Trial Outcomes & Findings for Phenytoin for Memory Impairment Secondary to Megestrol (NCT NCT02595723)
NCT ID: NCT02595723
Last Updated: 2019-09-09
Results Overview
Rey Auditory Verbal Learning Test (RAVLT) is a test of verbal learning and declarative memory. During the test, 15 nouns that are read aloud for 5 consecutive trials. Each trial is followed by a free recall test (participant is asked to recall the words that were just read to them). The sum of correctly recalled words across 5 trials is called the total raw score. The raw scores on the total recall (number of words correct across trials 1-5) are converted to standardized T-scores (Mean=50; SD=10; range 20-100) based on participant age and gender. The scores below are presented as T-scores, with higher scores indicative of better performance.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
21 participants
Primary outcome timeframe
4 days after intervention administration
Results posted on
2019-09-09
Participant Flow
35 patients were screened for eligibility between July 2015 and September 2016.
21 of 35 participants were randomized. Of those not randomized, 14 did not meet inclusion criteria.
Participant milestones
| Measure |
Ph + Meg, Then Pl + Meg, Then Pl + Pl
Participants first received pretreatment with Phenytoin 200 mg capsule twice/day for one day. Participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
Following first 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
Following second 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
|
Pl + Meg, Then Pl + Pl, Then Ph + Meg
Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
Following first 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
Following second 21-day washout, participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
|
Pl + Pl, Then Ph + Meg, Then Pl + Meg
Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
Following first 21-day washout, participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
Following second 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
|
|---|---|---|---|
|
First Intervention (4 Days)
STARTED
|
8
|
6
|
7
|
|
First Intervention (4 Days)
COMPLETED
|
8
|
6
|
7
|
|
First Intervention (4 Days)
NOT COMPLETED
|
0
|
0
|
0
|
|
First Washout (21 Days)
STARTED
|
8
|
6
|
7
|
|
First Washout (21 Days)
COMPLETED
|
6
|
6
|
7
|
|
First Washout (21 Days)
NOT COMPLETED
|
2
|
0
|
0
|
|
Second Intervention (4 Days)
STARTED
|
6
|
6
|
7
|
|
Second Intervention (4 Days)
COMPLETED
|
6
|
6
|
7
|
|
Second Intervention (4 Days)
NOT COMPLETED
|
0
|
0
|
0
|
|
Second Washout (21 Days)
STARTED
|
6
|
6
|
7
|
|
Second Washout (21 Days)
COMPLETED
|
6
|
5
|
7
|
|
Second Washout (21 Days)
NOT COMPLETED
|
0
|
1
|
0
|
|
Third Intervention (4 Days)
STARTED
|
6
|
5
|
7
|
|
Third Intervention (4 Days)
COMPLETED
|
6
|
5
|
7
|
|
Third Intervention (4 Days)
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Ph + Meg, Then Pl + Meg, Then Pl + Pl
Participants first received pretreatment with Phenytoin 200 mg capsule twice/day for one day. Participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
Following first 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
Following second 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
|
Pl + Meg, Then Pl + Pl, Then Ph + Meg
Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
Following first 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
Following second 21-day washout, participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
|
Pl + Pl, Then Ph + Meg, Then Pl + Meg
Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
Following first 21-day washout, participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
Following second 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
|
|---|---|---|---|
|
First Washout (21 Days)
Withdrawal by Subject
|
1
|
0
|
0
|
|
First Washout (21 Days)
Lost to Follow-up
|
1
|
0
|
0
|
Baseline Characteristics
Phenytoin for Memory Impairment Secondary to Megestrol
Baseline characteristics by cohort
| Measure |
Ph + Meg, Then Pl + Meg, Then Pl + Pl
n=8 Participants
Participants first received pretreatment with Phenytoin 200 mg capsule twice/day for one day. Participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
Following first 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
Following second 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
|
Pl + Meg, Then Pl + Pl, Then Ph + Meg
n=6 Participants
Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
Following first 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
Following second 21-day washout, participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
|
Pl + Pl, Then Ph + Meg, Then Pl + Meg
n=7 Participants
Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
Following first 21-day washout, participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
Following second 21-day washout, participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
27.63 years
STANDARD_DEVIATION 3.97 • n=93 Participants
|
30.50 years
STANDARD_DEVIATION 7.94 • n=4 Participants
|
30.71 years
STANDARD_DEVIATION 9.20 • n=27 Participants
|
29.48 years
STANDARD_DEVIATION 7.05 • n=483 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
14 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
12 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: 4 days after intervention administrationRey Auditory Verbal Learning Test (RAVLT) is a test of verbal learning and declarative memory. During the test, 15 nouns that are read aloud for 5 consecutive trials. Each trial is followed by a free recall test (participant is asked to recall the words that were just read to them). The sum of correctly recalled words across 5 trials is called the total raw score. The raw scores on the total recall (number of words correct across trials 1-5) are converted to standardized T-scores (Mean=50; SD=10; range 20-100) based on participant age and gender. The scores below are presented as T-scores, with higher scores indicative of better performance.
Outcome measures
| Measure |
Phenytoin, Then Megestrol
n=20 Participants
Participants first received pretreatment with Phenytoin 200 mg capsule twice/day for one day. Participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
|
Placebo, Then Megestrol
n=19 Participants
Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
|
Placebo, Then Placebo
n=19 Participants
Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
|
|---|---|---|---|
|
Rey Auditory Verbal Learning Test (RAVLT)
|
51.89 T-scores
Standard Deviation 8.08
|
45.90 T-scores
Standard Deviation 10.40
|
48.37 T-scores
Standard Deviation 10.42
|
Adverse Events
Phenytoin, Then Megestrol
Serious events: 0 serious events
Other events: 5 other events
Deaths: 1 deaths
Placebo, Then Megestrol
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo, Then Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Phenytoin, Then Megestrol
n=20 participants at risk
Participants first received pretreatment with Phenytoin 200 mg capsule twice/day for one day. Participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days.
|
Placebo, Then Megestrol
n=19 participants at risk
Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days.
|
Placebo, Then Placebo
n=19 participants at risk
Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/20 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
5.3%
1/19 • Number of events 1 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/20 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
5.3%
1/19 • Number of events 1 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
|
Ear and labyrinth disorders
Transient hearing loss
|
5.0%
1/20 • Number of events 1 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
|
Ear and labyrinth disorders
Tinnitus
|
5.0%
1/20 • Number of events 1 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
|
Nervous system disorders
Mild cognitive impairment
|
5.0%
1/20 • Number of events 1 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
|
Musculoskeletal and connective tissue disorders
Knee injury
|
5.0%
1/20 • Number of events 1 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
|
Reproductive system and breast disorders
Irregular menses
|
0.00%
0/20 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
10.5%
2/19 • Number of events 2 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
|
Social circumstances
Fall
|
5.0%
1/20 • Number of events 1 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
|
Infections and infestations
Cold
|
0.00%
0/20 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
0.00%
0/19 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
5.3%
1/19 • Number of events 1 • 4 days for each intervention.
The safety population included all participants who received at least one dose of intervention.
|
Additional Information
E. Sherwood Brown, M.D., Ph.D.
UT Southwestern Medical Center
Phone: 214-645-6950
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place