Cocaine-related Disorder
Conditions
Keywords
Cocaine Use Disorder; cocaine dependence,AFQ056,adult, cocaine use,CUD, drug abuse, drug addiction,
Brief summary
This study assessed whether AFQ056 had a beneficial effect by reducing cocaine use in Cocaine Use Disorder (CUD) patients as assessed by Timeline Follow-Back cocaine self-report.
Detailed description
This was a randomized, subject- and Investigator-blinded, parallel-group, placebo-controlled study in subjects with CUD. The study consisted of a 17-day screening period followed by a 12-day baseline, a 98-day outpatient treatment period (14-day up-titration dose regimen followed by 84-day maintenance dose), and an End of Study evaluation visit approximately 14 days after the last study drug administration. The total duration for each subject in the study was approximately 20 weeks including screening and baseline.
Interventions
DRUGAFQ056
50 mg and 100 mg tablets taken orally
DRUGPlacebo
Matching placebo tablets taken orally BID
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Understand the study procedures and provide written informed consent before any assessment is performed. * Subjects diagnosed with Cocaine Use Disorder according to DSM 5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Ed.). * Must use cocaine through snorting (intranasally) as primary route of administration. * Recent cocaine use confirmed by positive urine screen for 1 or more benzoylecgonine (BE). * Must be seeking treatment for cocaine dependence and have a desire to reduce or cease cocaine use.
Exclusion criteria
* Has current diagnosis of Substance Use Disorder (according to the DSM 5) on alcohol, cannabis or other stimulants, except cocaine. * Meets current or lifetime DSM 5 criteria for schizophrenia or any psychotic disorder, or organic mental disorder. * Have current treatment for Substance Use Disorder (e.g.: disulfiram, acamprosate, methyl phenidate, modafinil, topiramate, immediate release dexamfetamine,or baclofen). * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test * Have a history of any illness, condition, and use of medications that in the opinion of the investigator or designee might confound the results of the study or pose additional risk in administering the investigational agents to the subject or preclude successful completion of the study * Current or/and previous treatment with concomitant medications that are strong or moderate inducers/inhibitors of CYP3A4 (e.g., clarithromycin, ketoconazole, ritonavir, etc.) * History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. * Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). * Score yes on item 4 or item 5 of the Suicidal Ideation section of the CSSRS, if this ideation occurred in the past 6 months, or yes on any item of the Suicidal Behavior section, except for the Non-Suicidal Self-Injurious Behavior (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years. * Controlled hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Cocaine Use Days | Day 1 up to day 98 | The cocaine consumption was recorded once daily (Yes/No) by the subject using the Timeline Follow-Back (TLFB) cocaine assessment tool during the treatment period. For each patient, the proportion of cocaine use days was calculated by dividing the number of days of cocaine use during the treatment period, i.e. 98 days for completers and number of days between Day 1 and day of last dose in case of premature discontinuation of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Positive Urine Measurements of Benzoylecgonine (BE) | Day 1 up to day 98 | Urine samples were analyzed for the presence of cocaine's metabolite benzoylecgonine (BE) which is the main metabolite of cocaine present in urine. Two urine samples were provided per week to provide a quantitative measure. |
| Proportion of Days of Alcohol Consumption | Day 1 up to day 98 | Alcohol consumption was recorded by the subjects using the Timeline Follow-Back (TLFB) alcohol self report. The number of standard drinks were recorded daily. The proportion of days of alcohol consumption during the study treatment period was was compared using an ANCOVA model with treatment as factor and past alcohol consumption as covariate. The past consumption of alcohol was the proportion of alcohol over the 28 days preceding the screening visit, which was assessed retrospectively using the TLFB. |
| AFQ056 Plasma Concentrations | Day 15 (0h, 2h), Day 29 (0, 2h), Day 57 (0h, 2h), Day 98 (0h,2h) | Plasma samples were collected to assess pharmacokinetics (PK) |
Countries
Argentina, Spain, Switzerland
Participant flow
Pre-assignment details
There were 68 patients who received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| AFQ056 Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days | 31 |
| Placebo Matching tablet of placebo taken orally BID | 37 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | AFQ056 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 35.4 years STANDARD_DEVIATION 8.31 | 35.5 years STANDARD_DEVIATION 9.19 | 35.4 years STANDARD_DEVIATION 8.74 |
| Age, Customized 18 - 65 years | 31 Participants | 37 Participants | 68 Participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 31 participants | 36 participants | 67 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 26 Participants | 30 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 37 |
| other Total, other adverse events | 26 / 31 | 30 / 37 |
| serious Total, serious adverse events | 0 / 31 | 1 / 37 |
Outcome results
Primary
Proportion of Cocaine Use Days
The cocaine consumption was recorded once daily (Yes/No) by the subject using the Timeline Follow-Back (TLFB) cocaine assessment tool during the treatment period. For each patient, the proportion of cocaine use days was calculated by dividing the number of days of cocaine use during the treatment period, i.e. 98 days for completers and number of days between Day 1 and day of last dose in case of premature discontinuation of study treatment.
Time frame: Day 1 up to day 98
Population: Pharmacodynamic analysis set (PD): subjects with any available efficacy (PD) data, who received study drug for at least 14 days with no relevant protocol deviation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AFQ056 | Proportion of Cocaine Use Days | 0.122 cocaine use days | Standard Error 0.027 |
| Placebo | Proportion of Cocaine Use Days | 0.209 cocaine use days | Standard Error 0.024 |
p-value: =0.02195% CI: [-0.161, -0.013]ANCOVA
Secondary
AFQ056 Plasma Concentrations
Plasma samples were collected to assess pharmacokinetics (PK)
Time frame: Day 15 (0h, 2h), Day 29 (0, 2h), Day 57 (0h, 2h), Day 98 (0h,2h)
Population: Number of samples available for analysis varied across time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AFQ056 | AFQ056 Plasma Concentrations | Day 15 2 hour | 78.0 ng/mL | Standard Deviation 91.7 |
| AFQ056 | AFQ056 Plasma Concentrations | Day 29 0 hour | 83.5 ng/mL | Standard Deviation 116 |
| AFQ056 | AFQ056 Plasma Concentrations | Day 15 0 hour | 41.2 ng/mL | Standard Deviation 47.4 |
| AFQ056 | AFQ056 Plasma Concentrations | Day 29 2 hour | 148 ng/mL | Standard Deviation 131 |
| AFQ056 | AFQ056 Plasma Concentrations | Day 57 0 hour | 108 ng/mL | Standard Deviation 153 |
| AFQ056 | AFQ056 Plasma Concentrations | Day 57 2 hour | 141 ng/mL | Standard Deviation 153 |
| AFQ056 | AFQ056 Plasma Concentrations | Day 98 0 hour | 89.8 ng/mL | Standard Deviation 148 |
| AFQ056 | AFQ056 Plasma Concentrations | Day 98 2 hour | 116 ng/mL | Standard Deviation 86.1 |
Secondary
Proportion of Days of Alcohol Consumption
Alcohol consumption was recorded by the subjects using the Timeline Follow-Back (TLFB) alcohol self report. The number of standard drinks were recorded daily. The proportion of days of alcohol consumption during the study treatment period was was compared using an ANCOVA model with treatment as factor and past alcohol consumption as covariate. The past consumption of alcohol was the proportion of alcohol over the 28 days preceding the screening visit, which was assessed retrospectively using the TLFB.
Time frame: Day 1 up to day 98
Population: Pharmacodynamic analysis set (PD): subjects with any available efficacy (PD) data, who received study drug for at least 14 days with no relevant protocol deviation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AFQ056 | Proportion of Days of Alcohol Consumption | 0.233 alcohol consumption days | Standard Error 0.03 |
| Placebo | Proportion of Days of Alcohol Consumption | 0.303 alcohol consumption days | Standard Error 0.026 |
p-value: =0.07295% CI: [-0.146, 0.006]ANCOVA
Secondary
Proportion of Positive Urine Measurements of Benzoylecgonine (BE)
Urine samples were analyzed for the presence of cocaine's metabolite benzoylecgonine (BE) which is the main metabolite of cocaine present in urine. Two urine samples were provided per week to provide a quantitative measure.
Time frame: Day 1 up to day 98
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AFQ056 | Proportion of Positive Urine Measurements of Benzoylecgonine (BE) | 0.666 positive urine samples | Standard Error 0.057 |
| Placebo | Proportion of Positive Urine Measurements of Benzoylecgonine (BE) | 0.843 positive urine samples | Standard Error 0.051 |
p-value: =0.02595% CI: [-0.331, -0.023]ANOVA