A Pilot Dose-Response Biomarker Study of Brexpiprazole Treatment in PTSD

NCT02934932 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: Pro00071923
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Determine if brexpiprazole treatment will be associated with a dose-dependent reduction in resting pupil diameter as a reflection of locus coeruleus (LC) norepinephrine (NE) neuron target engagement in a group of subjects with PTSD. All subjects will be evaluated by physical examination, ECG, standard blood chemistry, hematologic labs, toxicology testing, and urinalysis. Results of these studies must demonstrate a lack of clinically significant abnormalities prior to enrollment. Subjects will need to satisfy DSM-5 criteria for PTSD and receive a CAPS-5 score of 40 or greater on testing for study enrollment. Resting pupil diameter during pupillometric evaluation after two weeks on each treatment will serve as the primary outcome measure. This will be compared in the treatment groups using mixed effects repeated measures models to evaluate if there is a significant difference in pupil size among the treatments studied. As a secondary analysis this approach will be used to evaluate whether there is treatment effect on total CAPS-5 score. Lastly, the investigators will compute correlations between pupil size and CAPS-5 scores.

Conditions

Post Traumatic Stress Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Resting Pupil Diameter

  Evaluate the effects of two doses of brexpiprazole on locus coeruleus (LC) norepinephrine (NE) neuron activity.

  Baseline to 6 weeks for each treatment arm

Secondary Outcomes (1)

• Change in CAPS-5 Ratings Score

  Baseline to 6 weeks for each treatment arm

Study Arms (3)

Brexpiprazole 2mg

EXPERIMENTAL

Subjects will be titrated to this dose of brexpiprazole for 6 weeks.

Drug: Brexpiprazole

Brexpiprazole 4mg

EXPERIMENTAL

Subjects will be titrated to this dose of brexpiprazole for 6 weeks.

Drug: Brexpiprazole

Placebo

PLACEBO COMPARATOR

Subjects will be titrated to this dose of placebo for 6 weeks.

Drug: Brexpiprazole

Interventions

Brexpiprazole DRUG

Comparison of brexpiprazole 2mg to placebo Comparison of brexpiprazole 4mg to placebo

Also known as: Rexulti

Brexpiprazole 2mg; Brexpiprazole 4mg; Placebo

Eligibility Criteria

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

You may qualify if:

• Participants will be 18-65 years of age.
• All subjects will be evaluated by physical examination, ECG, standard blood chemistry, hematologic labs, toxicology testing, and urinalysis at baseline and end of study. Results of these studies must demonstrate a lack of clinically significant abnormalities prior to enrollment. If results are outside of the normal reference range the study physician will be consulted to assess if clinically significant.
• Subjects will need to satisfy DSM-5 criteria for PTSD and receive a CAPS-5 score of 40 or greater on testing for study enrollment.
• Subjects will need to be free of psychotropic medications or treatments that could impact results of this study as deemed by the PI for at least 1 week.
• If the subject's primary psychiatrist or treating primary care physician are providing the subject with psychotropic medications they will be notified and a discussion about tapering current psychotropic medications prior to study enrollment will occur.

You may not qualify if:

• Subjects will be excluded if they have significant medical or neurologic conditions (other than mild to moderate TBI), specifically seizures, or movement disorders,
• have substance abuse within 12 months of study enrollment, substance dependence within past three months, per DSM-5 criteria (excluding caffeine and nicotine). The absence of substance use will be determined by self-report and confirmed by the results of urine toxicology at screening.
• Women who are pregnant, breast-feeding, or planning to become pregnant while enrolled in this study will also be excluded.
• Subjects with a history of severe drug allergy or hypersensitivity, or known hypersensitivity to the Brexpiprazole or its ingredients.
• The subject has a history of tardive dyskinesia.
• The subject has clinically significant extrapyramidal symptoms (EPS) including akathisia.
• The subject has epilepsy or a history of seizures, except for a single seizure episode (e.g., childhood febrile seizure, post traumatic, or alcohol withdrawal).
• The subject has chronic, uncontrolled, or unstable clinically relevant medical conditions Including:
• Uncontrolled hypertension defined as blood pressure greater than 180/90
• Hypotension defined as a blood pressure less than 90/60
• Moderate to severe hepatic impairment (Child-Pugh score ≥7)
• Moderate, Severe or End-Stage Renal Impairment (CrCL \<60ml/min)
• Known CYP2DG Poor Metabolizers
• Heart failure NYHA Class III or IV
• Diabetes mellitus or HbA1c greater than 5.7% (which defines pre-diabetes)

Sponsors & Collaborators

• Duke University: lead
• Otsuka America Pharmaceutical: collaborator

Study Sites (1)

Pamela Smith

Durham, North Carolina, 27712, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

brexpiprazole

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Steven Szabo
• Organization: Duke University

steven.szabo@duke.edu

919-681-8742

Study Officials

• Steven T Szabo, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2016
• First Posted: October 17, 2016
• Study Start: April 25, 2017
• Primary Completion: April 30, 2018
• Study Completion: April 30, 2018
• Last Updated: March 5, 2019
• Results First Posted: March 5, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)