<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02232789</url>
  </required_header>
  <id_info>
    <org_study_id>IMIMFTCL/MEF/1</org_study_id>
    <nct_id>NCT02232789</nct_id>
  </id_info>
  <brief_title>Abuse Liability and Human Pharmacology of Mephedrone</brief_title>
  <official_title>Abuse Liability and Human Pharmacology of Mephedrone (4-methylmethcathinone,4-MMC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Parc de Salut Mar</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Instituto de Salud Carlos III</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Parc de Salut Mar</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purposes of this study are 1) to evaluate the abuse liability and human pharmacology of&#xD;
      mephedrone after oral administration and 2) to compare the pharmacological effects of&#xD;
      mephedrone with those obtained after administration of oral 3,4-methylenedioxymethamphetamine&#xD;
      (MDMA, ecstasy).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Mephedrone is a new psychoactive substance (NPS). At present, there are no randomized&#xD;
      controlled trials evaluating the effects of mephedrone in humans. The current body of&#xD;
      knowledge regarding the acute effects of mephedrone is based on anecdotal, self-reported&#xD;
      effects (e.g. internet forums), case reports, and emergency room series and fatalities.&#xD;
&#xD;
      The aims of this study are 1) to evaluate the abuse liability and human pharmacology of&#xD;
      mephedrone after oral administration and 2) to compare the pharmacological effects of&#xD;
      mephedrone with those obtained after administration of oral 3,4-methylenedioxymethamphetamine&#xD;
      (MDMA, ecstasy).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in blood pressure</measure>
    <time_frame>From pre-dose (baseline) to 4h post-dose</time_frame>
    <description>Systolic and diastolic blood pressure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in euphoria-good effects</measure>
    <time_frame>From pre-dose (baseline) to 4h post-dose</time_frame>
    <description>Euphoria-good effects effects will be measured using rating scales (visual analogue scales, the Addiction Research Center Inventory and the Evaluation of the Subjective Effects of Substances with Abuse Potential questionnaires). All these instruments include measures of euphoria-good effects and other feelings induced by psychostimulants</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-Time Curve (AUC 0-24h)</measure>
    <time_frame>From baseline (pre-dose, 0h) to 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24h post-dose</time_frame>
    <description>Calculation of AUC of the concentrations of mephedrone and MDMA and its metabolites in blood, urine, oral fluid and sweat.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Serious and Non-Serious Adverse Events</measure>
    <time_frame>7 days after each substance administration</time_frame>
    <description>Collection of adverse effects spontaneously reported by the participants and/or observed by the investigators</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life</measure>
    <time_frame>From baseline to 24h post-dose</time_frame>
    <description>Calculation of elimination hal-life from concentrations of mephedrone, MDMA and its metabolites in plasma-blood, urine, oral fluid and sweat.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in heart rate</measure>
    <time_frame>From pre-dose (baseline) to 4h post-dose</time_frame>
    <description>Measure of heart rate (pulse)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in pupil diameter</measure>
    <time_frame>From pre-dose (baseline) to 4h post-dose</time_frame>
    <description>Measure of pupil diameter and capacity of convergence (esophoria) using a pupillometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in oral temperature</measure>
    <time_frame>From pre-dose (baseline) to 4h post-dose</time_frame>
    <description>Measure of temperature in mouth using automatic thermometer</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Amphetamine-Related Disorders</condition>
  <arm_group>
    <arm_group_label>Mephedrone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mephedrone 200 mg, single dose, oral administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3,4-methylenedioxymethamphetamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>3,4-methylenedioxymethamphetamine (MDMA) 100 mg, single dose, oral administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lactose</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, single dose, oral administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mephedrone</intervention_name>
    <description>Single oral dose mephedrone</description>
    <arm_group_label>Mephedrone</arm_group_label>
    <other_name>4-methylmethcathinone</other_name>
    <other_name>4-MMC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>3,4-methylenedioxymethamphetamine</intervention_name>
    <description>Single oral dose MDMA</description>
    <arm_group_label>3,4-methylenedioxymethamphetamine</arm_group_label>
    <other_name>MDMA</other_name>
    <other_name>Ecstasy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single oal dose placebo</description>
    <arm_group_label>Lactose</arm_group_label>
    <other_name>Non active treatment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Understanding and accepting the study procedures and signing the informed consent.&#xD;
&#xD;
          -  Male adults volunteers (18-45 years old).&#xD;
&#xD;
          -  Clinical history and physical examination demonstrating no organic or psychiatric&#xD;
             disorders.&#xD;
&#xD;
          -  The ECG and general blood and urine laboratory tests performed before the study should&#xD;
             be within normal ranges. Minor or occasional changes from normal ranges are accepted&#xD;
             if, in the investigator's opinion, considering the current state of the art, they are&#xD;
             not clinically significant, are not life-threatening for the subjects and do not&#xD;
             interfere with the product assessment. These changes and their non-relevance will be&#xD;
             justified in writing specifically.&#xD;
&#xD;
          -  Recreational use of amphetamines, ecstasy and hallucinogen derivatives, mephedrone or&#xD;
             other cathinone on at least 6 occasions (two in the previous year) without serious&#xD;
             adverse reactions.&#xD;
&#xD;
          -  Extensive metabolizer or intermediate metabolizer phenotype for cytochrome P-450-2D6&#xD;
             (CYP2D6) activity determined using dextromethorphan as a selective probe drug.&#xD;
&#xD;
          -  The weight does not exceed 15% of ideal weight that applies according to size and will&#xD;
             be between 60 and 100 Kg. Minor variations will be accepted as normal limits, if the&#xD;
             researchers considered it clinically insignificant.&#xD;
&#xD;
        Exclusion Criteria:.&#xD;
&#xD;
          -  Daily consumption &gt;20 cigarettes and &gt;4 standard units of ethanol.&#xD;
&#xD;
          -  Regular use of any drug in the month prior to the study sessions. The treatment with&#xD;
             single or limited doses of symptomatic medicinal products in the week prior to the&#xD;
             study sessions will not be a reason for exclusion if it is calculated that it has been&#xD;
             cleared completely the day of the experimental session.&#xD;
&#xD;
          -  Presence of major psychiatric disorders.&#xD;
&#xD;
          -  Present history of abuse or drug dependence (except for nicotine dependence).&#xD;
&#xD;
          -  Past history of drug dependence (except for nicotine dependence). Subjects with past&#xD;
             history of drug abuse could be included.&#xD;
&#xD;
          -  Having suffered any organic disease or major surgery in the three months prior to the&#xD;
             study start.&#xD;
&#xD;
          -  Blood donation 12 weeks before or participation in other clinical trials with drugs in&#xD;
             the previous 4 weeks.&#xD;
&#xD;
          -  Subjects with intolerance or serious adverse reactions to drugs or amphetamines,&#xD;
             ecstasy and hallucinogen derivatives, mephedrone or other cathinone.&#xD;
&#xD;
          -  History or clinical evidence of gastrointestinal, liver, renal or other disorders&#xD;
             which may lead to suspecting a disorder in drug absorption, distribution, metabolism&#xD;
             or excretion, or that suggest gastrointestinal irritation due to drugs.&#xD;
&#xD;
          -  Subjects unable to understand the nature, consequences of the study and the procedures&#xD;
             requested to be followed.&#xD;
&#xD;
          -  Subjects with positive serology to Hepatitis B, C or HIV.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Magi Farre, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Parc de Salut Mar</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut Hospital del Mar d'Investigacions Mèdiques-IMIM. Parc de Salut Mar.</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>December 3, 2014</last_update_submitted>
  <last_update_submitted_qc>December 3, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 4, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mephedrone</keyword>
  <keyword>3,4-methylenedioxymethamphetamine</keyword>
  <keyword>Abuse liability</keyword>
  <keyword>Human Pharmacology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amphetamine-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>N-Methyl-3,4-methylenedioxyamphetamine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02232789
org study id: IMIMFTCL/MEF/1
nct id: NCT02232789
lead sponsor: 
collaborator: 
has dmc: Yes
The purposes of this study are 1) to evaluate the abuse liability and human pharmacology of
      mephedrone after oral administration and 2) to compare the pharmacological effects of
      mephedrone with those obtained after administration of oral 3,4-methylenedioxymethamphetamine
      (MDMA, ecstasy).
Mephedrone is a new psychoactive substance (NPS). At present, there are no randomized
      controlled trials evaluating the effects of mephedrone in humans. The current body of
      knowledge regarding the acute effects of mephedrone is based on anecdotal, self-reported
      effects (e.g. internet forums), case reports, and emergency room series and fatalities.

      The aims of this study are 1) to evaluate the abuse liability and human pharmacology of
      mephedrone after oral administration and 2) to compare the pharmacological effects of
      mephedrone with those obtained after administration of oral 3,4-methylenedioxymethamphetamine
      (MDMA, ecstasy).
allocation: Randomized
intervention model: Crossover Assignment
masking: Double (Participant, Investigator)
measure: Changes in blood pressure
time frame: From pre-dose (baseline) to 4h post-dose
description: Systolic and diastolic blood pressure
measure: Changes in euphoria-good effects
time frame: From pre-dose (baseline) to 4h post-dose
description: Euphoria-good effects effects will be measured using rating scales (visual analogue scales, the Addiction Research Center Inventory and the Evaluation of the Subjective Effects of Substances with Abuse Potential questionnaires). All these instruments include measures of euphoria-good effects and other feelings induced by psychostimulants
measure: Area Under the Concentration-Time Curve (AUC 0-24h)
time frame: From baseline (pre-dose, 0h) to 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24h post-dose
description: Calculation of AUC of the concentrations of mephedrone and MDMA and its metabolites in blood, urine, oral fluid and sweat.
measure: Number of Participants with Serious and Non-Serious Adverse Events
time frame: 7 days after each substance administration
description: Collection of adverse effects spontaneously reported by the participants and/or observed by the investigators
measure: Elimination half-life
time frame: From baseline to 24h post-dose
description: Calculation of elimination hal-life from concentrations of mephedrone, MDMA and its metabolites in plasma-blood, urine, oral fluid and sweat.
measure: Changes in heart rate
time frame: From pre-dose (baseline) to 4h post-dose
description: Measure of heart rate (pulse)
measure: Changes in pupil diameter
time frame: From pre-dose (baseline) to 4h post-dose
description: Measure of pupil diameter and capacity of convergence (esophoria) using a pupillometer
measure: Changes in oral temperature
time frame: From pre-dose (baseline) to 4h post-dose
description: Measure of temperature in mouth using automatic thermometer
arm group label: Mephedrone
arm group type: Experimental
description: Mephedrone 200 mg, single dose, oral administration
arm group label: 3,4-methylenedioxymethamphetamine
arm group type: Active Comparator
description: 3,4-methylenedioxymethamphetamine (MDMA) 100 mg, single dose, oral administration
arm group label: Lactose
arm group type: Placebo Comparator
description: Placebo, single dose, oral administration
intervention type: Drug
intervention name: Mephedrone
description: Single oral dose mephedrone
arm group label: Mephedrone
other name: 4-methylmethcathinone
other name: 4-MMC
intervention type: Drug
intervention name: 3,4-methylenedioxymethamphetamine
description: Single oral dose MDMA
arm group label: 3,4-methylenedioxymethamphetamine
other name: MDMA
other name: Ecstasy
intervention type: Drug
intervention name: Placebo
description: Single oal dose placebo
arm group label: Lactose
other name: Non active treatment
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Magi Farre, MD, PhD
role: Principal Investigator
affiliation: Parc de Salut Mar
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Amphetamine-Related Disorders
mesh term: N-Methyl-3,4-methylenedioxyamphetamine