| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| post traumatic stress disorder |
|
| E.1.1.1 | Medical condition in easily understood language |
| post traumatic stress disorder |
|
| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The co-primary objectives are to determine whether JNJ-42165279 will:
1. In combination with an 8-week internet-delivered cognitive behavioral therapy (iCBT), reduce PTSD symptom severity as measured using change from baseline in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5).
2. After 4 weeks, result in potentiated extinction of conditioned fear responses using a laboratory fear condition paradigm.
|
|
| E.2.2 | Secondary objectives of the trial |
To evaluate whether JNJ-42165279 will:
1. Together with iCBT, reduce severity of self-reported anxiety and depression symptoms.
2. Attenuate negative affect produced by exposure to a laboratory stressor as assessed by facial electromyography (EMG). In addition, we will evaluate self-report, psychophysiological, and plasma biomarkers of stress responses.
3. Influence the neural circuitry underlying emotion regulation. Specifically, enhance connectivity between the amygdala and vmPFC.
4. Influence sleep as assessed via self-report and continuous physiological monitoring
5. Result in a reduction of PTSD symptom severity that persists for appr. 1 month after medication has been discontinued
6. Result in a reduction of PTSD symptom severity that precedes initiation of internet-based CBT
7. Improve recollection of therapy content
8. Evaluate the use of latent technology in continuous patient monitoring and describe patient characteristics on behaviours associated with PTSD symptoms
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Age >18 and <65 years.
2. Diagnosed with current PTSD according to the Diagnostic and Statistical Manual of Mental Disorders-5 DSM-5, as determined by The Mini International Neuropsychiatric Interview, MINI-7.0 for DSM-5 and clinical examination.
3. Has a PCL-5 score ≥32
4. Reports PTSD-related symptoms as chief medical complaint
5. Willing to provide informed consent and comply with study procedures.
6. Able to self-administer study medication and swallow it whole with water
7. Able to speak and read Swedish.
8. Has access to computer, tablet or other device enabling interaction with internet-based intervention.
9. To be eligible, women must have a negative serum or urine pregnancy test prior to the start of study drug, and either not be of childbearing potential, or agree to use a method of contraception that is highly effective for the duration of the study and for 4 weeks after receiving the last dose of study medication. Not of childbearing potential is defined as postmenopausal (>45 years of age with amenorrhea for at least 12 months, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level >40 IU/L); permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy); not heterosexually active in the past 12 years and not having an intent of becoming heterosexually active in the coming 12 months; or otherwise incapable of pregnancy.
10. Subjects must be otherwise healthy for their age group or medically stable with or without medication, as determined by physical examination, medical history, vital signs, and 12-lead ECG performed at the eligibility assessment visit or at the baseline visit. If there are abnormalities, they must be consistent with any known, underlying condition of the participant that is stable under treatment; or they must be without clinical significance. This determination will be made by the Investigator or designee, aided by specialist consults as needed, and documented.
11. Subjects must be otherwise healthy or medically stable on the basis of clinical laboratory tests performed at the eligibility assessment visit. If the results are outside the normal reference ranges, the subject may be included only if the abnormalities or deviations from normal are deemed not to be clinically significant. This determination will be made by the Investigator or designee, aided by specialist consults as needed, and documented.
|
|
| E.4 | Principal exclusion criteria |
1. A lifetime history of any major psychiatric disorder that limits or may come to limit the ability of the subject to provide informed consent, comply with study procedures, or safely participate in the study; including, but not limited to schizophrenia or other chronic psychotic disorder, or bipolar disorder.
2. A current psychiatric condition that may limit the ability of the subject to comply with study procedures or put subject at unacceptable risk; including but not limited to psychotic depression, severe eating disorder, borderline personality disorder or severe obsessive-compulsive disorder.
3. A current cognitive impairment that could interfere with the ability of a subject to provide informed consent or comply with study procedures.
4. A current clinical diagnosis of severe alcohol use disorder or current clinically significant alcohol withdrawal syndrome.
5. A current clinical diagnosis of moderate or severe substance use disorder, other than nicotine
6. Any presence of an illicit substance on eligibility assessment visit urine toxicology screen
7. A current or recent history of clinically significant suicidal ideation, or a history of suicidal behavior within the past year. Subjects with a prior suicide attempt, or prior serious suicidal ideation/plan > 6 months ago will be carefully screened for current suicidal ideation and only included at the discretion of the Investigator.
8. Insufficient memory of the trauma (for prolonged exposure to be effective).
9. Ongoing traumatization
10. A dissociative disorder which is more severe or affects the subject more than their PTSD.
11. Any ongoing specific psychological treatment for PTSD.
12. Use of any psychotropic medications within the past 14 days (4 weeks for fluoxetine), unless the dose has been stable for the past 4 weeks and will be kept unchanged throughout the course of the study.
13. Daily (but not sporadic) use of a benzodiazepine or related sedative / anxiolytic medication.
14. Use of moderate or strong inhibitors and inducers of CYP3A4.
15. Current or past thyroid disease or dysfunction that is not currently stable in treatment or monitored.
16. Any abnormal finding on a 12-lead ECG, unless not clinically significant.
17. A history of or current liver or renal insufficiency; clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, rheumatologic, psychiatric, or metabolic disturbances (e.g. unstable situation needing monitoring or regular dose adaptations).
18. A history of malignancy within 5 years before eligibility assessment (with the exception of squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the judgment of the Investigator, aided by specialist consults as needed, is considered cured with minimal risk of recurrence).
19. A history of positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at eligibility assessment; unless successfully treated as shown by RNA / DNA tests, or due to previous vaccine exposure.
20. A history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at eligibility assessment.
21. Major surgery, (e.g. requiring general anesthesia) within 8 weeks before eligibility assessment, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 4 weeks after the last dose of study drug administration. Subjects with planned surgical procedures to be conducted under local anesthesia may participate.
22. History of spontaneous, prolonged or severe bleeding, or has donated one or more units (approximately 450 mL) of blood or had acute loss of an equivalent amount of blood within 90 days prior to study drug administration.
23. Any other medical condition due to which participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments.
24. Pregnancy, breast-feeding, or planning to become pregnant.
25. People with counter-indications to MRI scanning or task completion who are otherwise eligible and provide consent will be excluded from the MRI session, but will otherwise be able to participate.
26. Subject has received an investigational drug or used an investigational medical device within 3 months before the planned start of study or is currently enrolled in an investigational study.
27. Subject is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site; or is a family member of the employees or the investigator.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
* PTSD symptoms measured as DSM-5 (CAPS-5)
* extinction of conditioned fear responses
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
* PTSD symptoms: 12 weeks after baseline
* exctionction of conditioned fear responses: 4 weeks after baseline |
|
| E.5.2 | Secondary end point(s) |
* self-reported anxiety and depression symptoms
* self-reported, psychophysiological, and plasma biomarkers of stress responses
* connectivity between the amygdala and vmPFC evaluated by MRI
* sleep as assessed via self-report and continuous physiological monitoring
* PTSD symptom severity
* Patient characteristics as determined by the analysis of multiple streams of physiological, actigraphy and electronically-captured patient reportred (ePRO) data on behaviours associated with PTSD symptoms |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
