Trial Outcomes & Findings for Naltrexone and Memantine Effects on Alcohol Drinking Behaviors (NCT NCT01519063)

Results Overview

Number of drinks consumed during the lab session (Day 7) after taking study medication, ranging from 0-12.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

75 participants

Primary outcome timeframe

Day 7

Results posted on

2020-03-09

Participant Flow

The number of participants enrolled was 75. However, 19 people did not start medication due to ineligibility or drop out, leaving 56 total participants.

Participant milestones

Participant milestones
Measure	Naltrexone and Memantine First Patients received Naltrexone and Memantine first in this arm.	Naltrexone and Placebo First Patients received Naltrexone and Placebo first in this arm.
Overall Study STARTED	26	30
Overall Study COMPLETED	19	25
Overall Study NOT COMPLETED	7	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Naltrexone and Memantine Effects on Alcohol Drinking Behaviors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Naltrexone and Memantine First n=26 Participants Patients in this arm received Naltrexone and Memantine first.	Naltrexone and Placebo First n=30 Participants Patients in this arm received Naltrexone and Placebo first.	Total n=56 Participants Total of all reporting groups
Age, Continuous	34 years STANDARD_DEVIATION 8.5 • n=5 Participants	33 years STANDARD_DEVIATION 9.3 • n=7 Participants	33 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	18 Participants n=7 Participants	33 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	16 Participants n=5 Participants	20 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized Non-Caucasian	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Total number of drinks over past 90 days	166 drinks STANDARD_DEVIATION 63 • n=5 Participants	165 drinks STANDARD_DEVIATION 1 • n=7 Participants	165 drinks STANDARD_DEVIATION 72 • n=5 Participants
Drinks per drinking day in past 90 days	7.2 drinks STANDARD_DEVIATION 2.5 • n=5 Participants	7.2 drinks STANDARD_DEVIATION 2.9 • n=7 Participants	7.2 drinks STANDARD_DEVIATION 2.7 • n=5 Participants
Percent of drinking days over past 90 days	78 percent of days STANDARD_DEVIATION 16 • n=5 Participants	75 percent of days STANDARD_DEVIATION 17 • n=7 Participants	76 percent of days STANDARD_DEVIATION 16 • n=5 Participants

PRIMARY outcome

Timeframe: Day 7

Number of drinks consumed during the lab session (Day 7) after taking study medication, ranging from 0-12.

Outcome measures

Outcome measures
Measure	Naltrexone and Memantine n=47 Participants Treatment with Naltrexone and memantine Naltrexone and memantine: Naltrexone 50mg memantine 20mg	Naltrexone and Placebo n=46 Participants Treatment with naltrexone and placebo Naltrexone and Placebo: Naltrexone 50 mg Placebo
Number of Drinks Consumed at Lab Session (Day 7)	4.11 drinks Standard Deviation 4.19	5.02 drinks Standard Deviation 4.32

PRIMARY outcome

Timeframe: 50-230 minutes after the priming drink during lab session

Craving for alcohol based on Alcohol Urge Questionnaire (AUQ, Bohn et al., 1995), which is an 8 item measurement of self-reported alcohol urges that has been shown to be strongly related to alcohol dependence severity. Each item is scored from 1 (strongly disagree) to 7 (strongly agree), with a higher score indicating higher craving. Assessed multiple times, starting at 50 minutes after priming drink until 230 minutes after priming drink. Higher craving scores (ranging from 0-56) are indicated by larger log-transformed AUC.

Outcome measures

Outcome measures
Measure	Naltrexone and Memantine n=47 Participants Treatment with Naltrexone and memantine Naltrexone and memantine: Naltrexone 50mg memantine 20mg	Naltrexone and Placebo n=46 Participants Treatment with naltrexone and placebo Naltrexone and Placebo: Naltrexone 50 mg Placebo
Craving AUC: Adlib Drinking Phase	7.62 log (units on a scale * minutes) Standard Deviation .54	7.75 log (units on a scale * minutes) Standard Deviation .55

PRIMARY outcome

Timeframe: 50-230 minutes after the priming drink during lab session

Brief Biphasic Alcohol Effects Scale-Stimulation subscale (BAES; Martin et al., 1993), measuring stimulation effects of alcohol. Seven items ranging from 0 (not at all) to extremely (10) with higher measurements indicating higher stimulation. Assessed multiple times, starting at 50 minutes after priming drink until 230 minutes after priming drink. Higher stimulation scores (ranging from 0-70) are indicated by larger log-transformed AUC.

Outcome measures

Outcome measures
Measure	Naltrexone and Memantine n=47 Participants Treatment with Naltrexone and memantine Naltrexone and memantine: Naltrexone 50mg memantine 20mg	Naltrexone and Placebo n=46 Participants Treatment with naltrexone and placebo Naltrexone and Placebo: Naltrexone 50 mg Placebo
Stimulation Response to Alcohol at Lab Session	4.78 log (units on a scale *minutes) Standard Deviation 3.51	4.93 log (units on a scale *minutes) Standard Deviation 3.45

PRIMARY outcome

Timeframe: 50-230 minutes after the priming drink during lab session

Brief Biphasic Alcohol Effects Scale-Sedation subscale (BAES; Martin et al., 1993), measuring sedation effects of alcohol. The seven items included on the sedation subscale range from 1 (not at all) to extremely (10) with higher measurements indicating higher sedation. Assessed multiple times, starting at 50 minutes after priming drink until 230 minutes after priming drink. Area Under the Curve was used to calculate the final score reported for the BAES. As a single summary measure, AUC, was calculated for BAES outcomes based on scores recorded at numerous time points throughout the adlib drinking session The calculation was based on the trapezoidal methods using times 50, 90, 110, 150, 170, 210, and 230 . Based on the distribution, each AUC was log-transformed. Higher AUC levels correspond to greater levels of sedation.

Outcome measures

Outcome measures
Measure	Naltrexone and Memantine n=47 Participants Treatment with Naltrexone and memantine Naltrexone and memantine: Naltrexone 50mg memantine 20mg	Naltrexone and Placebo n=46 Participants Treatment with naltrexone and placebo Naltrexone and Placebo: Naltrexone 50 mg Placebo
Sedation Response to Alcohol at Lab Session	5.42 log (units on a scale *minutes) Standard Deviation 2.97	5.34 log (units on a scale *minutes) Standard Deviation 3.08

PRIMARY outcome

Timeframe: 0-50 minutes after the priming drink

Craving for alcohol based on Alcohol Urge Questionnaire (AUQ, Bohn et al., 1995), which is an 8 item measurement of self-reported alcohol urges that has been shown to be strongly related to alcohol dependence severity. Each item is scored from 1 (strongly disagree) to 7 (strongly agree), with a higher score indicating higher craving. Craving for alcohol based on Alcohol Urge Questionnaire is calculated using Area Under the Curve (AUC). A single summary measure, AUC was calculated for AUQ outcomes based on scores recorded at numerous time points throughout the priming drink session. The calculation was based on the trapezoidal methods using times -20, 10, 20, 30, 40, 50 minutes before/after priming drink. Based on the distribution, each AUC was log-transformed. Higher AUC levels correspond to greater alcohol urge.

Outcome measures

Outcome measures
Measure	Naltrexone and Memantine n=47 Participants Treatment with Naltrexone and memantine Naltrexone and memantine: Naltrexone 50mg memantine 20mg	Naltrexone and Placebo n=46 Participants Treatment with naltrexone and placebo Naltrexone and Placebo: Naltrexone 50 mg Placebo
Craving AUC: Priming Dose Phase	6.81 log (units on a scale *minutes) Standard Deviation .55	6.84 log (units on a scale *minutes) Standard Deviation .57

PRIMARY outcome

Timeframe: 0-50 minutes after priming drink

Brief Biphasic Alcohol Effects Scale-Sedation subscale, measuring sedation effects of alcohol with higher measurements indicating higher sedation. Brief Biphasic Alcohol Effects Scale-Stimulation subscale (BAES; Martin et al., 1993), measuring stimulation effects of alcohol. Seven items ranging from 0 (not at all) to extremely (10) with higher measurements indicating higher stimulation. The subscale total range is 0-70, these scores are logged transformed.

Outcome measures

Outcome measures
Measure	Naltrexone and Memantine n=47 Participants Treatment with Naltrexone and memantine Naltrexone and memantine: Naltrexone 50mg memantine 20mg	Naltrexone and Placebo n=46 Participants Treatment with naltrexone and placebo Naltrexone and Placebo: Naltrexone 50 mg Placebo
Sedation Response to Alcohol: Priming Dose Phase	3.87 log (units on a scale) Standard Deviation 2.49	3.76 log (units on a scale) Standard Deviation 2.34

PRIMARY outcome

Timeframe: 0-50 minutes after priming drink

Brief Biphasic Alcohol Effects Scale-Stimulation subscale, measuring stimulation effects of alcohol with higher measurements indicating higher stimulation. Brief Biphasic Alcohol Effects Scale-Stimulation subscale (BAES; Martin et al., 1993), measuring stimulation effects of alcohol. Seven items ranging from 0 (not at all) to extremely (10) with higher measurements indicating higher stimulation. The subscale total range is 0-70, these scores are logged transformed.

Outcome measures

Outcome measures
Measure	Naltrexone and Memantine n=47 Participants Treatment with Naltrexone and memantine Naltrexone and memantine: Naltrexone 50mg memantine 20mg	Naltrexone and Placebo n=46 Participants Treatment with naltrexone and placebo Naltrexone and Placebo: Naltrexone 50 mg Placebo
Stimulation Response to Alcohol: Priming Dose Phase	3.20 log (units on a scale) Standard Deviation 2.84	3.43 log (units on a scale) Standard Deviation 2.71

Adverse Events

Naltrexone and Memantine

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Naltrexone and Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Naltrexone and Memantine n=47 participants at risk Treatment with Naltrexone and memantine Naltrexone and memantine: Naltrexone 50mg memantine 20mg	Naltrexone and Placebo n=46 participants at risk Treatment with naltrexone and placebo Naltrexone and Placebo: Naltrexone 50 mg Placebo
Gastrointestinal disorders Nausea	6.4% 3/47 • Adverse event data was collected at baseline and during the 7 days of medication, as well as at the one week follow up	6.5% 3/46 • Adverse event data was collected at baseline and during the 7 days of medication, as well as at the one week follow up

Additional Information

Dana Cavallo, Assistant Professor

Yale University

Phone: 203974-7607

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place