An Open Label Pilot Study of Adjunctive Asenapine for the Treatment of Posttraumatic Stress Disorder

• ClinicalTrials.gov Identifier: NCT01587118
• Recruitment Status: Completed
• First Posted: April 27, 2012
• Results First Posted: December 5, 2016
• Last Update Posted: June 11, 2019
• Sponsor: Lori Davis, MD
• Collaborators: Merck Sharp & Dohme Corp.; Forest Laboratories
• Information provided by (Responsible Party): Lori Davis, MD, Tuscaloosa Research & Education Advancement Corporation

Study Description

Brief Summary:

This is an open-label pilot study of adjunctive asenapine for the treatment of Posttraumatic Stress Disorder (PTSD) in veterans who have not fully remitted to an adequate trial of standard antidepressant treatment.

Condition or disease	Intervention/treatment	Phase
Posttraumatic Stress Disorder	Drug: Adjunctive asenapine	Phase 4

Detailed Description:

Consenting Veterans with the diagnosis of PTSD who have not fully remitted to an adequate trial of standard antidepressant treatment (sertraline, citalopram, escitalopram, fluoxetine, venlafaxine, or mirtazapine) are treated with the addition of open-label asenapine for 12-weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Pilot Study of Adjunctive Asenapine for the Treatment of Posttraumatic Stress Disorder
• Study Start Date: June 2012
• Actual Primary Completion Date: July 2016
• Actual Study Completion Date: July 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: antidepressant plus asenapine; adjunctive asenapine	Drug: Adjunctive asenapine; participants who are not responding fully to antidepressant therapy for PTSD will receive adjunctive asenapine (flexible dosing beginning with 5 mg sublingual once per day, titrated up to 10 mg twice per day, as tolerated) for a total of 12 weeks.; Other Names: asenapine; Saphris

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Clinical Administered PTSD Scale (CAPS) Total [ Time Frame: baseline, week 4, 8, and 12 ]
   CAPS is the clinician rating of posttraumatic stress disorder (PTSD) symptoms; higher scores indicate higher severity of PTSD; 17-item score range 0 to 136. Blake DD, Weathers FW, Nagy LM, et al. The development of a Clinician-Administered PTSD Scale. J Trauma Stress 1995; 8:75-90.

Secondary Outcome Measures :

1. Change From Baseline in Brief Psychiatric Rating Scale (BPRS) [ Time Frame: Baseline, week 4, 8, 12 ]
   BPRS is the clinician rating of psychiatric symptoms; higher score indicates higher severity; 18-items scored 1-7; highest score 126. Overall JE and Gorham DR. The Brief Psychiatric Rating Scale (BPRS): recent developments in ascertainment and scaling. Psychopharmacol Bulletin 1993; 24:97-99.

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Signed and dated informed consent and acceptable proof of identity.
• Male or female subjects ≥19 to 65 years of age of any race or ethnic origin.
• Not currently pregnant, breastfeeding or planning on becoming pregnant; use of contraception as follows:
• Males - those that are sexually active must use a double barrier method of contraception (condom with spermicide) from the first dose of asenapine until 12 weeks after last dose of asenapine
• Women of child-bearing potential - must have a negative urine pregnancy test and confirmed (by the investigator) use of a highly effective form of birth control for 3 months before enrollment and until 12 weeks after their last dose of asenapine.
• Women of non-child bearing potential - women who are either permanently sterilized (hysterectomy, bilateral oophorectomy and bilateral salpingectomy but excluding bilateral tubal occlusion) or who are postmenopausal.
• Diagnosis of PTSD (DSM-IV-TR criteria; confirmed by MINI and CAPS).
• Total CAPS score > 45.
• Currently taking an approved antidepressant at acceptable dose for 8 weeks or more with non-remission of symptoms.
• No substance use disorders of dependence (except for nicotine, caffeine) in previous 4 wks.
• No substance use disorders of abuse (except for nicotine and caffeine) in the previous 2 wks.
• Physical and laboratory panel (within past one year) are within normal limits or not clinically significant

Exclusion Criteria:

• Lifetime history of bipolar I, schizophrenia, schizoaffective or cognitive disorders (assessed by the MINI)
• Actively considering plans of suicide or homicide (assessed by clinical interview)
• Psychotic symptoms that in the investigator's opinion impair the subject's ability to give informed consent
• A contraindication to the use of asenapine or antidepessant
• Intolerable side effects or allergic reaction to asenapine or the current antidepressant
• Women planning to become pregnant or breastfeed during the study
• Clinically significant unstable or severe medical condition that would contraindicate study participation or expose them to an undue risk of a significant adverse event, including but not limited to: unstable or severe hepatic, renal, respiratory, cardiovascular, endocrine, neurologic, or hematologic disease; hypo- or hyperthyroidism, unless the condition has been stabilized; or a history of seizures (except for a single childhood febrile seizure, posttraumatic, or alcohol withdrawal). The following are exclusionary: platelets < 75,000/mm; hemoglobin <9g/dL; neutrophils, absolute < 1000/mm; LFTs > 3x upper limit; creatinine > 2 mg/dL; diastolic BP < 60 or > 110mmHg; EKG QTc > 475 msec.
• In regard to vulnerable patient populations, persons with dementia, minors (<age 19), the elderly (>age 65), prisoners and the terminally ill are excluded.

Contacts and Locations

Locations

United States, Alabama

Tuscaloosa VA Medical Center

Tuscaloosa, Alabama, United States, 35404

Sponsors and Collaborators

Lori Davis, MD

Merck Sharp & Dohme Corp.

Forest Laboratories

Investigators

• Principal Investigator: Lori L Davis, MD; Tuscaloosa Research & Education Advancement Corporation

More Information

Publications of Results:

Pilkinton P, Berry C, Norrholm S, Bartolucci A, Birur B, Davis LL. An Open Label Pilot Study of Adjunctive Asenapine for the Treatment of Posttraumatic Stress Disorder. Psychopharmacol Bull. 2016 Aug 15;46(2):8-17.

• Responsible Party: Lori Davis, MD, Associate Chief of Staff, Research and Development Service, Tuscaloosa Research & Education Advancement Corporation
• ClinicalTrials.gov Identifier: NCT01587118
• Other Study ID Numbers: 00156
• First Posted: April 27, 2012
• Results First Posted: December 5, 2016
• Last Update Posted: June 11, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No sharing of individual participant data

Keywords provided by Lori Davis, MD, Tuscaloosa Research & Education Advancement Corporation:

PTSD; Posttraumatic Stress Disorder; Asenapine; Adjunctive; antidepressant; neuroleptic

Additional relevant MeSH terms:

Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Pathologic Processes; Trauma and Stressor Related Disorders; Mental Disorders; Asenapine; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Psychotropic Drugs