Clinical trial NCT01846481: A Randomized, 4-sequence, 2-period, Double-blind, Placebo Controlled Study With a DSM-IV-TR Diagnosis of Cocaine Abuse
Official title: A Randomized, Double-blind, Placebo-controlled, Dose of RBP-8000 Following IV Cocaine to Evaluate the Pharmacokinetics Parameters of RBP-8000 and Cocaine and to Assess the Effects of Drug on Cocaine-induced Physiologic and Behavioral Effects in Cocaine Abusing Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid Dependence
Opioid Related Disorders
Cocaine Dependence
Keywords: Cocaine
Lead sponsor: Indivior Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-03
Enrollment: 40
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a randomized, 4-sequence, 2-period, double-blind, placebo controlled study in male and female subjects with an American Psychiatric Association Diagnostic and Statistical Manual DSM-IV-TR diagnosis of cocaine abuse.

Detailed description: There will be a 28-day screening period with eligible subjects remaining resident in the clinic from the evening before Day -1 up and until the morning of Day 9. On the morning of Day 1, a 50 mg intravenous (IV) infusion of cocaine will be administered over 10 minutes to all subjects. If none of the stopping criteria were met and no intervening safety concerns, subjects will be randomized to one of the treatment sequences on Day 3. On dosing days, Day 3 and Day 6, subjects will have fasted at least 8 hours before dosing of cocaine and either RBP-8000 200 mg, RBP-8000 100 mg or matching placebo.

Eligibility criteria: Inclusion Criteria:

* Male and female volunteers aged 21-50 years, inclusive
* Body mass index (BMI)18-32 kg/m\^2 and weight of at least 50 kg
* Not currently seeking treatment for substance abuse or substance dependence
* Subject is healthy, in the opinion of the Principal Investigator other than cocaine abuse; as determined by the absence of clinically significant medical/psychiatric history or findings, particularly cardiovascular or central nervous system (CNS) disease, physical examination, normal renal function, ECG findings, vital signs, and laboratory results at screening
* Males agree to refrain from sperm donations for the entire duration of the study, and for at least 90 days after the last dose of study drug
* Has experience using cocaine by the smoked or IV route at least 6 times in past 12 months and a positive urine drug screen for cocaine prior to study intake (Day -2). Has experience using cocaine by the smoked or IV route in the past 3 months and a positive urine drug screen for cocaine during screening prior to study check-in at the clinic
* Be able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures, prior to the initiation of any protocol-specific procedures
* Meet DSM-IV-TR criteria for current cocaine abuse
* Be able to comply with protocol requirements, rules, and regulations of the study site, and be likely to complete all the study procedures in the opinion of the Principal Investigator

Exclusion Criteria:

* Current or past history of seizure disorder, including alcohol- and/or stimulant-related seizure, febrile seizure, or significant family history of idiopathic seizure disorder. Have any previous clinically significant reaction to cocaine, including loss of consciousness or seizure
* Current alcohol dependence or current drug dependence according to DSM-IV-TR criteria (excluding nicotine and caffeine)
* Clinically significant history of cardiac disease, including cardiovascular and conduction abnormalities or ECG evidence of cardiac abnormalities
* QTcF greater than or equal to 450 for male subjects and 470 for female subjects as measured through a 12-lead ECG
* History of liver disease or current elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) exceeding 3x the upper limit of normal
* Be on probation or parole, and/or have current or pending legal charges with the potential for incarceration that could interfere with the study scheduling
* Women with a positive pregnancy test at screening; or women who are pregnant or lactating or who are seeking to become pregnant
* Women of childbearing potential (who are sexually active with a male) who fail to use medically acceptable contraception methods (e.g., an oral or injectable contraceptive, an approved hormonal implant or topical patch, an intrauterine device, a double barrier method, or barrier plus spermicide). A woman of childbearing potential is defined as any female who is less than 2 years post-menopausal or has not undergone a hysterectomy or surgical sterilization, e.g., bilateral tubal ligation, bilateral ovariectomy (oophorectomy). Females that are post-menopausal will be confirmed as such by the follicle stimulating hormone (FSH) test at initial screening
* Males who do not agree to use barrier contraception and spermicide when engaging in sexual activity with a female of child-bearing potential while on study medication, and for at least 28 days after the last dose of study medication
* History of clinically significant severe allergic or anaphylactic reactions

Primary outcomes:
measure: Maximum plasma concentration (Cmax) of Cocaine, (-)Ecgonine methyl ester and RBP-8000
timeFrame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion
measure: Time to Maximum Plasma Concentration (Tmax) of Cocaine, (-)Ecgonine methyl ester and RBP-8000
timeFrame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion
measure: Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) of Cocaine, (-)Ecgonine methyl ester and RBP-8000
timeFrame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion
measure: Elimination half-life (t1/2) of Cocaine, (-)Ecgonine methyl ester and RBP-8000
timeFrame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion
measure: Area under the plasma concentration-time curve from time 0 to theoretical infinity (AUC0-inf) of Cocaine, (-)Ecgonine methyl ester and RBP-8000
timeFrame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion
measure: Distribution half-life (t1/2α) of Cocaine
timeFrame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion
measure: Clearance (CL) of Cocaine, (-)Ecgonine methyl ester and RBP-8000
timeFrame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion
measure: Volume of distribution (Vd) of Cocaine, (-)Ecgonine methyl ester and RBP-8000
timeFrame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion
measure: Elimination rate constant (λz) of Cocaine, (-)Ecgonine methyl ester and RBP-8000
timeFrame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion
measure: Mean residence time (MRT) of Cocaine, (-)Ecgonine methyl ester and RBP-8000
timeFrame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion
Secondary outcomes:
measure: Behavioral effects - as Measured by the Participant Using the Brief Substance Craving Scale
timeFrame: Post dosing 30 min,1,0, 2.0, 3.0, 4.0, 7.0, 8.0, 12.0,24.0 hours
Other outcomes:
Locations:
city: Overland Park,
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
Study officials:
affiliation: Vince and Associates Clinical Research
name: Bradley D Vince, DO
role: PRINCIPAL_INVESTIGATOR
References: