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A Randomized, 4-sequence, 2-period, Double-blind, Placebo Controlled Study With a DSM-IV-TR Diagnosis of Cocaine Abuse (RBP-8000)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Reckitt Benckiser Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01846481
First received: May 1, 2013
Last updated: September 9, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Opioid Dependence
Opioid Related Disorders
Cocaine Dependence
Drug: RBP-8000
Drug: Placebo
Drug: Cocaine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Reckitt Benckiser Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Maximum plasma concentration (Cmax) of Cocaine, (-)Ecgonine methyl ester and RBP-8000 [ Time Frame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion ] [ Designated as safety issue: No ]
  • Time to Maximum Plasma Concentration (Tmax) of Cocaine, (-)Ecgonine methyl ester and RBP-8000 [ Time Frame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) of Cocaine, (-)Ecgonine methyl ester and RBP-8000 [ Time Frame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion ] [ Designated as safety issue: No ]
  • Elimination half-life (t1/2) of Cocaine, (-)Ecgonine methyl ester and RBP-8000 [ Time Frame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to theoretical infinity (AUC0-inf) of Cocaine, (-)Ecgonine methyl ester and RBP-8000 [ Time Frame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion ] [ Designated as safety issue: No ]
  • Distribution half-life (t1/2α) of Cocaine [ Time Frame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion ] [ Designated as safety issue: No ]
  • Clearance (CL) of Cocaine, (-)Ecgonine methyl ester and RBP-8000 [ Time Frame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion ] [ Designated as safety issue: No ]
  • Volume of distribution (Vd) of Cocaine, (-)Ecgonine methyl ester and RBP-8000 [ Time Frame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion ] [ Designated as safety issue: No ]
  • Elimination rate constant (λz) of Cocaine, (-)Ecgonine methyl ester and RBP-8000 [ Time Frame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion ] [ Designated as safety issue: No ]
  • Mean residence time (MRT) of Cocaine, (-)Ecgonine methyl ester and RBP-8000 [ Time Frame: 21 samples from pre-dose of cocaine up to 731 minutes after start of cocaine infusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Behavioral effects - as Measured by the Participant Using the Brief Substance Craving Scale [ Time Frame: Post dosing 30 min,1,0, 2.0, 3.0, 4.0, 7.0, 8.0, 12.0,24.0 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 28
Study Start Date: April 2013
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RBP-8000 100mg/Placebo

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
RBP-8000 administered in the vein at either the 100 or 200 mg level on either study day 3 or 6. There is a 72-hour washout between Days 3 and 6
Other Name: T172R/G173G cocaine esterase
Drug: Placebo
IV infusion of Placebo administered 1 minute after cocaine infusion on either day 3 or 6.
Drug: Cocaine
50 mg intravenous (IV) dose of cocaine administered over 10 minutes on Days 1, 3 and 6.
Other Name: Benzoylmethylecgonine
Experimental: Placebo/RBP-8000 100mg

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
RBP-8000 administered in the vein at either the 100 or 200 mg level on either study day 3 or 6. There is a 72-hour washout between Days 3 and 6
Other Name: T172R/G173G cocaine esterase
Drug: Placebo
IV infusion of Placebo administered 1 minute after cocaine infusion on either day 3 or 6.
Drug: Cocaine
50 mg intravenous (IV) dose of cocaine administered over 10 minutes on Days 1, 3 and 6.
Other Name: Benzoylmethylecgonine
Experimental: RBP-8000 200mg/Placebo

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: RBP-8000
RBP-8000 administered in the vein at either the 100 or 200 mg level on either study day 3 or 6. There is a 72-hour washout between Days 3 and 6
Other Name: T172R/G173G cocaine esterase
Drug: Placebo
IV infusion of Placebo administered 1 minute after cocaine infusion on either day 3 or 6.
Drug: Cocaine
50 mg intravenous (IV) dose of cocaine administered over 10 minutes on Days 1, 3 and 6.
Other Name: Benzoylmethylecgonine
Experimental: Placebo/RBP-8000 200mg

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: RBP-8000
RBP-8000 administered in the vein at either the 100 or 200 mg level on either study day 3 or 6. There is a 72-hour washout between Days 3 and 6
Other Name: T172R/G173G cocaine esterase
Drug: Placebo
IV infusion of Placebo administered 1 minute after cocaine infusion on either day 3 or 6.
Drug: Cocaine
50 mg intravenous (IV) dose of cocaine administered over 10 minutes on Days 1, 3 and 6.
Other Name: Benzoylmethylecgonine

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

Ages Eligible for Study:   21 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01846481

Locations
United States, Kansas
Vince and Associates Clinical Research
Overland Park,, Kansas, United States, 66212
Sponsors and Collaborators
Reckitt Benckiser Pharmaceuticals Inc.
Investigators
Principal Investigator: Bradley D Vince, DO Vince and Associates Clinical Research
  More Information

No publications provided

Responsible Party: Reckitt Benckiser Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01846481     History of Changes
Other Study ID Numbers: RB-US-13-0004
Study First Received: May 1, 2013
Last Updated: September 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Reckitt Benckiser Pharmaceuticals Inc.:
Cocaine

Additional relevant MeSH terms:
Opioid-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders
Cocaine
Anesthetics
Anesthetics, Local
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on February 27, 2015