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

• Status: Terminated
• Trial end date: 2018-04-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborator: Otsuka America Pharmaceutical
• Treatments: Brexpiprazole

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

1. Subjects will be excluded if they have significant medical or neurologic conditions (other than mild to moderate TBI), specifically seizures, or movement disorders,

2. 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.

3. Women who are pregnant, breast-feeding, or planning to become pregnant while enrolled in this study will also be excluded.

4. Subjects with a history of severe drug allergy or hypersensitivity, or known hypersensitivity to the Brexpiprazole or its ingredients.

5. The subject has a history of tardive dyskinesia.

6. The subject has clinically significant extrapyramidal symptoms (EPS) including akathisia.

7. 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).

8. 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)

• Hypertriglyceridemia defined as triglycerides greater than 200mg/dL

• Low white blood cell count (below lower range of normal)

• History of leukopenia or neutropenia

• Arrhythmia with heart rate greater than 100bpm

• Myocardial infarction in the past 6 months

• Cerebrovascular accident in the past 6 months

• Recurrent syncope

• Seizure disorder

• Currently receiving treatment for malignancy

• QTc interval of greater than 450ms on electrocardiogram

9. The subject has a neurodegenerative disorder (Alzheimer disease, Parkinson's disease, multiple sclerosis, Huntington disease, etc.).