Trial Outcomes & Findings for Rivastigmine Patch in Veterans With Cognitive Impairment Following TBI (NCT NCT01670526)

Last Updated: 2018-02-27

Results Overview

The primary efficacy measure was the Hopkins Verbal Learning Test - Revised (HVLT-R) Total Recall Index. HVLT-R was administered at screen, baseline, weeks 4, and 12. The HVLT is a measure that assesses verbal learning and memory. Alternate versions of the HVLT-R were administered at each of the different time points. The test consists of 12 words which are read to participants for three consecutive trials, each trial followed by free recall. The Total Recall score is the total number of words recalled over the three trials. The primary endpoint evaluation was to compare the proportion of patients who demonstrated improvement from baseline on the HVLT-R Total Recall of at least 5-word and at week 12 between the treatment and placebo group.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

94 participants

Primary outcome timeframe

week 12

Results posted on

2018-02-27

Participant Flow

Participant milestones

Participant milestones
Measure	Rivastigmine Rivastigmine transdermal patch Rivastigmine Transdermal Patch: Cholinesterase Inhibitor	Placebo Placebo Rivastigmine Transdermal Patch: Cholinesterase Inhibitor
Overall Study STARTED	49	45
Overall Study COMPLETED	37	39
Overall Study NOT COMPLETED	12	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Rivastigmine Rivastigmine transdermal patch Rivastigmine Transdermal Patch: Cholinesterase Inhibitor	Placebo Placebo Rivastigmine Transdermal Patch: Cholinesterase Inhibitor
Overall Study Withdrawal by Subject	3	1
Overall Study Lost to Follow-up	9	5

Baseline Characteristics

Rivastigmine Patch in Veterans With Cognitive Impairment Following TBI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rivastigmine n=49 Participants Rivastigmine transdermal patch Rivastigmine Transdermal Patch: Cholinesterase Inhibitor	Placebo n=45 Participants Placebo Rivastigmine Transdermal Patch: Cholinesterase Inhibitor	Total n=94 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	49 Participants n=5 Participants	45 Participants n=7 Participants	94 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	43 Participants n=7 Participants	90 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	34 Participants n=7 Participants	64 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	49 participants n=5 Participants	45 participants n=7 Participants	94 participants n=5 Participants

PRIMARY outcome

Timeframe: week 12

Outcome measures

Outcome measures
Measure	Rivastigmine n=49 Participants Rivastigmine transdermal patch Rivastigmine Transdermal Patch: Cholinesterase Inhibitor	Placebo n=45 Participants Placebo Rivastigmine Transdermal Patch: Cholinesterase Inhibitor
Number of Participants With Demonstrated Improvement From Baseline on the Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall	20 Participants	23 Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Participants complete 12 weeks follow up included in this analysis.

UPSA-B is a validated performance-based measure to evaluate the impact of rivastigmine-mediated memory improvements on the ability to perform tasks required for day-to-day functioning in two subdomains of financial management and communication. The scale goes from (0-100) and high score indicates better functions. Comparison of difference in mean changes of UPSA-B from baseline to 12-week follow-up between two groups.

Outcome measures

Outcome measures
Measure	Rivastigmine n=49 Participants Rivastigmine transdermal patch Rivastigmine Transdermal Patch: Cholinesterase Inhibitor	Placebo n=45 Participants Placebo Rivastigmine Transdermal Patch: Cholinesterase Inhibitor
Twelve-week Change in University of California San Diego Performance-based Skills Assessment - Brief (UPSA-B)	-0.9 units on a scale Standard Deviation 6.4	3.3 units on a scale Standard Deviation 8.5

SECONDARY outcome

Timeframe: 12 week

PCL-M is a validated 17-item self-report measure of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) symptoms of PTSD.The PCL-M asks about problems in response to "stressful military experiences." Items are rated on a 5-point scale ranging from 1 ("not at all") to 5 ("extremely"). Higher score indicates more stressful. Comparison of difference in mean changes of PCL-M from baseline to 12-week follow-up between two groups.

Outcome measures

Outcome measures
Measure	Rivastigmine n=49 Participants Rivastigmine transdermal patch Rivastigmine Transdermal Patch: Cholinesterase Inhibitor	Placebo n=45 Participants Placebo Rivastigmine Transdermal Patch: Cholinesterase Inhibitor
Twelve-week Change in The PTSD Symptom Checklist-Military Version (PCL-M)	-1.4 units on a scale Standard Deviation 8.9	-4.4 units on a scale Standard Deviation 9.8

SECONDARY outcome

Timeframe: 12 week

Beck Depression Inventory-II (BDI-II) is a validated 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depressive symptoms. Each answer is scored on a scale value of 0 to 3. Higher score indicates more severe depression. To compare the differences in mean changes of BDI-II between two groups using two groups from baseline to week 12.

Outcome measures

Outcome measures
Measure	Rivastigmine n=49 Participants Rivastigmine transdermal patch Rivastigmine Transdermal Patch: Cholinesterase Inhibitor	Placebo n=45 Participants Placebo Rivastigmine Transdermal Patch: Cholinesterase Inhibitor
Twelve-week Change in Beck Depression Inventory-II (BDI-II)	-1.4 units on a scale Standard Deviation 8.8	-0.7 units on a scale Standard Deviation 9.2

Adverse Events

Rivastigmine

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rivastigmine n=49 participants at risk Rivastigmine transdermal patch Rivastigmine Transdermal Patch: Cholinesterase Inhibitor	Placebo n=45 participants at risk Placebo Rivastigmine Transdermal Patch: Cholinesterase Inhibitor
Musculoskeletal and connective tissue disorders Arthritis	2.0% 1/49 • Number of events 1 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).	0.00% 0/45 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
Injury, poisoning and procedural complications Femur fracture	2.0% 1/49 • Number of events 1 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).	0.00% 0/45 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
Gastrointestinal disorders Gastric perforation	0.00% 0/49 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).	2.2% 1/45 • Number of events 1 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
Infections and infestations Pilonidal cyst	0.00% 0/49 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).	2.2% 1/45 • Number of events 1 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
Psychiatric disorders post traumatic stress disorder	0.00% 0/49 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).	2.2% 1/45 • Number of events 1 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
Psychiatric disorders self serious ideation	2.0% 1/49 • Number of events 1 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).	0.00% 0/45 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
Psychiatric disorders Somnolence	2.0% 1/49 • Number of events 1 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).	0.00% 0/45 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
Psychiatric disorders Suicidal ideation	0.00% 0/49 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).	2.2% 1/45 • Number of events 1 • Adverse events were collected on study participants starting from when the first participant was enrolled, December 29, 2012 through June 16, 2016 (3 1/2 years). Adverse event (AE) and serious adverse event (SAE) data based on system organ classes and preferred terms which are derived from MedDRA (Medical Dictionary for Regulatory Activities) coding. MedDRA terminology is the international medical terminology developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).

Other adverse events

Additional Information

Tom Sindowski

Hines CSPCC

Phone: 708-202-5858

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place