PHASE IIA: Trial of a Novel Ondansetron Formulation (OND-PR002) and Immediate-Release Methylphenidate (Ritalin®)(OND003IND)

NCT01377662 | Completed Phase 2

• 2 other identifiers: Pro000309211RC2DA028905-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

The main purpose of this study is to determine the outcome of a drug combination treatment on detoxified and stabilized methamphetamine (METH) and/or cocaine (COC) dependent users. The combination regimen consists of oral administration of a generic immediate-release methylphenidate (MPh-IR) formulation (e.g., Ritalin®) and a novel delayed, pulsatile-release formulation of the antiemetic ondansetron (Ond-PR002). Various psychological assessment tools and functional magnetic resonance imaging (fMRI) will be used to assess the treatment outcome. In addition to the treatment outcome measures, we will determine whether the 14-day, once-a-day treatment leads to significant changes in the pharmacokinetic/pharmacodynamic (PK/PD), safety and tolerability parameters of MPh-IR and/or Ond-PR002 formulations and drug-drug interactions between the two drugs.

Conditions

Methamphetamine Dependence; Cocaine Dependence

Outcome Measures

Primary Outcomes (1)

• Efficacy of combined Ond-PR002 and MPh-IR treatment

  Efficacy of combined Ond-PR002 and MPh-IR treatment in reducing the Visual Analogue Scale (VAS), Cocaine Selective Severity Assessment (CSSA) and Amphetamine Cessation Symptom Assessment (ACSA) craving scores in abstinent METH/COC abusers. Changes in cue-reactivity and inhibitory control deficits will be also assessed using functional magnetic resonance imaging (fMRI).

  15 days

Secondary Outcomes (4)

• Safety of combined MPh-IR + Ond-PR002 treatment

  15 days

• Changes in the PK parameters of Ond-PR002 PK after 14-day treatment

  15 days

• Changes in the PK parameters of MPh-IR PK after 14-day treatment

  15 days

• Tolerability of combined MPh-IR + Ond-PR002 treatment

  15 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Other: Placebo: Two dextrose capsules for Ond-PR002 and MPh-IR

OND-PR002 and MPh-IR

EXPERIMENTAL

Drug: OND-PR002 and MPh-IR

Interventions

OND-PR002 and MPh-IR DRUG

Drug: OND-PR002 Single daily oral doses of 8 mg Ond-PR002 Drug: MPh-IR Single daily oral doses of 20 mg MPh-IR

Also known as: Ondanasetron, Zofran®, Methylphenidate, Ritalin®

OND-PR002 and MPh-IR

Placebo: Two dextrose capsules for Ond-PR002 and MPh-IR OTHER

Single daily oral doses

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must give written informed consent.
• Detoxified METH/COC-dependent male and/or female subjects between 18 and 45.
• Females with Body Mass Index (BMI) of 18-36 kg/m2. Males with BMI of 20-36 kg/m2.
• Subjects in good health determined by screening examination.
• Subject must have adequate veins for intravenous site.
• Subjects must be mentally stable for minimum of 3 months.
• Non-clinically significant hematology clinical laboratory results.
• Subjects must have hematocrit of greater than or equal to 33%.
• Non-clinically significant screening 12-lead ECG and QT interval (time for ventricular depolarization and repolarization to occur) corrected by Fridericia formula (QTcF) of \< 440 msec for male and \< 460 msec for females.
• Subjects must be right-handed (control for handed-related differences) in lateralized patterns of brain function.
• Ability to identify visual cues during fMRI.
• Subjects' VAS score must be above 20.

You may not qualify if:

• Subjects who consume more than 28 units of alcohol per week.
• Subjects who test positive for drugs of abuse or alcohol.
• Current use of nicotine replacement therapy or other smoking cessation treatment.
• Use of other investigational drugs within 30 days, or at least 5 half-lives of a study medication prior to enrollment.
• Subjects being treated with other psychotropic drug will be excluded based on PI's clinical judgment and potential drug-drug adverse reactions with study drugs.
• Subjects on prescribed, over-the-counter (OTC) or nutraceutical drugs that may influence the PK, safety or efficacy profiles of MPh-IR and/or Ond-PR002 will be excluded, or receive a washout prior to study enrollment. Subjects on drugs or substances known to be strong inhibitors or strong inducers of CYP 3A4/5 enzymes (enzymes involved in the metabolism of xenobiotics) or P-glycoprotein (P-gp) will be excluded in a similar manner.
• Subjects with heart disease or uncontrolled high blood pressure.
• Donation of any blood or plasma in the last month, or donation of \>500mL of blood within the 3 months preceding study drug administration.
• History of serious adverse reaction or allergies to any drug or any other products used in the study.
• Allergies or intolerance to any of the products used in this study.
• Subjects who have allergies to pork-derived medications or those that contain pork-derived products.
• Inability to give informed consent or high likelihood of being unable to complete the necessary confinement.
• Subjects deemed inappropriate for this study by the Principal Investigator.
• Subjects with a documented brain abnormality, history of unexplained loss of consciousness, seizures, history of unexplained syncope, or history of transient ischemic attack or stroke within the past 6 months.
• History of concurrent illness that required hospitalization within 14 days prior to Day 1 or a clinically significant illness within 4 weeks prior to Day 1.

Sponsors & Collaborators

• Tong Lee: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (3)

Duke Addictions Clinic

Durham, North Carolina, 27705, United States

Location

Duke Clinical Research Unit

Durham, North Carolina, 27710, United States

Location

SouthLight

Raleigh, North Carolina, 27610, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Ondansetron; Methylphenidate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines

Study Officials

• Robert J Noveck, MD,PhD

  Duke Clinical Research Unit

  PRINCIPAL INVESTIGATOR

• Ashwin A Patkar, MD

  Psychiatry and Behavioral Sciences

  PRINCIPAL INVESTIGATOR

• Tong Lee, MD, PhD

  Associate Professor Psychiatry and Behavorial Science, Duke University Medical Center

  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: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor Psychiatry and Behavorial Science

Study Record Dates

• First Submitted: June 12, 2011
• First Posted: June 21, 2011
• Study Start: August 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: October 7, 2014

Record last verified: 2014-09

Locations

US (3)