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

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Tong Lee, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01377662
First received: June 12, 2011
Last updated: December 31, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Methamphetamine Dependence
Cocaine Dependence
Drug: OND-PR002 and MPh-IR
Other: Placebo: Two dextrose capsules for Ond-PR002 and MPh-IR
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: PHASE IIA: Randomized, Double Blind, Placebo Controlled, Single Center Clinical Trial of a Combination of a Novel Ondansetron Formulation (OND-PR002) and Immediate-Release Methylphenidate (Ritalin®)

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Efficacy of combined Ond-PR002 and MPh-IR treatment [ Time Frame: 15 days ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Safety of combined MPh-IR + Ond-PR002 treatment [ Time Frame: 15 days ] [ Designated as safety issue: Yes ]
    Number of subjects with clinically significant changes in vital signs, electrocardiogram (ECG), hematology or chemistry panel measurements and number of subjects with self-reported or observed adverse events or serious adverse events will be recorded.

  • Changes in the PK parameters of Ond-PR002 PK after 14-day treatment [ Time Frame: 15 days ] [ Designated as safety issue: No ]
    Standard PK parameters of Ond-PR002 (e.g., maximum serum concentrations, time to reach max. concentration, apparent volume of distribution, etc.) will be calculated based on the serum drug concentrations, and statistical differences between Day 1 and Day 14 will be determined.

  • Changes in the PK parameters of MPh-IR PK after 14-day treatment [ Time Frame: 15 days ] [ Designated as safety issue: No ]
    Standard PK parameters of MPh-IR on Day 1 and Day 14 will be calculated and statistically compared as described for Ond-PR002.

  • Tolerability of combined MPh-IR + Ond-PR002 treatment [ Time Frame: 15 days ] [ Designated as safety issue: Yes ]
    Number of subjects with clinically significant changes in vital signs, electrocardiogram (ECG), hematology or chemistry panel measurements and number of subjects with self-reported or observed adverse events or serious adverse events will be recorded.


Enrollment: 30
Study Start Date: August 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Other: Placebo: Two dextrose capsules for Ond-PR002 and MPh-IR
Single daily oral doses
Other Name: Placebo
Experimental: OND-PR002 and MPh-IR Drug: OND-PR002 and MPh-IR

Drug: OND-PR002

Single daily oral doses of 8 mg Ond-PR002

Drug: MPh-IR

Single daily oral doses of 20 mg MPh-IR

Other Names:
  • Ondanasetron
  • Zofran®
  • Methylphenidate
  • Ritalin®

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • History of clinically significant cardiovascular illness within the past 6 months.
  • History of clinically significant hepatic, renal, pulmonary, metabolic, endocrine, infectious, gastrointestinal, hematologic, oncologic, retinopathy, or other medical disorders.
  • History of unstable psychiatric illness requiring hospitalization within previous 6 months.
  • Subjects with history of glaucoma, color blindness or other uncorrected vision problem.
  • Subjects with QTcF interval duration greater than or equal to 440 msec (males) or greater than or equal to 460 msec (females) obtained from the 12-lead ECG recorder's measurements on the screening ECG.
  • Individuals with a major condition that would make fMRI participation unsafe or uncomfortable.
  • Females who are pregnant, breast-feeding or plan on becoming pregnant.
  • Subjects who have a hematocrit < 33% or hemoglobin < 12.0 g/dL.
  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: NCT01377662

Locations
United States, North Carolina
Duke Clinical Research Unit
Durham, North Carolina, United States, 27710
Duke Addictions Clinic
Durham, North Carolina, United States, 27705
SouthLight
Raleigh, North Carolina, United States, 27610
Sponsors and Collaborators
Tong Lee
Investigators
Principal Investigator: 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
  More Information

No publications provided

Responsible Party: Tong Lee, Associate Professor Psychiatry and Behavorial Science, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01377662     History of Changes
Other Study ID Numbers: Pro00030921, 1RC2DA028905-01
Study First Received: June 12, 2011
Last Updated: December 31, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Methylphenidate
Ondansetron
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Antipruritics
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents

ClinicalTrials.gov processed this record on October 01, 2014