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

• Sponsor: Lori Davis, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01587118
• Collaborator: Merck Sharp & Dohme LLC (Industry), Forest Laboratories (Industry)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 49
• Patients Per Site Per Month: 0.4

Study Details

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
• 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: Jun 1, 2012
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 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 [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) [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

Criteria

• Ages Eligible for Study: 19 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Tuscaloosa VA Medical Center	Tuscaloosa	Alabama	United States	35404

Sponsors and Collaborators

• Lori Davis, MD
• Merck Sharp & Dohme LLC
• Forest Laboratories

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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: Apr 27, 2012
• Last Update Posted: Jun 11, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Lori Davis, MD, Associate Chief of Staff, Research and Development Service, 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; Asenapine

Study Results

Participant Flow

Arm/Group Title	Antidepressant Plus Asenapine
Arm/Group Description	adjunctive asenapine 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.
Period Title: Overall Study
STARTED	18
COMPLETED	11
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Antidepressant Plus Asenapine
Arm/Group Description	adjunctive asenapine 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.
Overall Participants	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.3 (11.9)
Sex: Female, Male (Count of Participants)
Female	3 16.7%
Male	15 83.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	11 61.1%
White	6 33.3%
More than one race	1 5.6%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Clinical Administered PTSD Scale (CAPS) Total
Description	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.
Time Frame	baseline, week 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Open label treatment, all participants included.Overall change in values from baseline to week 12, including weeks 4 and 8, using a simple one-way analysis of variance; because the sample size was small, p-values for the paired t-test and one-way results were recalculated using the signed rank test and Kruskal Wallis procedure, respectively

Arm/Group Title	Antidepressant Plus Asenapine
Arm/Group Description	adjunctive asenapine 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.
Measure Participants	18
Mean (Standard Deviation) [units on a scale]	-39 (18.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Antidepressant Plus Asenapine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments	The a priori threshold for statistical significance was p</= 0.05
	Method	ANOVA
	Comments	Change from baseline analyses were conducted using simple one-way analysis of variance; and were recalculated using the Kruskal Wallis procedure.

2. Secondary Outcome

Title	Change From Baseline in Brief Psychiatric Rating Scale (BPRS)
Description	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.
Time Frame	Baseline, week 4, 8, 12

Outcome Measure Data

Analysis Population Description

Open label treatment, all participants included.Overall change in values from baseline to week 12, including weeks 4 and 8, using a simple one-way analysis of variance; because the sample size was small, p-values for the paired t-test and one-way results were recalculated using the signed rank test and Kruskal Wallis procedure, respectively

Arm/Group Title	Antidepressant Plus Asenapine
Arm/Group Description	adjunctive asenapine 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.
Measure Participants	18
Mean (Standard Deviation) [units on a scale]	-15.5 (9.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Antidepressant Plus Asenapine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.0006
	Comments	The a priori threshold for statistical significance was p</= 0.05
	Method	ANOVA
	Comments	Change from baseline analyses were conducted using simple one-way analysis of variance; and were recalculated using the Kruskal Wallis procedure.

Adverse Events

Time Frame	Adverse events were collected for the 12 weeks of active study participation; Serious adverse events were collected for the 12 weeks of study and one additional post-study month.
Arm/Group Title	Antidepressant Plus Asenapine
Arm/Group Description	adjunctive asenapine 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.
All Cause Mortality
	Antidepressant Plus Asenapine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Antidepressant Plus Asenapine
	Affected / at Risk (%)	# Events
Total	1/18 (5.6%)
Psychiatric disorders
Psychiatric hospitalization	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Antidepressant Plus Asenapine
	Affected / at Risk (%)	# Events
Total	6/18 (33.3%)
Gastrointestinal disorders
upset stomach	1/18 (5.6%)	1
General disorders
fatigue	1/18 (5.6%)	1
agitation	1/18 (5.6%)	1
Infections and infestations
sinus infection	1/18 (5.6%)	1
Metabolism and nutrition disorders
weight gain	1/18 (5.6%)	1
Nervous system disorders
sedation with syncope	1/18 (5.6%)	1
sedation	2/18 (11.1%)	2
extrapyramidal side effect	1/18 (5.6%)	1
Headache	1/18 (5.6%)	1

Limitations/Caveats

This study was limited by both the small number of subjects enrolled and its open-label design. Average dose of asenapine was 13.6 ± 6.4 mg/d; at 12-weeks 15.9 ± 4.9 mg/d.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.