AEs)

  The intensity (severity) of each AE was defined as: * Mild: caused minimal discomfort and did not interfere in a significant manner with normal activities. * Moderate: sufficiently uncomfortable to produce some impairment of normal activities. * Severe: incapacitating, preventing the patient from participating in normal activities. The causal relationship between an AE and study drug was assessed by the investigator as Probable, Possible or Not Related; Related=AEs with causality of Possibly or Probably. A serious AE (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, led to a congenital anomaly/birth defect, or was an important medical event that either jeopardized the patient, required intervention to prevent any of the SAEs defined above, a suicide attempt or an abortion.

  From the first dose of open-label study drug until 4 weeks after the last dose (up to 56 weeks)

• Number of Participants With Potentially Clinically Significant Vital Sign Findings

  Participants with at least one potentially clinically significant post-baseline vital sign finding. The definition of clinically significant is included in the table below for each parameter. SSBP = supine systolic blood pressure; SDBP = supine diastolic blood pressure.

  Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52

Secondary Outcomes (7)

• Change From Baseline in Hamilton Depression Scale-24 Item (HAM-D24) Total Score

  Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52.

• Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score

  Baseline and Weeks 4, 24 and 52

• Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score

  Baseline and Weeks 4, 24 and 52

• Change From Baseline in the Clinical Global Impression of Severity of Illness Scale

  Baseline and Weeks 4, 24 and 52

• Change From Baseline to the Final Visit in 36-item Short-form Health Survey (SF-36)

  Baseline and Week 52

Study Arms (1)

Vortioxetine

EXPERIMENTAL

Vortioxetine 2.5 mg, 5 mg or 10 mg, encapsulated tablets, orally, once daily for up to 52 weeks. For the first week of treatment all participants received 5 mg/day vortioxetine, thereafter, the dose could be increased to 10 mg/day or decreased to 2.5 mg/day, based on participant's response and tolerability as judged by the investigator.

Drug: Vortioxetine

Interventions

Vortioxetine DRUG

Encapsulated vortioxetine immediate-release tablets

Also known as: Lu AA21004, Brintellix®

Vortioxetine

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has completed the double blind treatment period of either study Lu AA21004\_304 (NCT00672620) or LuAA21004\_305 (NCT00735709) immediately prior to enrollment in the extension study (ie, the baseline visit is the same visit as the completion visit of the double blind treatment of the preceding protocol).
• Suffers from a major depressive episode as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.xx) at entry into the prior Lu AA21004\_304 or Lu AA21004\_305 study.

You may not qualify if:

• Has Major Depressive Disorder for whom other psychiatric disorders (mania, bipolar disorder, schizophrenia, or any psychotic disorder) have been diagnosed during the prior study.
• The participant, in the investigator's opinion, has a significant risk of suicide and/or a score of ≥5 points on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale.
• The participant, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason.
• Has a clinically significant moderate or severe ongoing adverse event related to study medication from the prior study.
• Has used/uses disallowed concomitant medication.

Sponsors & Collaborators

• Takeda: lead
• H. Lundbeck A/S: collaborator

Study Sites (92)

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Beverly Hills, California, United States

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Irvine, California, United States

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Santa Ana, California, United States

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Torrance, California, United States

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Upland, California, United States

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Bradenton, Florida, United States

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Coral Springs, Florida, United States

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Fort Walton Beach, Florida, United States

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Gainesville, Florida, United States

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Jacksonville, Florida, United States

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Maitland, Florida, United States

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Orlando, Florida, United States

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South Miami, Florida, United States

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West Palm Beach, Florida, United States

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Atlanta, Georgia, United States

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Smyrna, Georgia, United States

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Chicago, Illinois, United States

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Libertyville, Illinois, United States

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Oak Brook, Illinois, United States

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Prairie Village, Kansas, United States

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Owensboro, Kentucky, United States

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Baltimore, Maryland, United States

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Pittsfield, Massachusetts, United States

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Worcester, Massachusetts, United States

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Flowood, Mississippi, United States

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New York, New York, United States

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Olean, New York, United States

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Beachwood, Ohio, United States

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Toledo, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Allenport, Pennsylvania, United States

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Lancaster, Pennsylvania, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

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Milwaukee, Wisconsin, United States

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Elizabeth Vale, Australia

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Richmond, Australia

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Southport, Australia

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Osijek, Croatia

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Zagreb, Croatia

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Bully-les-Mines, France

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Marseille, France

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Strasbourg, France

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Berlin, Germany

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Bochum, Germany

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Chemnitz, Germany

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Hüttenberg, Germany

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Leipzig, Germany

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München, Germany

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Nuremberg, Germany

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Wiesbaden, Germany

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Liepāja, Latvia

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Riga, Latvia

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Sigulda, Latvia

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Šiauliai, Lithuania

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Vilnius, Lithuania

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Kuala Lumpur, Malaysia

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SchHoogfliet, Netherlands

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Wildervank, Netherlands

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Zwijndrecht, Netherlands

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Bialystok, Poland

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Leszno, Poland

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Pruszków, Poland

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Skórzewo, Poland

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Torun, Poland

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Tuszyn, Poland

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Moscow, Russia

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Nizhny Novgorod, Russia

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Novosibirsk, Russia

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Omsk, Russia

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Saint Petersburg, Russia

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Stavropol, Russia

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Tomsk, Russia

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Belgrade, Serbia

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Bryanston, South Africa

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Durban, South Africa

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Lyttelton, South Africa

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Noordheuwel, South Africa

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Pretoria, South Africa

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Buchon, South Korea

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Gyeonggi-do, South Korea

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Incheon, South Korea

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Seoul, South Korea

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Kaohsiung City, Taiwan

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Dnipro, Ukraine

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Kiev, Ukraine

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Luhansk, Ukraine

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Simferopol, Ukraine

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Glasgow, United Kingdom

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MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Depressive Disorder; Mood Disorders; Dysthymic Disorder

Interventions

Vortioxetine

Condition Hierarchy (Ancestors)

Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• Medical Director, Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2008
• First Posted: July 2, 2008
• Study Start: June 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: August 1, 2010
• Last Updated: December 13, 2013
• Results First Posted: December 13, 2013

Record last verified: 2013-10

Locations

MY (1); PL (6); SE (1); TW (1); US (38); GB (1); KR (4); FR (3); LA (3); UA (4); AU (3); RU (7); DE (8); ZA (5); LI (2); CR (2); NL (3)