<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/NCT01665209</url>
  </required_header>
  <id_info>
    <org_study_id>AAI-US-455</org_study_id>
    <nct_id>NCT01665209</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Morphine Sulfate 60 mg Extended-Release Tablets Under Fed Conditions</brief_title>
  <official_title>Single Dose Two-Way Crossover Fed Bioequivalence Study of Morphine Sulfate 60 mg Extended-Release Tablets in Healthy Volunteers.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ranbaxy Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ranbaxy Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study was to evaluate the relative bioavailability of morphine and morphine-6-glucuronide&#xD;
      from 2 tablet products and determine if the 2 products were bioequivalent to each other.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a single center, single-dose, randomized, open-label, two-treatment, two-period&#xD;
      crossover bioequivalence study designed to evaluate the pharmacokinetics and bioequivalence&#xD;
      of morphine sulfate formulations under fed conditions. Normal healthy males and females at&#xD;
      least 18 years of age were screened for enrollment into the trial.&#xD;
&#xD;
      Potential subjects who met the eligibility criteria randomly received either oral Morphine&#xD;
      Sulfate 60 mg Extended-release tablets or oral MS Contin® 60 mg Controlled-release tablets on&#xD;
      Day 1 in Period 1, then, following the washout period, they were dosed on Day 8 in Period 2&#xD;
      with the other treatment. There was a 7-day washout period between dosing. The study drug&#xD;
      treatments were administered following the Food and Drug Administration (FDA) high-fat&#xD;
      breakfast, which was served after subjects had been fasting for 11 hours. Fasting resumed&#xD;
      until 4 hours post-dose for both treatment groups. All enrolled subjects were administered&#xD;
      single oral doses of 50 mg of naltrexone hydrochloride 10 hours predose, 1 hour predose, and&#xD;
      12 hours post-dose of the study drug treatment on Day -1 and Day 1 in Period 1 and on Day 7&#xD;
      and Day 8 in Period 2. Potential subjects (ie, alternates) were administered single oral&#xD;
      doses of 50 mg of naltrexone hydrochloride 10 hours predose and 1 hour predose of the study&#xD;
      drug treatment on Day -1 and Day 1 in Period 1.&#xD;
&#xD;
      Subjects visited the clinic at Screening (within 28 days prior to dosing) to assess&#xD;
      eligibility and returned to the clinic on Day -1 for the Period 1 confinement period that&#xD;
      lasted through Day 2. To complete Period 1, subjects were to return on Day 3 for the&#xD;
      collection of pharmacokinetic blood samples. Period 1 dosing was followed by the 7-day&#xD;
      washout period. Subjects returned to the clinic for the Period 2 confinement period on Day 7,&#xD;
      which continued through Day 9. To complete Period 2, subjects were to return on Day 10 in&#xD;
      that period for the collection of pharmacokinetic and safety blood samples.&#xD;
&#xD;
      Pharmacokinetic and safety assessments were performed during the conduct of the trial. Blood&#xD;
      samples for the evaluation of morphine and morphine-6-glucuronide plasma concentrations were&#xD;
      obtained while subjects were at the clinic and after discharge, as appropriate.&#xD;
      Pharmacokinetic samples were collected over a 48-hour period of time following administration&#xD;
      of the study drug treatment.&#xD;
&#xD;
      Medical care of the subjects was assured by the presence of a physician for at least 4 hours&#xD;
      post-dose, and the physician remained on-call to treat adverse events (AEs). Professional&#xD;
      medical personnel were on-site during the entire study confinement period. Adverse event&#xD;
      information elicited during confinement at the clinic or during telephone contacts was&#xD;
      reviewed and documented.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2006</start_date>
  <completion_date type="Actual">December 2006</completion_date>
  <primary_completion_date type="Actual">October 2006</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite of Pharmacokinetics</measure>
    <time_frame>predose and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.333, 3.667, 4, 5, 6, 8, 10, and 12 hours post-dose</time_frame>
    <description>Cmax, Area Under Curve and Tmax</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Morphine Sulfate 60mg Extended-release tablets</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single oral dose of Morphine Sulfate 60mg Extended-release tablets of Ohm Laboratories Inc.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MS Contin® 60 mg Controlled-release tablets</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A single oral dose of MS Contin® 60 mg Controlled-release tablets of Purdue Pharma L.P.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine Sulfate</intervention_name>
    <description>Morphine Sulfate 60mg Extended-release tablets</description>
    <arm_group_label>MS Contin® 60 mg Controlled-release tablets</arm_group_label>
    <arm_group_label>Morphine Sulfate 60mg Extended-release tablets</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For inclusion into the trial, subjects were required to fulfill all of the following&#xD;
        criteria:&#xD;
&#xD;
          1. Healthy subjects at least 18 years of age.&#xD;
&#xD;
          2. Willingness to provide written informed consent after being informed of the nature of&#xD;
             the study.&#xD;
&#xD;
          3. Body mass index (BMI) between 18 and 30 and a weight of at least 110 pounds.&#xD;
&#xD;
          4. Good health as determined by a lack of clinically significant abnormalities in health&#xD;
             assessments performed at Screening, as judged by the physician.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        ny of the following was regarding as a criterion for excluding subjects from the trial:&#xD;
&#xD;
          1. Hypersensitivity to morphine sulfate (MS Contin®), naltrexone (ReVia®), or related&#xD;
             compounds.&#xD;
&#xD;
          2. Conditions that affected the absorption, metabolism, or passage of drugs out of the&#xD;
             body (eg, sprue, celiac disease, Crohn's disease, colitis, liver, kidney, or thyroid&#xD;
             conditions).&#xD;
&#xD;
          3. Recent history (within 1 year) of mental illness, drug addiction, drug abuse, or&#xD;
             alcoholism.&#xD;
&#xD;
          4. A hematocrit value of ≤ 33.0% for females and ≤ 37.0% for males.&#xD;
&#xD;
          5. Donation of &gt; 500 mL of blood in the past 8 weeks prior to study drug dosing or&#xD;
             difficulty in donating blood.&#xD;
&#xD;
          6. Receipt of an investigational drug within the 4 weeks prior to study drug dosing.&#xD;
&#xD;
          7. Current use of any systemic prescription medications, except for&#xD;
             oral/cutaneous/vaginal/injectable hormone contraceptives, within the 7 days prior to&#xD;
             study drug dosing or over-the-counter (OTC) medication within 3 days of study drug&#xD;
             dosing.&#xD;
&#xD;
             This prohibition did not include vitamins or herbal preparations taken as nutritional&#xD;
             supplements for non-therapeutic indications, as judged by the attending physician.&#xD;
&#xD;
             Any nonprescription medication consumption reported was to be reviewed by the&#xD;
             investigator prior to dosing. At the discretion of the investigator, these volunteers&#xD;
             could be enrolled if the medication was not anticipated to alter study integrity or&#xD;
             the safety of the subject.&#xD;
&#xD;
          8. Regular smoking of more than 5 cigarettes weekly or the regular daily use of nicotine&#xD;
             containing products beginning 3 months before study drug administration through the&#xD;
             final evaluation.&#xD;
&#xD;
             Subjects had to be able to refrain from smoking while confined in the clinic.&#xD;
&#xD;
          9. Female subjects who were lactating or had a positive pregnancy test at Screening and&#xD;
             prior to each of the treatment periods.&#xD;
&#xD;
             Females were to use a medically acceptable method of contraception throughout the&#xD;
             entire study period and for 1 week after study completion. Medically acceptable&#xD;
             methods of contraception that could have been used by the subject and/or her partner&#xD;
             were oral contraceptives/patches, progestin injection or implants, condom with&#xD;
             spermicide, diaphragm with spermicide, intrauterine device (IUD), vaginal spermicidal&#xD;
             or hormonal suppository, surgical sterilization of themselves or their partner(s), or&#xD;
             abstinence. Females using contraceptive medications/devices must have used them&#xD;
             consistently for at least 3 months prior to receiving study drug.&#xD;
&#xD;
         10. Alcohol, grapefruit beverages or foods, caffeine, or xanthine beverages or foods&#xD;
             beginning 48 hours before each study drug administration through the last&#xD;
             pharmacokinetic (PK) sample of each treatment period.&#xD;
&#xD;
             Such restricted items included coffee, tea, iced tea, Coke®, Pepsi®, Mountain Dew®,&#xD;
             chocolate, brownies, etc.&#xD;
&#xD;
         11. Regular use of any drugs known to induce or inhibit hepatic drug metabolism (examples&#xD;
             include barbiturates, carbamazepine, rifampin, phenylhydantoins, phenothiazines,&#xD;
             cimetidine, omeprazole, macrolides, imidazoles, fluoroquinolones) within 30 days prior&#xD;
             to study drug administration.&#xD;
&#xD;
         12. Positive test results for human immunodeficiency virus (HIV), hepatitis B surface&#xD;
             antigen (HBsAg), and hepatitis C antibody at Screening.&#xD;
&#xD;
         13. Positive test results for drugs of abuse or pregnancy at Screening and prior to each&#xD;
             study drug dosing period.&#xD;
&#xD;
         14. Subjects having emesis after either dose of naltrexone administered prior to the study&#xD;
             drug were not to be continued in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>41 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://clinicalstudies.ranbaxy.com</url>
    <description>Related Info</description>
  </link>
  <link>
    <url>http://dailymed.nlm.nih.gov/dailymed/about.cfm</url>
    <description>Related Info</description>
  </link>
  <link>
    <url>http://www.fda.gov/opacom/7alerts.html</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2012</study_first_posted>
  <last_update_submitted>August 13, 2012</last_update_submitted>
  <last_update_submitted_qc>August 13, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 15, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</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/NCT01665209
org study id: AAI-US-455
nct id: NCT01665209
lead sponsor: 
has dmc: No
The study was to evaluate the relative bioavailability of morphine and morphine-6-glucuronide
      from 2 tablet products and determine if the 2 products were bioequivalent to each other.
This was a single center, single-dose, randomized, open-label, two-treatment, two-period
      crossover bioequivalence study designed to evaluate the pharmacokinetics and bioequivalence
      of morphine sulfate formulations under fed conditions. Normal healthy males and females at
      least 18 years of age were screened for enrollment into the trial.

      Potential subjects who met the eligibility criteria randomly received either oral Morphine
      Sulfate 60 mg Extended-release tablets or oral MS Contin® 60 mg Controlled-release tablets on
      Day 1 in Period 1, then, following the washout period, they were dosed on Day 8 in Period 2
      with the other treatment. There was a 7-day washout period between dosing. The study drug
      treatments were administered following the Food and Drug Administration (FDA) high-fat
      breakfast, which was served after subjects had been fasting for 11 hours. Fasting resumed
      until 4 hours post-dose for both treatment groups. All enrolled subjects were administered
      single oral doses of 50 mg of naltrexone hydrochloride 10 hours predose, 1 hour predose, and
      12 hours post-dose of the study drug treatment on Day -1 and Day 1 in Period 1 and on Day 7
      and Day 8 in Period 2. Potential subjects (ie, alternates) were administered single oral
      doses of 50 mg of naltrexone hydrochloride 10 hours predose and 1 hour predose of the study
      drug treatment on Day -1 and Day 1 in Period 1.

      Subjects visited the clinic at Screening (within 28 days prior to dosing) to assess
      eligibility and returned to the clinic on Day -1 for the Period 1 confinement period that
      lasted through Day 2. To complete Period 1, subjects were to return on Day 3 for the
      collection of pharmacokinetic blood samples. Period 1 dosing was followed by the 7-day
      washout period. Subjects returned to the clinic for the Period 2 confinement period on Day 7,
      which continued through Day 9. To complete Period 2, subjects were to return on Day 10 in
      that period for the collection of pharmacokinetic and safety blood samples.

      Pharmacokinetic and safety assessments were performed during the conduct of the trial. Blood
      samples for the evaluation of morphine and morphine-6-glucuronide plasma concentrations were
      obtained while subjects were at the clinic and after discharge, as appropriate.
      Pharmacokinetic samples were collected over a 48-hour period of time following administration
      of the study drug treatment.

      Medical care of the subjects was assured by the presence of a physician for at least 4 hours
      post-dose, and the physician remained on-call to treat adverse events (AEs). Professional
      medical personnel were on-site during the entire study confinement period. Adverse event
      information elicited during confinement at the clinic or during telephone contacts was
      reviewed and documented.
allocation: Randomized
intervention model: Crossover Assignment
masking: None (Open Label)
measure: Composite of Pharmacokinetics
time frame: predose and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.333, 3.667, 4, 5, 6, 8, 10, and 12 hours post-dose
description: Cmax, Area Under Curve and Tmax
arm group label: Morphine Sulfate 60mg Extended-release tablets
arm group type: Experimental
description: A single oral dose of Morphine Sulfate 60mg Extended-release tablets of Ohm Laboratories Inc.
arm group label: MS Contin® 60 mg Controlled-release tablets
arm group type: Active Comparator
description: A single oral dose of MS Contin® 60 mg Controlled-release tablets of Purdue Pharma L.P.
intervention type: Drug
intervention name: Morphine Sulfate
description: Morphine Sulfate 60mg Extended-release tablets
arm group label: MS Contin® 60 mg Controlled-release tablets
arm group label: Morphine Sulfate 60mg Extended-release tablets
criteria: 
gender: All
minimum age: 19 Years
maximum age: 41 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://clinicalstudies.ranbaxy.com
description: Related Info
url: http://dailymed.nlm.nih.gov/dailymed/about.cfm
description: Related Info
url: http://www.fda.gov/opacom/7alerts.html
description: Related Info
responsible party type: Sponsor
mesh term: Morphine