Pharmacokinetic and Safety Evaluation of L-tetrahydropalmatine (l-THP) With Cocaine Exposure in People With a History of Cocaine Use

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Maryland
Sponsor:
Collaborator:
Information provided by (Responsible Party):
MPRC, University of Maryland
ClinicalTrials.gov Identifier:
NCT01631383
First received: June 18, 2012
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

This study will test the safety and pharmacokinetic profile of l-THP with cocaine exposure in people who have a history of cocaine use. The subject will be admitted to the Brief Stay Unit (BSU), an inpatient facility at the Maryland Psychiatric Research Center, used for short term drug abuse or clinical trial studies. The participant will stay for 4 nights and 5 days. He/she will be randomized to either placebo or l-THP for three days. On the morning of Day 4, the subject will receive one cocaine dose (40 mg intranasal) and have testing for pharmacokinetic parameters for the following 10 hours. The subject will stay over one more night and will be discharged the following day. Approximately 40 subjects will be randomized to enroll the target sample of 30 (N=15 placebo, N=15 l-THP). In summary, each subject will come for a screening visit(s), then a 5-day, 4-night stay on a secure research unit. After cocaine administration day, the participant will stay overnight for one more day of observation and to permit substantial l-THP elimination from the body. The following morning we will get one additional blood specimen for l-THP (Day 5 at 24 hours after last dose (7:30 am); then the participant will be discharged. A visit with blood collection on Day 6 at 55 hours after last dose (2:30 pm) will be scheduled. A final follow-up visit will be scheduled 4-7 days after unit discharge to ensure no persisting side effects.


Condition Intervention Phase
Cocaine Use
Drug: l-THP (l-tetrahydropalmatine)
Drug: Placebo
Phase 1

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: Pharmacokinetic and Safety Evaluation of L-tetrahydropalmatine (l-THP) With Cocaine Exposure in People With a History of Cocaine Use

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Peak heart rate after cocaine administration during treatment with l-THP or placebo. [ Time Frame: -10 (min), 5, 20, 35, 50, 65, 80, 95, 2.5 (hr), 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9 10 hr ] [ Designated as safety issue: Yes ]
    Comparing the peak changes between the two groups accounting for the specified tolerance margin

  • Peak blood pressure after cocaine administration during treatment with l-THP or placebo [ Time Frame: -10 (min), 5, 20, 35, 50, 65, 80, 95, 2.5 (hr), 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9 10 hr ] [ Designated as safety issue: Yes ]
    Comparing the peak changes between the two groups accounting for the specified tolerance margin

  • Peak cocaine plasma concentration after acute cocaine dose during treatment with l-THP [ Time Frame: 0,1,20,30,40,50,60,70,80,90, 100, 110 (min), 2 (hr), 2.5, 3, 3.5, 4, 5, 6 hr ] [ Designated as safety issue: Yes ]
    Cmax and AUC will be compared between the two groups


Secondary Outcome Measures:
  • Reported side effects of l-THP vs placebo during 3 day dosing [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
    Standard side effects will be measured using Side Effect Checklist before and after 3 Days of l-THP or placebo

  • Safety (laboratory measures) of l-THP vs. placebo during 3 day dosing [ Time Frame: 3 Days ] [ Designated as safety issue: Yes ]
    We will examine routine CBC and Chemistry panel for changes in labatory measures During 3 days of dosing

  • Extrapyramidal Side effects of l-THP vs. placebo during 3 days of dosing [ Time Frame: 3 Days ] [ Designated as safety issue: Yes ]
    Simpson Angus Scale and Barnes Akathisia Scale will be compared for extrapyramidal Side effects between groups

  • Psychological Side Effects of l-THP vs. placebo during 3 days of dosing [ Time Frame: 3 Days ] [ Designated as safety issue: Yes ]
    Symptom Checklist-90 will be compared for psychological side effects between groups

  • Craving for cocaine during treatment with l-THP or placebo [ Time Frame: 3Days ] [ Designated as safety issue: No ]
    Craving for cocaine will be compared using the cocaine craving questionnaire and The cocaine visual analog scales between groups


Estimated Enrollment: 40
Study Start Date: October 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Subjects will arrive the first day (Day 1) for admission and morning l-THP dosing. The l-THP will be dosed as one capsule 30 mg twice daily (matching placebo or l-THP) (total 60 mg daily). Participants will receive 7 total l-THP doses: two doses on Day 1 (morning and evening), two doses on Day 2 (morning and evening), 2 doses on Day 3 (morning and evening) and one dose the morning of Day 4 (cocaine administration day).
Active Comparator: l-THP Drug: l-THP (l-tetrahydropalmatine)
Subjects will arrive the first day (Day 1) for admission and morning l-THP dosing. The l-THP will be dosed as one capsule 30 mg twice daily (matching placebo or l-THP) (total 60 mg daily). Participants will receive 7 total l-THP doses: two doses on Day 1 (morning and evening), two doses on Day 2 (morning and evening), 2 doses on Day 3 (morning and evening) and one dose the morning of Day 4 (cocaine administration day).
Other Name: l-tetrahydropalmatine

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion/Exclusion Criteria:

Inclusion criteria:

  1. men or non-pregnant/non-nursing women between the ages of 18 and 50 years old
  2. self reported history of cocaine use (intranasal, IV or smoked) averaging at least twice monthly for at least one month over the prior year
  3. self- reported use at least one use in the past six months of a cocaine dose equivalent to 40 mg intranasal or 15 mg smoked or intravenous, based on participant's best estimate of weight and/or street price of amount ingested and a
  4. positive urine drug test for cocaine use at least once in past 1 year
  5. HIV seronegative
  6. hepatitis C seronegative
  7. EKG without clinically significant abnormality
  8. normal blood pressure (systolic: 90-140 mmHg; diastolic: 50-90 mmHg) and resting heart rate (60-90 bpm)
  9. within 20% of ideal body weight, based on BJ Devine formula (1974) (men: 50 + 2.3 kg per inch over 5 feet, women: 45.5 + 2.3 kg per inch over 5 feet)
  10. ability to adhere to the study restrictions and examination schedule
  11. Women with reproductive potential must agree to the use of one of the following birth control methods (condom with spermicide, diaphragm, or intrauterine device) during the study and for 2 weeks after study conclusion.

Exclusion criteria:

  1. participation in any investigational drug trial or clinical drug trial within 45 days before study entry
  2. donation or loss of greater than one pint of blood within 60 days of study entry
  3. history of clinically significant adverse reaction or hypersensitivity to any study drug,
  4. inability to communicate or co-operate with the investigators
  5. treatment-seeking for cocaine abuse/dependence
  6. taking any concurrent prescription, over the counter medications, or dietary/nutritional/herbal supplement (such as St. John's wort or grapefruit juice, but not including standard vitamin or mineral supplements) within 14 days prior to initial dosing.
  7. current clinically significant medical problems that might interfere with safe study participation. This includes pheochromocytoma, untreated hyperthyroidism, dehydration, fever, coronary artery disease, uncorrected congenital heart defect, seizures, electrolyte imbalance, uncontrolled diabetes mellitus, porphyria variegate, superventricular tachycardia, atrial fibrillation, cardiomyopathy, uncontrolled hypertension,.
  8. Current Axis I psychiatric disorder (except nicotine dependence, cocaine abuse/dependence, or simple phobia). Nicotine does not alter physiologic response to cocaine (Kouri et al 2001)
  9. Positive for illicit drugs other than cocaine or marijuana on urine drug screen
  10. Score below 10/12 on the Evaluation to Sign Consent (ESC)
  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: NCT01631383

Contacts
Contact: Ann Kearns, BS 410-402-6854 akearns@mprc.umaryland.edu
Contact: Stephanie Feldman, MSW 410-402-6885 sfeldman@mprc.umaryalnd.edu

Locations
United States, Maryland
Maryland Psychiatric Research Center Recruiting
Catonsville, Maryland, United States, 21228
Contact: Ann Kearns, BS    410-402-6854    akearns@mprc.umaryland.edu   
Contact: Stephanie Feldman, MSW    410-402-6885    sfeldman@mprc.umaryland.edu   
Principal Investigator: Deanna L. Kelly, Pharm.D., BCPP         
Principal Investigator: Jia Bei Wang, MD, Ph.D         
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Deanna L. Kelly, Pharm.D., BCPP University of Maryland
  More Information

Additional Information:
No publications provided

Responsible Party: MPRC, Deanna L. Kelly, Pharm.D., BCPP, University of Maryland
ClinicalTrials.gov Identifier: NCT01631383     History of Changes
Other Study ID Numbers: HP-00051290, 1DP1DA031401-01
Study First Received: June 18, 2012
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Maryland:
Cocaine Use

Additional relevant MeSH terms:
Cocaine
Tetrahydropalmatine
Adrenergic Agents
Analgesics
Analgesics, Non-Narcotic
Anesthetics
Anesthetics, Local
Anti-Arrhythmia Agents
Antihypertensive Agents
Antipsychotic Agents
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Dopamine Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses
Tranquilizing Agents
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on October 23, 2014