Trial Outcomes & Findings for Efficacy of Levetiracetam in Cocaine-Abusing Methadone Maintained Patients (NCT NCT00577005)
NCT ID: NCT00577005
Last Updated: 2018-01-17
Results Overview
The primary outcome variable was the change from baseline to week 13 of the thrice weekly cocaine-free urine scores. In this repeated ordinal variable, 0 represented all 3 urine samples submitted by the subject as positives, 1 represented some urine samples submitted by the subject were negative, and 2 represented all 3 urine samples submitted by the subjects were negative for cocaine. Balancing the distribution between these categories improved the models for the analysis of repeated ordinal data. Data is summarized as number of participant that were cocaine free urine (score 2) per week by group.
COMPLETED
PHASE2
28 participants
Weekly from baseline to week 12
2018-01-17
Participant Flow
Thirty three cocaine and opioid dependent treatment seeking individuals were recruited by newspaper advertising, word-of -mouth and referrals from community-based substance abuse clinics. Research staff obtained informed consent and subjects were evaluated for study eligibility.
Twenty eight subjects were assigned to treatment groups while concurrently receiving treatment with methadone. Randomization was balanced with urn procedure on gender and severity of cocaine use score.
Participant milestones
| Measure |
Levetiracetam 3000mg + Methadone
Participants were inducted onto methadone during the first week of study participation and then started on Levetiracetam 500mg in the mornings of the first day of week 2. The dose was titrated every third day on a twice day schedule, until the target dose of 3000mg/day was achieved or to the subject's maximum tolerated dose (MTD) by week 4.
Levetiracetam: 3000mg orally everyday for 12 weeks
|
Levetiracetam 0mg + Methadone
Participants were inducted onto methadone during the first week of study participation. Matching placebo capsules were started on week 2. The placebo capsules were given on a twice a day schedule until week 13.
Placebo: Placebo orally everyday for 13 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
12
|
|
Overall Study
COMPLETED
|
11
|
9
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
Reasons for withdrawal
| Measure |
Levetiracetam 3000mg + Methadone
Participants were inducted onto methadone during the first week of study participation and then started on Levetiracetam 500mg in the mornings of the first day of week 2. The dose was titrated every third day on a twice day schedule, until the target dose of 3000mg/day was achieved or to the subject's maximum tolerated dose (MTD) by week 4.
Levetiracetam: 3000mg orally everyday for 12 weeks
|
Levetiracetam 0mg + Methadone
Participants were inducted onto methadone during the first week of study participation. Matching placebo capsules were started on week 2. The placebo capsules were given on a twice a day schedule until week 13.
Placebo: Placebo orally everyday for 13 weeks
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
Baseline Characteristics
Efficacy of Levetiracetam in Cocaine-Abusing Methadone Maintained Patients
Baseline characteristics by cohort
| Measure |
Levetiracetam
n=16 Participants
Levetiracetam tablets
levetiracetam: The participants will start receiving Levetiracetam 500mg in the mornings of the first day on week 2. The dose will be titrated every third day, until the target dose of 3000mg/day is achieved by week 4. The study medication must be titrated to 3000 mg/day or to the subject's maximum tolerated dose (MTD). The physician overseeing this titration as well as all study staff will be blind to the subject's medication administration. The medication will be discontinued over a two-week period.
|
Placebo
n=12 Participants
matching placebo
Placebo
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
35.1 years
STANDARD_DEVIATION 10.7 • n=99 Participants
|
33.6 years
STANDARD_DEVIATION 9.6 • n=107 Participants
|
34.4 years
STANDARD_DEVIATION 10.1 • n=206 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
15 participants
n=99 Participants
|
11 participants
n=107 Participants
|
26 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
African American
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Weekly from baseline to week 12Population: The intent-to-treat (ITT) sample were the 28 subjects were randomized and received one dose of study medication.
The primary outcome variable was the change from baseline to week 13 of the thrice weekly cocaine-free urine scores. In this repeated ordinal variable, 0 represented all 3 urine samples submitted by the subject as positives, 1 represented some urine samples submitted by the subject were negative, and 2 represented all 3 urine samples submitted by the subjects were negative for cocaine. Balancing the distribution between these categories improved the models for the analysis of repeated ordinal data. Data is summarized as number of participant that were cocaine free urine (score 2) per week by group.
Outcome measures
| Measure |
Levetiracetam 3000mg + Methadone
n=16 Participants
Participants were inducted onto methadone during the first week of study participation and then started on Levetiracetam 500mg in the mornings of the first day of week 2. The dose was titrated every third day on a twice day schedule, until the target dose of 3000mg/day was achieved or to the subject's maximum tolerated dose (MTD) by week 4.
Levetiracetam: 3000mg orally everyday for 12 weeks
|
Levetiracetam 0mg + Methadone
n=12 Participants
Participants were inducted onto methadone during the first week of study participation. Matching placebo capsules were started on week 2. The placebo capsules were given on a twice a day schedule until week 13.
Placebo: Placebo orally everyday for 13 weeks
|
|---|---|---|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 3
|
5 participants that were cocaine free
|
4 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 8
|
4 participants that were cocaine free
|
3 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
Baseline
|
6 participants that were cocaine free
|
0 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 1
|
3 participants that were cocaine free
|
2 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 2
|
6 participants that were cocaine free
|
3 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 4
|
5 participants that were cocaine free
|
4 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 5
|
5 participants that were cocaine free
|
2 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 6
|
3 participants that were cocaine free
|
4 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 7
|
3 participants that were cocaine free
|
3 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 9
|
4 participants that were cocaine free
|
4 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 10
|
5 participants that were cocaine free
|
4 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 11
|
5 participants that were cocaine free
|
5 participants that were cocaine free
|
|
Change of Thrice Weekly Cocaine Free Urine Toxicology From Week 1 to 13
week 12
|
5 participants that were cocaine free
|
5 participants that were cocaine free
|
SECONDARY outcome
Timeframe: Weekly from baseline to week 12Population: The intent-to-treat (ITT) sample were the 28 subjects were randomized and received one dose of study medication.
The secondary outcome variable was the change from baseline to week 13 of the thrice weekly opioid-free urine scores. In this repeated ordinal variable, 0 represented all 3 urines samples submitted by the subject as positives, 1 represented some urine samples submitted by the subject were negative, and 2 represented all 3 urines samples submitted by the subjects were negative for opioids excluding methadone. Balancing the distribution between these categories improved the models for the analysis of repeated ordinal data. Data summarized by number of participants who were had opioid free urine samples (score 2) per week by group.
Outcome measures
| Measure |
Levetiracetam 3000mg + Methadone
n=16 Participants
Participants were inducted onto methadone during the first week of study participation and then started on Levetiracetam 500mg in the mornings of the first day of week 2. The dose was titrated every third day on a twice day schedule, until the target dose of 3000mg/day was achieved or to the subject's maximum tolerated dose (MTD) by week 4.
Levetiracetam: 3000mg orally everyday for 12 weeks
|
Levetiracetam 0mg + Methadone
n=12 Participants
Participants were inducted onto methadone during the first week of study participation. Matching placebo capsules were started on week 2. The placebo capsules were given on a twice a day schedule until week 13.
Placebo: Placebo orally everyday for 13 weeks
|
|---|---|---|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 1
|
5 participants with opioid free urine
|
3 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
Baseline
|
4 participants with opioid free urine
|
4 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 2
|
7 participants with opioid free urine
|
4 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 3
|
5 participants with opioid free urine
|
6 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 4
|
6 participants with opioid free urine
|
3 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 5
|
8 participants with opioid free urine
|
4 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 6
|
7 participants with opioid free urine
|
4 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 7
|
5 participants with opioid free urine
|
6 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 8
|
5 participants with opioid free urine
|
4 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 9
|
6 participants with opioid free urine
|
4 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 10
|
6 participants with opioid free urine
|
5 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 11
|
8 participants with opioid free urine
|
5 participants with opioid free urine
|
|
Change of Thrice Weekly Opioid Free Urine Toxicology From Week 1 to 13
week 12
|
5 participants with opioid free urine
|
5 participants with opioid free urine
|
SECONDARY outcome
Timeframe: Week 13Population: Intent-treat-sample (ITT) that was inducted onto methadone and received one dose of study medication on week 2.
Weekly from week 1 to 13
Outcome measures
| Measure |
Levetiracetam 3000mg + Methadone
n=16 Participants
Participants were inducted onto methadone during the first week of study participation and then started on Levetiracetam 500mg in the mornings of the first day of week 2. The dose was titrated every third day on a twice day schedule, until the target dose of 3000mg/day was achieved or to the subject's maximum tolerated dose (MTD) by week 4.
Levetiracetam: 3000mg orally everyday for 12 weeks
|
Levetiracetam 0mg + Methadone
n=12 Participants
Participants were inducted onto methadone during the first week of study participation. Matching placebo capsules were started on week 2. The placebo capsules were given on a twice a day schedule until week 13.
Placebo: Placebo orally everyday for 13 weeks
|
|---|---|---|
|
Treatment Retention
|
13 participants
|
9 participants
|
SECONDARY outcome
Timeframe: Weekly from baseline to week 12Population: Intent to treat sample
Weekly cocaine craving was measure at intake and weekly after with the Visual Analog Scale (VAS) of the Cocaine Selective Severity Assessment. The VAS measures the intensity of cocaine craving with a scale from 0 (No desire at all) to 7 (Unable to resist), and frequency of cocaine craving in the previous 24 hours with a scale from 0 ( never) to 7 ( all the time). The scale is totaled for a maximum number of 14, the minimum is 0. (Kampman et al., 1998; Mulvaney et al., 1999).
Outcome measures
| Measure |
Levetiracetam 3000mg + Methadone
n=16 Participants
Participants were inducted onto methadone during the first week of study participation and then started on Levetiracetam 500mg in the mornings of the first day of week 2. The dose was titrated every third day on a twice day schedule, until the target dose of 3000mg/day was achieved or to the subject's maximum tolerated dose (MTD) by week 4.
Levetiracetam: 3000mg orally everyday for 12 weeks
|
Levetiracetam 0mg + Methadone
n=12 Participants
Participants were inducted onto methadone during the first week of study participation. Matching placebo capsules were started on week 2. The placebo capsules were given on a twice a day schedule until week 13.
Placebo: Placebo orally everyday for 13 weeks
|
|---|---|---|
|
Cocaine Craving
week 8
|
2.80 units on a scale
Standard Error 1.340
|
3.60 units on a scale
Standard Error 1.454
|
|
Cocaine Craving
week 11
|
2.09 units on a scale
Standard Error 1.031
|
4.20 units on a scale
Standard Error 1.800
|
|
Cocaine Craving
week 12
|
3.27 units on a scale
Standard Error 1.579
|
4.22 units on a scale
Standard Error 1.985
|
|
Cocaine Craving
Baseline
|
7.19 units on a scale
Standard Error 1.512
|
6.50 units on a scale
Standard Error 1.617
|
|
Cocaine Craving
week 1
|
4.13 units on a scale
Standard Error 1.373
|
5.75 units on a scale
Standard Error 1.488
|
|
Cocaine Craving
week 2
|
2.64 units on a scale
Standard Error 1.097
|
2.83 units on a scale
Standard Error 1.192
|
|
Cocaine Craving
week 3
|
2.13 units on a scale
Standard Error 1.041
|
3.42 units on a scale
Standard Error 1.417
|
|
Cocaine Craving
week 4
|
2.13 units on a scale
Standard Error 0.985
|
3.17 units on a scale
Standard Error 1.140
|
|
Cocaine Craving
week 5
|
2.53 units on a scale
Standard Error 0.904
|
3.27 units on a scale
Standard Error 1.556
|
|
Cocaine Craving
week 6
|
3.00 units on a scale
Standard Error 1.144
|
2.18 units on a scale
Standard Error 1.278
|
|
Cocaine Craving
week 7
|
2.67 units on a scale
Standard Error 1.484
|
3.18 units on a scale
Standard Error 1.470
|
|
Cocaine Craving
week 9
|
2.33 units on a scale
Standard Error 1.124
|
3.09 units on a scale
Standard Error 1.486
|
|
Cocaine Craving
week 10
|
2.18 units on a scale
Standard Error 1.306
|
3.55 units on a scale
Standard Error 1.603
|
Adverse Events
Levetiracetam 3000mg + Methadone
Levetiracetam 0mg + Methadone
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Levetiracetam 3000mg + Methadone
n=16 participants at risk
Participants were inducted onto methadone during the first week of study participation and then started on Levetiracetam 500mg in the mornings of the first day of week 2. The dose was titrated every third day on a twice day schedule, until the target dose of 3000mg/day was achieved or to the subject's maximum tolerated dose (MTD) by week 4.
Levetiracetam: 3000mg orally everyday for 12 weeks
|
Levetiracetam 0mg + Methadone
n=12 participants at risk
Participants were inducted onto methadone during the first week of study participation. Matching placebo capsules were started on week 2. The placebo capsules were given on a twice a day schedule until week 13.
Placebo: Placebo orally everyday for 13 weeks
|
|---|---|---|
|
Hepatobiliary disorders
Hepatitis
|
6.2%
1/16 • Number of events 1 • Adverse events were collected from week 1 to week 13
|
0.00%
0/12 • Adverse events were collected from week 1 to week 13
|
|
Infections and infestations
Infection
|
6.2%
1/16 • Number of events 1 • Adverse events were collected from week 1 to week 13
|
16.7%
2/12 • Number of events 2 • Adverse events were collected from week 1 to week 13
|
|
Musculoskeletal and connective tissue disorders
Cut finger-accident
|
0.00%
0/16 • Adverse events were collected from week 1 to week 13
|
8.3%
1/12 • Number of events 1 • Adverse events were collected from week 1 to week 13
|
Additional Information
Gerardo Gonzalez, MD
University of Massachusetts Medical School
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place