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Vortioxetine for Posttraumatic Stress Disorder

Evaluation of the Efficacy of Vortioxetine for Posttraumatic Stress Disorder

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02637895
Enrollment
41
Registered
2015-12-22
Start date
2016-12-31
Completion date
2020-02-06
Last updated
2021-02-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Post-Traumatic Stress Disorder

Keywords

PTSD,, trauma, stress disorder, post-traumatic stress disorder, anxiety disorder

Brief summary

Post-traumatic stress disorder (PTSD) can result from having experienced or witnessed a traumatic event. Patients with PTSD symptoms can sometimes experience symptom relief after treatment with antidepressants; however, few patients experience complete symptom relief. There is a need to develop new treatments for PTSD. This study will evaluate if 12 weeks of using Vortioxetine relieves PTSD symptoms. Vortioxetine has been approved for the treatment of depression; however, Vortioxetine has not been approved by the Food and Drug Administration for the treatment of PTSD.

Detailed description

Patients included in the study will either take the study medication or will take a placebo, a pill without the active medication. This will be determined by chance like a flip of a coin. Study procedures will include taking study medication and coming to regular in-clinic visits. Depending on the study visit, study tests may include the following: medical evaluations, physical exams, body measurements, vital signs, blood and urine tests, pregnancy tests, genetic testing, heart function monitoring, clinical and psychiatric measures, neuropsychological testing (for example, investigators will test how well you remember words or how fast you perform a certain task), a function test (for example, investigators will test how well you perform certain daily tasks), and a test to measure your startle response. A startle response is an unexpected response by a sudden activity.

Interventions

DRUGPlacebo

Placebo pill matching Vortioxetine.

DRUGVortioxetine

Immediate Release 10 mg. Vortioxetine Pill

Sponsors

Takeda
CollaboratorINDUSTRY
Emory University
CollaboratorOTHER
University of Miami
Lead SponsorOTHER

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 65 Years
Healthy volunteers
No

Inclusion criteria

Inclusion 1. Males and Females between the ages of 18 and 65 2. Fulfills Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for primary diagnosis of PTSD. 3. Able to give consent 4. Willingness to sign the treatment contract 5. A negative urine toxicology 6. For females of reproductive age, use of an effective birth control method\* for the duration of the study or abstinence. 7. Duration of illness of PTSD for at least 3 months 8. An initial score at Screening, and Visit 3 (randomization) of ≥ 50 on the Clinician Administered PTSD Scale (CAPS) for PTSD Studies Exclusion 1. Lifetime or current diagnosis of schizophrenia or other psychotic disorder, dementia, bipolar disorder. 2. Subject is currently participating in another clinical trial in which s/he is or will be exposed to an investigational or non-investigational drug or device, or has done so within the preceding month. 3. Current evidence or history of significant unstable medical illness or organic brain impairment, including stroke, Central Nervous System (CNS) tumor, demyelinating disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment that would likely interfere with the action, absorption, distribution, metabolism, or excretion of Vortioxetine. History of moderate or more severe Traumatic Brain Injury (TBI) will also be exclusionary. 4. Patients who in the investigator's judgment pose a current suicidal or homicidal risk 5. DSM-5 substance abuse or dependence within the past 90 days. Subject has a positive urine toxicology test for illegal substances. 6. Diagnosis of anorexia nervosa, bulimia, or Obsessive Compulsive Disorder (OCD) in the past year. 7. Subject has a documented history of hepato-biliary disease including a history of, or positive laboratory results for hepatitis (hepatitis B surface antigen and/or hepatitis C antibody), and clinically significant hepatic enzyme elevation, including any one of the following enzymes greater than 3 times the upper limit of normal (ULN) value (Alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase( ALP)), or total or direct bilirubin \> 1.5 x ULN, unless consistent with presumed or diagnosed Gilbert's disease 8. Subject has taken systemic corticosteroids within 2 weeks of the Randomization Visit 9. Treatment with any other psychoactive medication within 2 weeks of Visit 1, including all antidepressants, psychoactive herbal or nutritional treatment (St Johns Wort,S-Adenosyl methionine(SAM-e)), lithium, other mood stabilizers, oral antipsychotics, depot antipsychotics within 12 weeks, beta blockers, thioridazine, pimozide, opiates, anxiolytics, and sedatives (with the exception of zolpidem, eszopiclone, and zaleplon). Also any treatment with any medication that the PI judges not acceptable for this study. 10. Pregnancy or lactation\* 11. Subjects who, in the opinion of the investigator, would be noncompliant with the visit schedule or study procedures (e.g. illiteracy, planned vacations, or planned hospitalizations during the study). 12. Any laboratory abnormality that in the investigator's judgment is considered to be clinically significant 13. Patients who are receiving exposure-based psychotherapy that targets PTSD symptoms 14. Current or planned litigation or other actions related to secondary gain regarding the traumatic event 15. Subject has clinical evidence of, or ElectroCardiogram (ECG) results indicating any of the following at either screen or Randomization Visit unless repeat ECG shows that the parameter had returned to within normal range by the Randomization Visit: * Q to T interval change (QTc)\> 450 msec for men, or \> 475 msec for women; * any cardiac condition or ECG evidence that the investigator feels may pose a potential safety concern.

Design outcomes

Primary

MeasureTime frameDescription
Change Clinician Administered PTSD Scale ScoreBaseline, Up to Week 12Clinician-Administered PTSD Scale (CAPS-5) has a total score ranging from 0-80 with the higher score indicating greater degree of PTSD symptom severity.

Secondary

MeasureTime frameDescription
Number of Participants That Achieve Treatment Response Via Clinician Administered PTSD Scale (CAPS)-5Week 12Number of participants that achieve treatment response will be reported as those that has achieved a 30% improvement in their CAPS-5 total score from baseline. CAPS-5 has a total score ranging from 0-80 with the higher score indicating greater degree of PTSD symptom severity. Observed cases only.
Change in Depressive Symptoms in PTSDBaseline, Up to Week 12Montgomery-Asberg Depression Rating Scale (MADRS) has a total score ranging from 0-60, with 0 meaning no depressive symptoms and 60 meaning severe depressive symptoms.(MADRS). From the total score 0-60, with 0 meaning no depressive symptoms and 60 meaning severe depressive symptoms.
Number of Participants That Achieve Treatment Response Via CGI-IWeek 12Clinical Global Impression of Improvement (CGI-I) is a 7 point Likert-scale questionnaire assessing PTSD symptoms improvement. A score of 1 indicates very much improved, 4 indicates no change and 7 indicates much worse. Treatment response will be reported as the number of participants with an improvement of 1-2 points on their CGI-I score from baseline. Analysis includes observed cases only.

Countries

United States

Participant flow

Participants by arm

ArmCount
Placebo
Placebo pill once daily for 12 weeks of active treatment. Placebo: Placebo pill matching Vortioxetine.
21
Vortioxetine
Vortioxetine pill 10mg once daily up to 4 weeks followed by 20mg once daily if tolerated for the rest of the study. Patients unable to tolerate the 20 mg/day dose may be reduced to 10 mg/day between weeks 4 and 8. The dose of study medication should remain stable for weeks 8-12. Vortioxetine: Vortioxetine pill 10mg once daily up to 4 weeks followed by 20mg once daily if tolerated for the rest of the study. Patients unable to tolerate the 20 mg/day dose may be reduced to 10 mg/day between weeks 4 and 8. The dose of study medication should remain stable for weeks 8-12.
20
Total41

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAbnormal baseline lab01
Overall StudyLack of Efficacy10
Overall StudyLost to Follow-up40
Overall StudyProtocol Violation01
Overall StudyWithdrawal by Subject11

Baseline characteristics

CharacteristicVortioxetineTotalPlacebo
Age, Continuous44.3 years
STANDARD_DEVIATION 11.9
42.2 years
STANDARD_DEVIATION 11.4
40.1 years
STANDARD_DEVIATION 11
Ethnicity (NIH/OMB)
Hispanic or Latino
4 Participants9 Participants5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
16 Participants32 Participants16 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
2 Participants4 Participants2 Participants
Race (NIH/OMB)
Black or African American
9 Participants18 Participants9 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
9 Participants19 Participants10 Participants
Sex: Female, Male
Female
14 Participants28 Participants14 Participants
Sex: Female, Male
Male
6 Participants13 Participants7 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 210 / 20
other
Total, other adverse events
11 / 2115 / 20
serious
Total, serious adverse events
0 / 210 / 20

Outcome results

Primary

Change Clinician Administered PTSD Scale Score

Clinician-Administered PTSD Scale (CAPS-5) has a total score ranging from 0-80 with the higher score indicating greater degree of PTSD symptom severity.

Time frame: Baseline, Up to Week 12

Population: Mixed Model Repeated Measures (MMRM) Analysis of all Intent To Treat (ITT) cases

ArmMeasureValue (MEAN)Dispersion
PlaceboChange Clinician Administered PTSD Scale Score16 score on a scaleStandard Error 3
VortioxetineChange Clinician Administered PTSD Scale Score17 score on a scaleStandard Error 2.7
Secondary

Change in Depressive Symptoms in PTSD

Montgomery-Asberg Depression Rating Scale (MADRS) has a total score ranging from 0-60, with 0 meaning no depressive symptoms and 60 meaning severe depressive symptoms.(MADRS). From the total score 0-60, with 0 meaning no depressive symptoms and 60 meaning severe depressive symptoms.

Time frame: Baseline, Up to Week 12

Population: Mixed Model Repeated Measures (MMRM) Analysis of all Intent To Treat (ITT) cases

ArmMeasureValue (MEAN)Dispersion
PlaceboChange in Depressive Symptoms in PTSD9.73 score on a scaleStandard Error 1.95
VortioxetineChange in Depressive Symptoms in PTSD12.06 score on a scaleStandard Error 2.27
Secondary

Number of Participants That Achieve Treatment Response Via CGI-I

Clinical Global Impression of Improvement (CGI-I) is a 7 point Likert-scale questionnaire assessing PTSD symptoms improvement. A score of 1 indicates very much improved, 4 indicates no change and 7 indicates much worse. Treatment response will be reported as the number of participants with an improvement of 1-2 points on their CGI-I score from baseline. Analysis includes observed cases only.

Time frame: Week 12

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
PlaceboNumber of Participants That Achieve Treatment Response Via CGI-I10 Participants
VortioxetineNumber of Participants That Achieve Treatment Response Via CGI-I11 Participants
Secondary

Number of Participants That Achieve Treatment Response Via Clinician Administered PTSD Scale (CAPS)-5

Number of participants that achieve treatment response will be reported as those that has achieved a 30% improvement in their CAPS-5 total score from baseline. CAPS-5 has a total score ranging from 0-80 with the higher score indicating greater degree of PTSD symptom severity. Observed cases only.

Time frame: Week 12

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
PlaceboNumber of Participants That Achieve Treatment Response Via Clinician Administered PTSD Scale (CAPS)-59 Participants
VortioxetineNumber of Participants That Achieve Treatment Response Via Clinician Administered PTSD Scale (CAPS)-511 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026