Cocaine Dependence, Cocaine Addiction, Cocaine Abuse, Cocaine-Related Disorders
Conditions
Keywords
Cocaine, Clavulanic Acid
Brief summary
The main purpose of this study is to determine if it is safe to use the study drug, clavulanic acid, in combination with cocaine. In this study, subjects will receive intravenous (i.v.) cocaine and the study drug, clavulanic acid. The safety of clavulanic acid is being studied so future studies can be done to find out if this drug is helpful in treating cocaine dependence. Currently, there is no available medication treatment for cocaine dependence.
Detailed description
This is a prospective, placebo controlled inpatient crossover safety study of 3 doses (250 mg/day, 500 mg/day, 750 mg/day) of CLAV with an intravenous infusion of cocaine 40 mg. Subjects will be non-treatment seeking experienced cocaine dependent adults, ages 18-65 (N=12 completers, 21 estimated to enroll). Subjects will undergo a washout of the study drug for 5 half-lives between study drug administration sessions. The primary objective will be to determine whether there are clinically significant adverse interactions between CLAV (250 mg/day; 500 mg/day; 750 mg/day) and intravenously administered cocaine in healthy, non-treatment seeking adults with cocaine use disorder.
Interventions
DRUGClavulanic acid
Clavulanic acid will be administered orally in 250mg capsules
DRUGIntravenous cocaine
20/40mg Cocaine will be administered by IV
DRUGPlacebo
Placebo will be administered orally in capsules identical to CLAV and be filled with crystalline microcellulose
Sponsors
National Institute on Drug Abuse (NIDA)
University of Pennsylvania
Temple University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Meet Diagnostic and Statistical Manual of Mental Disorders Fifth Edition criteria for cocaine use disorder, moderate to severe. * Be a non-treatment seeking cocaine user. * If female and of childbearing potential, must have a negative pregnancy test within 48 hours of beginning the study and be willing to use acceptable contraception or be abstinent for 14 days prior to study, through the entire study and 30 days after study participation.
Exclusion criteria
* Be seeking treatment for substance abuse. (For full inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Electrocardiogram (ECG) Following IV Cocaine With and Without CLAV Dosing | 4 Days (Study Days 2, 3, 4, 5) | ECG was done 15 min after IV cocaine infusion (following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg). The interval between the Q wave and the T wave, corrected (QTc) is reported. |
| Number of Participants With Severe Adverse Events (AEs) | 6 Days (Study Days 1, 2, 3, 4, 5, 10) | Rates of occurrence of serious adverse events across the different treatments: Day 1-IV cocaine only; Day 2.3 and 4 treatment with either PBO, CLAV 250mg or CLAV 500mg depending on randomization; Day 5 CLAV 750mg, Day 10 Follow-up appointment See Adverse Event section for reporting of mild-moderate AEs. |
| Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing | 4 Days (Study Days 2, 3, 4, 5) | IV cocaine was infused 1 hour following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg and vital signs were checked at -15min,-10min, -5 min preinfusion of IV cocaine and then every 2 min for the first 30 minutes, then every 15min through 150 minutes post-infusion. The mean heart rate (HR) at 2 minutes post IV cocaine infusion and the maximum (max) change in heart rate from baseline pre-infusion are reported (peak heart rate post-infusion minus baseline heart rate pre-infusion) are reported. |
| Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | 4 Days (Study Days 2, 3, 4, 5) | IV cocaine was infused 1 hour following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg and vital signs were checked at -15min,-10min, -5 min pre-infusion of IV cocaine and then every 2 min for the first 30 minutes, then every 15min through 150 minutes post-infusion. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 2 minutes post IV cocaine infusion are reported. Also, the maximum (max) change in SBP snd DBP from baseline pre-infusion are reported (peak SBP or DBP post-infusion minus baseline SBP or DBP pre-infusion) are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter of Cocaine-concentration | 3 Days (Study Days 2, 3, 4) | Cocaine concentrations are reported at 10 min and 30 minutes after cocaine infusion (70 and 90 minutes after administration of placebo (PBO), CLAV 250mg or CLAV 500mg). |
| Clavulanic Acid (CLAV) Concentrations Following CLAV 250mg and CLAV 500mg Doses | 3 Days (Study Days 2, 3, 4) | CLAV concentrations were measured 40 min and 70 min after ingestion of CLAV 250 mg or 500 mg. (The 70 min time point is 10 min after the IV cocaine infusion).The 250mg dose and the 500mg dose were given on different days per the randomization protocol: the 250mg dose was given on either day 2 or 3 and the 500mg dose was given on either day 3 or 4. The lowest level of detection of CLAV is 40ng/ml. A non-detectable level is reported as 0. |
| Difference in CLAV Concentrations Between the 250mg and 500mg CLAV Doses | 3 days (Day 2, 3, 4) | The CLAV concentration after ingestion of 250mg CLAV minus the CLAV PK level after the 500 mg dose is reported at 40min and 70 min after ingestion |
| Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 10 minutes pre-infusion and 10, 15, 30 and 45 min after cocaine infusion on Study Days 2, 3, and 4 | Pupil Diameter (mm) was measured 10 minutes pre-infusion and 10, 15, 30 and 45 min after cocaine infusion. Cocaine infusion was done 1 hour following ingestion of placebo (day 2), CLAV 250 mg (day3), or CLAV 500 mg (day 4). Results are reported as median pupil diameter (mm) with interquartile range at different time points relative to the cocaine infusion as noted. |
Countries
United States
Participant flow
Recruitment details
This was an inpatient study at Temple University, Episcopal Hospital in Philadelphia, Pennsylvania with subjects recruited between 10/24/2016 and 6/04/2018.
Pre-assignment details
10 subjects were randomized to one of three treatment arms in a double masked method.
Participants by arm
| Arm | Count |
|---|---|
| Clavulanic Acid (CLAV) 250mg, CLAV 500mg Then Placebo (PBO) Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Clavulanic Acid 250 mg (low dose); Day #3: Clavulanic Acid 500 mg; Day #4: Placebo
Clavulanic acid
Intravenous cocaine
Placebo | 3 |
| CLAV 250mg, PBO, Then CLAV 500mg Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Clavulanic Acid 250 mg (low dose); Day #3: Placebo; Day #4: Clavulanic Acid 500 mg
Clavulanic acid
Intravenous cocaine
Placebo | 3 |
| PBO, CLAV 250mg Then CLAV 500mg Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Placebo; Day #3: Clavulanic Acid 250 mg (low dose); Day #4: Clavulanic Acid 500 mg
Clavulanic acid
Intravenous cocaine
Placebo | 4 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Added 750mg Dose of CLAV (Day 5) | Physician Decision | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Clavulanic Acid (CLAV) 250mg, CLAV 500mg Then Placebo (PBO) | CLAV 250mg, PBO, Then CLAV 500mg | PBO, CLAV 250mg Then CLAV 500mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
| Age, Continuous | 50 years | 53 years | 51 years | 51 years |
| Education Level | 3 Participants | 1 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 4 participants | 10 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 5 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 5 / 10 | 4 / 10 | 3 / 10 | 3 / 10 | 2 / 5 | 5 / 10 | 4 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 5 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing
IV cocaine was infused 1 hour following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg and vital signs were checked at -15min,-10min, -5 min preinfusion of IV cocaine and then every 2 min for the first 30 minutes, then every 15min through 150 minutes post-infusion. The mean heart rate (HR) at 2 minutes post IV cocaine infusion and the maximum (max) change in heart rate from baseline pre-infusion are reported (peak heart rate post-infusion minus baseline heart rate pre-infusion) are reported.
Time frame: 4 Days (Study Days 2, 3, 4, 5)
Population: 10 participants were randomized to receive PBO or CLAV 250mg or 500mg on days 2,3 and 4 followed one hour later by IV infusion of cocaine. Part way through the study, a 5th day was added giving CLAV 750mg 1hr before the cocaine infusion (Protocol V2.3). Five participants were eligible for Day 5 but one had technical issues with the cocaine infusion and did not receive the full cocaine dose, so that subject is excluded from the report of day 5 effects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Day 1 - IV Cocaine Only | Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing | HR at 2 min | 82.2 beats per minute | Standard Deviation 14.7 |
| Day 1 - IV Cocaine Only | Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing | Max change in HR from baseline | 26.3 beats per minute | Standard Deviation 22.6 |
| Placebo (PBO) | Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing | Max change in HR from baseline | 29.8 beats per minute | Standard Deviation 19.2 |
| Placebo (PBO) | Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing | HR at 2 min | 78.0 beats per minute | Standard Deviation 5.7 |
| CLAV 250mg | Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing | HR at 2 min | 86.8 beats per minute | Standard Deviation 13 |
| CLAV 250mg | Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing | Max change in HR from baseline | 32.0 beats per minute | Standard Deviation 26.3 |
| CLAV 500mg | Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing | HR at 2 min | 91.0 beats per minute | Standard Deviation 14.7 |
| CLAV 500mg | Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing | Max change in HR from baseline | 27.7 beats per minute | Standard Deviation 24.7 |
Primary
Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing
IV cocaine was infused 1 hour following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg and vital signs were checked at -15min,-10min, -5 min pre-infusion of IV cocaine and then every 2 min for the first 30 minutes, then every 15min through 150 minutes post-infusion. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 2 minutes post IV cocaine infusion are reported. Also, the maximum (max) change in SBP snd DBP from baseline pre-infusion are reported (peak SBP or DBP post-infusion minus baseline SBP or DBP pre-infusion) are reported.
Time frame: 4 Days (Study Days 2, 3, 4, 5)
Population: 10 participants were randomized to receive PBO or CLAV 250mg or 500mg on days 2,3 and 4 followed one hour later by IV infusion of cocaine. Part way through the study, a 5th day was added giving CLAV 750mg 1hr before the cocaine infusion (Protocol V2.3). Five participants were eligible for Day 5 but one had technical issues with the cocaine infusion and did not receive the full cocaine dose, so that subject is excluded from the report of day 5 effects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Day 1 - IV Cocaine Only | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | SBP at 2 min | 138.8 mm Hg | Standard Deviation 14.8 |
| Day 1 - IV Cocaine Only | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | Max change in SBP | 21.6 mm Hg | Standard Deviation 13 |
| Day 1 - IV Cocaine Only | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | DBP at 2 mim | 88.5 mm Hg | Standard Deviation 4.6 |
| Day 1 - IV Cocaine Only | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | Max change in DBP | 12.1 mm Hg | Standard Deviation 2.7 |
| Placebo (PBO) | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | SBP at 2 min | 135.0 mm Hg | Standard Deviation 15.4 |
| Placebo (PBO) | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | DBP at 2 mim | 88.8 mm Hg | Standard Deviation 11.2 |
| Placebo (PBO) | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | Max change in DBP | 13.3 mm Hg | Standard Deviation 4.1 |
| Placebo (PBO) | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | Max change in SBP | 23.5 mm Hg | Standard Deviation 11.3 |
| CLAV 250mg | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | DBP at 2 mim | 89.5 mm Hg | Standard Deviation 7.2 |
| CLAV 250mg | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | SBP at 2 min | 140.0 mm Hg | Standard Deviation 13.6 |
| CLAV 250mg | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | Max change in DBP | 12.6 mm Hg | Standard Deviation 5.1 |
| CLAV 250mg | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | Max change in SBP | 18.4 mm Hg | Standard Deviation 8.9 |
| CLAV 500mg | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | SBP at 2 min | 137.8 mm Hg | Standard Deviation 15.5 |
| CLAV 500mg | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | Max change in SBP | 20.9 mm Hg | Standard Deviation 16.4 |
| CLAV 500mg | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | DBP at 2 mim | 87.8 mm Hg | Standard Deviation 10 |
| CLAV 500mg | Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing | Max change in DBP | 12.7 mm Hg | Standard Deviation 3.9 |
Primary
Electrocardiogram (ECG) Following IV Cocaine With and Without CLAV Dosing
ECG was done 15 min after IV cocaine infusion (following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg). The interval between the Q wave and the T wave, corrected (QTc) is reported.
Time frame: 4 Days (Study Days 2, 3, 4, 5)
Population: 10 participants were randomized to receive PBO or CLAV 250mg or 500mg on days 2,3 and 4 followed one hour later by IV infusion of cocaine. Part way through the study, a 5th day was added giving CLAV 750mg 1hr before the cocaine infusion (Protocol V2.3). Five participants were eligible for Day 5 but one had technical issues with the cocaine infusion and did not receive the full cocaine dose, so that subject is excluded from the report of day 5 effects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 - IV Cocaine Only | Electrocardiogram (ECG) Following IV Cocaine With and Without CLAV Dosing | 431.8 ms | Standard Deviation 16.6 |
| Placebo (PBO) | Electrocardiogram (ECG) Following IV Cocaine With and Without CLAV Dosing | 432.3 ms | Standard Deviation 19.9 |
| CLAV 250mg | Electrocardiogram (ECG) Following IV Cocaine With and Without CLAV Dosing | 430.5 ms | Standard Deviation 16.3 |
| CLAV 500mg | Electrocardiogram (ECG) Following IV Cocaine With and Without CLAV Dosing | 431.3 ms | Standard Deviation 14.8 |
Primary
Number of Participants With Severe Adverse Events (AEs)
Rates of occurrence of serious adverse events across the different treatments: Day 1-IV cocaine only; Day 2.3 and 4 treatment with either PBO, CLAV 250mg or CLAV 500mg depending on randomization; Day 5 CLAV 750mg, Day 10 Follow-up appointment See Adverse Event section for reporting of mild-moderate AEs.
Time frame: 6 Days (Study Days 1, 2, 3, 4, 5, 10)
Population: Participants were adults (18-65) with current cocaine use disorder who were recruited from the greater Philadelphia area.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Day 1 - IV Cocaine Only | Number of Participants With Severe Adverse Events (AEs) | 0 Participants |
| Placebo (PBO) | Number of Participants With Severe Adverse Events (AEs) | 0 Participants |
| CLAV 250mg | Number of Participants With Severe Adverse Events (AEs) | 0 Participants |
| CLAV 500mg | Number of Participants With Severe Adverse Events (AEs) | 0 Participants |
| Day 5--CLAV 750mg | Number of Participants With Severe Adverse Events (AEs) | 0 Participants |
| Day 10--Follow up | Number of Participants With Severe Adverse Events (AEs) | 0 Participants |
Secondary
Clavulanic Acid (CLAV) Concentrations Following CLAV 250mg and CLAV 500mg Doses
CLAV concentrations were measured 40 min and 70 min after ingestion of CLAV 250 mg or 500 mg. (The 70 min time point is 10 min after the IV cocaine infusion).The 250mg dose and the 500mg dose were given on different days per the randomization protocol: the 250mg dose was given on either day 2 or 3 and the 500mg dose was given on either day 3 or 4. The lowest level of detection of CLAV is 40ng/ml. A non-detectable level is reported as 0.
Time frame: 3 Days (Study Days 2, 3, 4)
Population: 10 subjects received 250mg and 500mg (randomized to different days) but samples for one subject was unusable. A second subject vomited 5 min after both the 250mg dose and the 500mg dose and levels were undetectable; this subject was excluded from analysis. This reports results of 8 subjects.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 1 - IV Cocaine Only | Clavulanic Acid (CLAV) Concentrations Following CLAV 250mg and CLAV 500mg Doses | 0.036 mg/L |
| Placebo (PBO) | Clavulanic Acid (CLAV) Concentrations Following CLAV 250mg and CLAV 500mg Doses | 0.506 mg/L |
| CLAV 250mg | Clavulanic Acid (CLAV) Concentrations Following CLAV 250mg and CLAV 500mg Doses | 0.394 mg/L |
| CLAV 500mg | Clavulanic Acid (CLAV) Concentrations Following CLAV 250mg and CLAV 500mg Doses | 1.912 mg/L |
Secondary
Difference in CLAV Concentrations Between the 250mg and 500mg CLAV Doses
The CLAV concentration after ingestion of 250mg CLAV minus the CLAV PK level after the 500 mg dose is reported at 40min and 70 min after ingestion
Time frame: 3 days (Day 2, 3, 4)
Population: 10 subjects were randomized and received 250mg and 500mg on different days based on their randomization. One subject's samples were unusable. A second subject vomited after each dose (250mg and 500mg), had nondetectable levels and was excluded in the calculation. This analysis is based on 8 subjects.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Day 1 - IV Cocaine Only | Difference in CLAV Concentrations Between the 250mg and 500mg CLAV Doses | 0.227 mg/L |
| Placebo (PBO) | Difference in CLAV Concentrations Between the 250mg and 500mg CLAV Doses | 0.331 mg/L |
p-value: 0.69Wilcoxon (Mann-Whitney)
p-value: 0.46Wilcoxon (Mann-Whitney)
Secondary
Pharmacokinetic (PK) Parameter of Cocaine-concentration
Cocaine concentrations are reported at 10 min and 30 minutes after cocaine infusion (70 and 90 minutes after administration of placebo (PBO), CLAV 250mg or CLAV 500mg).
Time frame: 3 Days (Study Days 2, 3, 4)
Population: All 10 participants received PBO, CLAV 250mg or 500mg over 3 days in different order according to randomization. One participant is not included in the analysis due to inadequate samples obtained.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Day 1 - IV Cocaine Only | Pharmacokinetic (PK) Parameter of Cocaine-concentration | 0.355 mg/L | Standard Deviation 0.111 |
| Placebo (PBO) | Pharmacokinetic (PK) Parameter of Cocaine-concentration | 0.240 mg/L | Standard Deviation 0.068 |
| CLAV 250mg | Pharmacokinetic (PK) Parameter of Cocaine-concentration | 0.372 mg/L | Standard Deviation 0.094 |
| CLAV 500mg | Pharmacokinetic (PK) Parameter of Cocaine-concentration | 0.215 mg/L | Standard Deviation 0.046 |
| Day 5--CLAV 750mg | Pharmacokinetic (PK) Parameter of Cocaine-concentration | 0.344 mg/L | Standard Deviation 0.086 |
| Day 10--Follow up | Pharmacokinetic (PK) Parameter of Cocaine-concentration | 0.209 mg/L | Standard Deviation 0.049 |
Secondary
Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid
Pupil Diameter (mm) was measured 10 minutes pre-infusion and 10, 15, 30 and 45 min after cocaine infusion. Cocaine infusion was done 1 hour following ingestion of placebo (day 2), CLAV 250 mg (day3), or CLAV 500 mg (day 4). Results are reported as median pupil diameter (mm) with interquartile range at different time points relative to the cocaine infusion as noted.
Time frame: 10 minutes pre-infusion and 10, 15, 30 and 45 min after cocaine infusion on Study Days 2, 3, and 4
Population: 10 subjects receiving IV cocaine infusion were randomized to receive either PBO, CLAV 250mg or CLAV 500mg on days 2, 3,and 4 depending on randomization
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Day 1 - IV Cocaine Only | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 30 min post-infusion | 3.6 mm |
| Day 1 - IV Cocaine Only | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 15 min post-infusion | 3.55 mm |
| Day 1 - IV Cocaine Only | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | -10 min pre-infusion | 3.1 mm |
| Day 1 - IV Cocaine Only | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 10 min post-infusion | 3.55 mm |
| Day 1 - IV Cocaine Only | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 45 min post-infusion | 3.4 mm |
| Placebo (PBO) | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 15 min post-infusion | 3.40 mm |
| Placebo (PBO) | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | -10 min pre-infusion | 3.10 mm |
| Placebo (PBO) | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 10 min post-infusion | 3.70 mm |
| Placebo (PBO) | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 30 min post-infusion | 3.30 mm |
| Placebo (PBO) | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 45 min post-infusion | 3.10 mm |
| CLAV 250mg | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 45 min post-infusion | 3.10 mm |
| CLAV 250mg | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 30 min post-infusion | 3.35 mm |
| CLAV 250mg | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | -10 min pre-infusion | 3.20 mm |
| CLAV 250mg | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 15 min post-infusion | 3.50 mm |
| CLAV 250mg | Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid | 10 min post-infusion | 3.90 mm |