A Randomized, 4-sequence, 2-period, Double-blind, Placebo Controlled Study With a DSM-IV-TR Diagnosis of Cocaine Abuse

NCT01846481 | Completed Phase 2

• 1 other identifier: RB-US-13-0004
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid Dependence; Opioid Related Disorders; Cocaine Dependence

Keywords

Cocaine

Outcome Measures

Primary Outcomes (10)

• Maximum plasma concentration (Cmax) of Cocaine, (-)Ecgonine methyl ester and RBP-8000

  21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion

• Time to Maximum Plasma Concentration (Tmax) of Cocaine, (-)Ecgonine methyl ester and RBP-8000

  21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion

• Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) of Cocaine, (-)Ecgonine methyl ester and RBP-8000

  21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion

• Elimination half-life (t1/2) of Cocaine, (-)Ecgonine methyl ester and RBP-8000

  21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion

• Area under the plasma concentration-time curve from time 0 to theoretical infinity (AUC0-inf) of Cocaine, (-)Ecgonine methyl ester and RBP-8000

  21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion

• Distribution half-life (t1/2α) of Cocaine

  21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion

• Clearance (CL) of Cocaine, (-)Ecgonine methyl ester and RBP-8000

  21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion

• Volume of distribution (Vd) of Cocaine, (-)Ecgonine methyl ester and RBP-8000

  21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion

• Elimination rate constant (λz) of Cocaine, (-)Ecgonine methyl ester and RBP-8000

  21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion

• Mean residence time (MRT) of Cocaine, (-)Ecgonine methyl ester and RBP-8000

  21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion

Secondary Outcomes (1)

• Behavioral effects - as Measured by the Participant Using the Brief Substance Craving Scale

  Post dosing 30 min,1,0, 2.0, 3.0, 4.0, 7.0, 8.0, 12.0,24.0 hours

Study Arms (4)

RBP-8000 100mg/Placebo

EXPERIMENTAL

Day 1: 50mg intravenous infusion of cocaine Day 3: 50mg intravenous infusion of cocaine followed by a 100mg intravenous infusion of RBP-8000 Day 6: 50mg intravenous infusion of cocaine followed by an intravenous infusion of placebo

Drug: RBP-8000 100 mg; Drug: Placebo; Drug: Cocaine

Placebo/RBP-8000 100mg

EXPERIMENTAL

Day 1: 50mg intravenous infusion of cocaine Day 3: 50mg intravenous infusion of cocaine followed by an intravenous infusion of placebo Day 6: 50mg intravenous infusion of cocaine followed by a 100mg intravenous infusion of RBP-8000

Drug: RBP-8000 100 mg; Drug: Placebo; Drug: Cocaine

RBP-8000 200mg/Placebo

EXPERIMENTAL

Day 1: 50mg intravenous infusion of cocaine Day 3: 50mg intravenous infusion of cocaine followed by a 200mg intravenous infusion of RBP-8000 Day 6: 50mg intravenous infusion of cocaine followed by an intravenous infusion of placebo

Drug: Placebo; Drug: Cocaine; Drug: RBP-8000 200 mg

Placebo/RBP-8000 200mg

EXPERIMENTAL

Day 1: 50mg intravenous infusion of cocaine Day 3: 50mg intravenous infusion of cocaine followed by an intravenous infusion of placebo Day 6: 50mg intravenous infusion of cocaine followed by a 200mg intravenous infusion of RBP-8000

Drug: Placebo; Drug: Cocaine; Drug: RBP-8000 200 mg

Interventions

RBP-8000 100 mg DRUG

RBP-8000 100 mg administered in the vein on either study day 3 or 6. There is a 72-hour washout between Days 3 and 6

Also known as: T172R/G173G cocaine esterase

Placebo/RBP-8000 100mg; RBP-8000 100mg/Placebo

Placebo DRUG

IV infusion of Placebo administered 1 minute after cocaine infusion on either day 3 or 6.

Placebo/RBP-8000 100mg; Placebo/RBP-8000 200mg; RBP-8000 100mg/Placebo; RBP-8000 200mg/Placebo

Cocaine DRUG

50 mg intravenous (IV) dose of cocaine administered over 10 minutes on Days 1, 3 and 6.

Also known as: Benzoylmethylecgonine

Placebo/RBP-8000 100mg; Placebo/RBP-8000 200mg; RBP-8000 100mg/Placebo; RBP-8000 200mg/Placebo

RBP-8000 200 mg DRUG

RBP-8000 200 mg administered in the vein on either study day 3 or 6. There is a 72-hour washout between Days 3 and 6

Also known as: T172R/G173G cocaine esterase

Placebo/RBP-8000 200mg; RBP-8000 200mg/Placebo

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indivior Inc.: lead

Study Sites (1)

Vince and Associates Clinical Research

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Cocaine-Related Disorders

Interventions

RBP-8000; Cocaine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Bradley D Vince, DO

  Vince and Associates Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2013
• First Posted: May 3, 2013
• Study Start: April 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: September 23, 2016

Record last verified: 2016-09

Locations

US (1)