Safety, Tolerability, and Pharmacokinetics of Single, Escalating Oral Doses of RTI-336 in Healthy, Male Subjects

NCT00808119 | Completed Phase 1 DMC

• 1 other identifier: RTI-336-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is the first study to be conducted in humans for RTI-336, a new chemical entity, with evaluations focusing on the safety, tolerability, and pharmacokinetics of RTI-336 following administration of single, oral doses. RTI-336 is a novel dopamine transporter inhibitor of the 3-phenyltropane class, and is currently being developed by RTI International as a potential pharmacotherapy to treat cocaine dependence. Data from this study will be used to plan and define dose ranges for subsequent studies.

Conditions

Cocaine Dependence

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of RTI-336; clinical signs and symptoms, adverse events (AEs), vital signs, electrocardiographic (ECG) parameters, clinical laboratory test results

  Days 0 (Baseline), 1-3, and 8

Secondary Outcomes (1)

• Pharmacokinetic parameters of RTI-336 and metabolites

  0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 30, 36, and 48 hours after dosing

Interventions

RTI-336 (CTDP 31862) DRUG

The RTI-336 drug product is formulated as hard, white, gelatin capsules. The dosage levels are 0.3, 1.0, and 3.0 mg (Cohort 1) and 6.0, 12.0, and 20.0 mg (Cohort 2). Subjects will receive a single dose of the study drug on study day 1.

Eligibility Criteria

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

You may qualify if:

• Subject provides signed and dated, written informed consent prior to any study-specific procedures being performed, including washout of any medications and compliance with food/beverage restrictions.
• Subject is a healthy adult male, 18-50 years of age, inclusive, at the time of consent, with body weight greater than or equal to 50 kg and a body mass index (BMI) in the range of 18-30 kg/m2, where BMI = weight (kg)/\[height (m)\]2.
• Subject has a negative pre-study urine drug screen and no history of cocaine use or use of other illicit drugs or substances of abuse within 12 months of the screening visit. Drugs or substances analyzed in the urine screen include cocaine, amphetamines, barbiturates, opioids, cannabinoids, benzodiazepines, phencyclidine, alcohol, and cotinine.
• Subject is a non-tobacco user or a prior user who quit using tobacco at least 90 days prior to screening.
• Subject has no history of any cardiovascular disease and has a normal ECG and serum troponin at screening.
• Subject is negative for hepatitis C antibodies, hepatitis B surface antigen and human immunodeficiency virus (HIV) at screening.
• Subject is in good general health, in the opinion of the Investigator, and as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory tests at screening. Additionally, the subject's clinical laboratory test results must meet the following criteria: Within normal limits for sodium, protein, total WBC, hematocrit, hemoglobin, reticulocyte count, platelets, AST (SGOT), ALT (SGPT), GGT, and troponin I. Within upper limit of normal and no more than 10% below lower limit: BUN creatinine, bilirubin, total alkaline phosphatase, creatine kinase, and LDH. Within 10% of normal range and considered to be not clinically significant:calcium chloride, phosphorus, albumin, globulin, cholesterol, triglycerides, and RBC. No clinically significant abnormalities: glucose, potassium, white blood cell differential, red blood cell indices, uric acid, and urinalysis.
• Subject is willing to use barrier contraception with spermicide during sexual intercourse while enrolled in this study and for at least 30 days after the last dose of study drug.
• Subject is willing and able to comply with study instructions and restrictions, and is available to complete the study assessments as required by the protocol.
• Subjects is fluent in either English or Spanish

You may not qualify if:

• A subject will be excluded from participation in the study if any of the following criteria applies:
• Subject self-reports a history of chronic illicit drug use or chronic use of other substances of abuse.
• Subject has a positive urine drug/alcohol/cotinine test at screening or prior to dosing in any dose period.
• Subject has a history or evidence of hepatic, gastrointestinal, renal, respiratory, ophthalmic, cardiovascular, hematologic, endocrine/metabolic, neurologic, immunologic, oncologic or psychiatric illness or significant abnormalities.
• Subject has a history of and/or current major depression, psychotic symptoms, or anxiety disorder(s) based on the Major Depressive Episode, Psychotic, and Anxiety Disorder modules of the Structured Clinical Interview for DSM Disorders (details documented in study protocol).
• Subject has a family history of psychiatric illness (psychosis, depression, anxiety disorders).
• Subject has an abnormal ECG at screening or prior to dosing in each dose period. Premature atrial contraction or premature ventricular contraction is considered abnormal, as are bundle branch blocks, second or third degree heart block, or any arrhythmia other than respiratory sinus arrhythmia. Abnormalities also include but are not limited to the following: Heart Rate \< 45 or \> 100 bpm; PR interval \< 120 or \> 220 msec; QRS duration \< 70 or \> 120 msec; and QTC interval (Bazett) \> 460 msec.
• Subject has a history or family history of QT prolongation, arrhythmia, or uncontrolled hypertension.
• Subject has a history of seizure, head injury, neurosurgery or brain trauma, or a family history of non-traumatic seizure.
• Subject is positive for hepatitis C antibodies at screening, or hepatitis B surface antigen or HIV at screening.
• Subject has an infection of any type or clinically significant abnormality identified by the screening medical or laboratory evaluations.
• Subject has a history of using tobacco-containing products within 90 days of screening.
• Subject has a history of significant alcohol consumption, defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units, with 1 unit equivalent to a half-pint (220 mL) of beer, or 1 measure of spirits, or 1 glass (125 mL) of wine.
• Subject has consumed grapefruit or grapefruit-containing, or poppy-seed or quinine-containing substances within 14 days of the first dose period.
• Subject has used any other drug, including prescription or non-prescription medications and herbal supplements, within 30 days prior to the first dose of study drug, with the exception of acetaminophen, which may be taken up to 24 hours prior to dosing in each dose period.

Sponsors & Collaborators

• RTI International: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Comprehensive Phase One

Miramar, Florida, 33025, United States

Location

Related Publications (1)

• Carroll FI, Kosten TR, Buda JJ, Wang L, Walters BB. A Double-Blind, Placebo-Controlled Trial Demonstrating the Safety, Tolerability, and Pharmacokinetics of Single, Escalating Oral Doses of RTI-336. Front Pharmacol. 2018 Jul 10;9:712. doi: 10.3389/fphar.2018.00712. eCollection 2018.

  PMID: 30042675 DERIVED

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

3beta-(4-chlorophenyl) tropane-2beta-(3-(4'-methylphenyl) isoxazol-5-yl) hydrochloride

Condition Hierarchy (Ancestors)

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

Study Officials

• William A. Gerson, DO, CPI

  Comprehensive Phase One

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 12, 2008
• First Posted: December 15, 2008
• Study Start: October 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: July 21, 2009

Record last verified: 2009-07

Locations

US (1)