<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/NCT02242656</url>
  </required_header>
  <id_info>
    <org_study_id>MP-101-CL-001</org_study_id>
    <nct_id>NCT02242656</nct_id>
  </id_info>
  <brief_title>A Phase III Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Investigational Product MP-101 in Subjects With Short Bowel Syndrome Who Have Had an Inadequate Response to Anti-Diarrheals</brief_title>
  <official_title>A Phase 3, Open Label Responder Treatment Period With a Randomized, Blinded, Three-Period Crossover, Followed by an Open Label Safety Period to Evaluate the Clinical Efficacy, Safety, and Pharmacokinetics of Investigational Drug MP-101 (Opium Tincture and Opium Tincture With Reduced Uncharacterized Material) to Treat Chronic Diarrhea in Subjects With Short Bowel Syndrome Who Have Had an Inadequate Response to Anti-Diarrheals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Marathon Pharmaceuticals, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Marathon Pharmaceuticals, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      MP-101 will be evaluated in this study to see if it is safe, tolerable, and can help people&#xD;
      with Short Bowel Syndrome. This study will also find out if taking MP-101 can improve the&#xD;
      symptoms of Short Bowel Syndrome and reduce the number of times subjects experience bowel&#xD;
      movements.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Transfer of IND to new marketing authorization holder&#xD;
  </why_stopped>
  <start_date>December 2014</start_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of responders between Treatments A and B for the Intent-To-Treat (ITT) population</measure>
    <time_frame>Last day of Periods 1 (Days 16-17) and 2 (Days 25-26)</time_frame>
    <description>30% or greater reduction in 24-hour stool volume from baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of responders between Treatments A and B for the Modified-Intent-To-Treat (mITT) population</measure>
    <time_frame>Last day of Periods 1 (Days 16-17) and 2 (Days 25-26)</time_frame>
    <description>30% or greater reduction in 24-hour stool volume from baseline for subjects who complete both periods 1 and 2 of the randomized, blinded, crossover portion of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Establish non-inferiority of the percentage of responders between Treatment A and Treatment C</measure>
    <time_frame>Last day of Period 3 (Day 34-35)</time_frame>
    <description>30% or greater reduction in stool volume from baseline between Treatment A (with uncharacterized material) and Treatment C (with reduced uncharacterized material) for ITT and mITT efficacy population (subjects from the ITT population who complete both Treatments A and C)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>24-hour stool volume comparison between Treatment A and B for ITT and mITT</measure>
    <time_frame>Last day of Periods 1 (Day 16-17) and 2 (Day 25-26)</time_frame>
    <description>Comparison of stool volume measurements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>24-hour fecal events between Treatment A and B for ITT and mITT</measure>
    <time_frame>Period 1 (Day 10-16) and 2 (Day 19-25)</time_frame>
    <description>Changes in the number of 24-hour fecal events for ITT and mITT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>24-hour nocturnal fecal events between Treatment A and B for ITT and mITT</measure>
    <time_frame>Period 1 (Day 10-16) and 2 (Day 19-25)</time_frame>
    <description>Changes in the number of 24-hour nocturnal (ad defined for each subject) fecal events for ITT and mITT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Single and multiple dose Pharmacokinetic (PK) parameters</measure>
    <time_frame>Day-1, Day 1, Day 7, Day 57-59</time_frame>
    <description>Evaluate the pharmacokinetics of morphine, codeine, thebaine and papaverine after single dose and multiple dose administration of MP-101</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events</measure>
    <time_frame>Up to 60 Days</time_frame>
    <description>Review of safety events throughout the course of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Up-Titrated</measure>
    <time_frame>Days 35-60</time_frame>
    <description>Review of safety events throughout the course of the study</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Short Bowel Syndrome</condition>
  <condition>Short Gut Syndrome</condition>
  <condition>SBS</condition>
  <condition>Short Bowel</condition>
  <condition>Short Gut</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Assigned to receive Treatment A (Period 1), Treatment B (Period 2), Treatment C (Period 3)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Assigned to receive Treatment B (Period 1), Treatment A (Period 2), Treatment C (Period 3)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Opium Tincture USP Deodorized</intervention_name>
    <description>Treatment A - 0.6 mL, MP-101 (10 mg/mL, Opium Tincture (OT)), USP (Deodorized) QID oral drops, followed by Treatment B - 0.6 mL, MP-101, 1/12 dilution, (0.833 mg/mL, OT), USP (Deodorized) QID oral drops, followed by Treatment C - 0.6 mL, MP-101 (10 mg/mL Opium Tincture with reduced uncharacterized material) QID oral drops</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Opium Tincture USP Deodorized</intervention_name>
    <description>Treatment B - 0.6 mL, MP-101, 1/12 dilution, (0.833 mg/mL, OT), USP (Deodorized) QID oral drops, followed by Treatment A - 0.6 mL, MP-101 (10 mg/mL, Opium Tincture (OT)), USP (Deodorized) QID oral drops, followed by Treatment C - 0.6 mL, MP-101 (10 mg/mL Opium Tincture with reduced uncharacterized material) QID oral drops</description>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Be male or female adults, 18 years of age or older at the time of consent&#xD;
&#xD;
          2. Have SBS that is inadequately controlled on current antidiarrheal medication (e.g.,&#xD;
             loperamide or diphenoxylate), including subjects with ileostomies, based on the 7 days&#xD;
             prior to Day 1 of the study&#xD;
&#xD;
             a. Subjects must be &gt;3months post intestinal resection&#xD;
&#xD;
          3. Have a history of persistent loose stools for more than 4 weeks&#xD;
&#xD;
          4. Be on a combination of Opium Tincture and an anti-diarrheal (loperamide or&#xD;
             diphenoxylate) or an anti-diarrheal agent alone&#xD;
&#xD;
          5. If currently taking Opium Tincture, be willing to stop the continued use of Opium&#xD;
             Tincture at screening visit until the start of study treatment and willing to stop the&#xD;
             use of any other anti-diarrheal for the duration of the study&#xD;
&#xD;
          6. Be able to maintain their current diet for the duration of the study&#xD;
&#xD;
          7. Be on stable nutritional support (parenteral or oral)&#xD;
&#xD;
          8. Males or non-pregnant, non-lactating females who are postmenopausal, naturally or&#xD;
             surgically sterile, or who agree to use effective contraceptive methods throughout the&#xD;
             course of the study. Postmenopausal is defined as at least 12 months of natural&#xD;
             spontaneous amenorrhea, or at least 6 weeks following surgical menopause (bilateral&#xD;
             oophorectomy)&#xD;
&#xD;
          9. Females of childbearing potential must agree to use 1 of the following acceptable&#xD;
             birth control methods:&#xD;
&#xD;
               1. Surgically sterile (hysterectomy or bilateral oophorectomy)&#xD;
&#xD;
               2. Surgically sterile (bilateral tubal ligation with surgery at least 6 weeks prior&#xD;
                  to study initiation)&#xD;
&#xD;
               3. Intrauterine device (IUD) in place for at least 3 months&#xD;
&#xD;
               4. Abstinence (not having sexual intercourse)&#xD;
&#xD;
               5. Barrier method (condom or diaphragm) with spermicide for at least 14 days prior&#xD;
                  to screening and through study completion&#xD;
&#xD;
               6. Stable hormonal contraceptive for at least 3 months prior to study and through&#xD;
                  study completion&#xD;
&#xD;
               7. Vasectomized partner&#xD;
&#xD;
         10. Females of childbearing potential must have a negative serum human chorionic&#xD;
             gonadotropin (hCG) pregnancy test at screening&#xD;
&#xD;
         11. Be able to understand and provide signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unable or unwilling to stop the use of Opium Tincture or any anti-diarrheal medication&#xD;
             at the screening visit.&#xD;
&#xD;
          2. Have any history of or active neurological, endocrine, cardiovascular, pulmonary,&#xD;
             hematological, immunologic, psychiatric, or metabolic disease that is considered&#xD;
             clinically significant, is not currently controlled by medication, and is stable as&#xD;
             deemed by the Investigator&#xD;
&#xD;
          3. Have clinically significant electrocardiogram (ECG) abnormalities as determined by the&#xD;
             PI or vital sign abnormalities (systolic blood pressure &lt; 90 mmHg, diastolic blood&#xD;
             pressure &lt; 60 mmHg, or heart rate &gt;100 bpm) at screening&#xD;
&#xD;
          4. Have clinically significant elevation of liver enzymes (&gt; 3 times the upper limit of&#xD;
             normal) or clinically relevant renal disease, (creatinine &gt;1.5) or any other&#xD;
             clinically significant abnormal laboratory test results found during medical screening&#xD;
             as determined by the Principal Investigator&#xD;
&#xD;
          5. Have a history of major mental illness that in the opinion of the Investigator may&#xD;
             affect the ability of the subject to safely participate and reliably complete the&#xD;
             study&#xD;
&#xD;
          6. Have a history of alcohol or substance abuse within the past 2 years. Alcohol abuse&#xD;
             will be defined as &gt;14 drinks per week (1 drink = 12 oz. beer, 5.0 oz. wine, or 1.5&#xD;
             oz. distilled spirits)&#xD;
&#xD;
          7. Have a known allergy or intolerance to Opium Tincture or any of the excipients in the&#xD;
             formulation (alcohol, opium, or morphine)&#xD;
&#xD;
          8. Is currently taking an opioid derivative (other than Opium Tincture) or any other&#xD;
             medication which, in the opinion of the investigator, could interfere with the&#xD;
             interpretation of the study results&#xD;
&#xD;
          9. Are currently taking antibiotics for bacterial overgrowth&#xD;
&#xD;
         10. Have participated in another interventional clinical trial within 30 days prior to&#xD;
             screening with the exception of observational cohort studies or non-interventional&#xD;
             studies.&#xD;
&#xD;
         11. Have known or suspected pregnancy, planned pregnancy, or lactation&#xD;
&#xD;
         12. Have a planned surgery over the course of the study&#xD;
&#xD;
         13. Have a condition the Investigator believes would interfere with the ability to provide&#xD;
             informed consent or comply with study instructions, or that might confound the&#xD;
             interpretation of the study results or put the subject at undue risk&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Northwestern University Feinberg School of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Infectious Diseases Infusion Center</name>
      <address>
        <city>Lima</city>
        <state>Ohio</state>
        <zip>45801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt Center for Human Nutrition</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212-1150</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>September 10, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <last_update_submitted>February 16, 2015</last_update_submitted>
  <last_update_submitted_qc>February 16, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 18, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Short Bowel Syndrome</keyword>
  <keyword>SBS</keyword>
  <keyword>Chronic Diarrhea</keyword>
  <keyword>Short Bowel</keyword>
  <keyword>Short Gut</keyword>
  <keyword>Short Gut Syndrome</keyword>
  <keyword>Anti-Diarrheal</keyword>
  <keyword>Opium Tincture</keyword>
  <keyword>loperamide</keyword>
  <keyword>diphenoxylate</keyword>
  <keyword>ileostomies</keyword>
  <keyword>tincture of opium</keyword>
  <keyword>DTO</keyword>
  <keyword>codeine</keyword>
  <keyword>morphine</keyword>
  <keyword>opiate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Short Bowel Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opium</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/NCT02242656
org study id: MP-101-CL-001
nct id: NCT02242656
lead sponsor: 
has dmc: No
MP-101 will be evaluated in this study to see if it is safe, tolerable, and can help people
      with Short Bowel Syndrome. This study will also find out if taking MP-101 can improve the
      symptoms of Short Bowel Syndrome and reduce the number of times subjects experience bowel
      movements.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Percentage of responders between Treatments A and B for the Intent-To-Treat (ITT) population
time frame: Last day of Periods 1 (Days 16-17) and 2 (Days 25-26)
description: 30% or greater reduction in 24-hour stool volume from baseline
measure: Percentage of responders between Treatments A and B for the Modified-Intent-To-Treat (mITT) population
time frame: Last day of Periods 1 (Days 16-17) and 2 (Days 25-26)
description: 30% or greater reduction in 24-hour stool volume from baseline for subjects who complete both periods 1 and 2 of the randomized, blinded, crossover portion of the study
measure: Establish non-inferiority of the percentage of responders between Treatment A and Treatment C
time frame: Last day of Period 3 (Day 34-35)
description: 30% or greater reduction in stool volume from baseline between Treatment A (with uncharacterized material) and Treatment C (with reduced uncharacterized material) for ITT and mITT efficacy population (subjects from the ITT population who complete both Treatments A and C)
measure: 24-hour stool volume comparison between Treatment A and B for ITT and mITT
time frame: Last day of Periods 1 (Day 16-17) and 2 (Day 25-26)
description: Comparison of stool volume measurements
measure: 24-hour fecal events between Treatment A and B for ITT and mITT
time frame: Period 1 (Day 10-16) and 2 (Day 19-25)
description: Changes in the number of 24-hour fecal events for ITT and mITT
measure: 24-hour nocturnal fecal events between Treatment A and B for ITT and mITT
time frame: Period 1 (Day 10-16) and 2 (Day 19-25)
description: Changes in the number of 24-hour nocturnal (ad defined for each subject) fecal events for ITT and mITT
measure: Single and multiple dose Pharmacokinetic (PK) parameters
time frame: Day-1, Day 1, Day 7, Day 57-59
description: Evaluate the pharmacokinetics of morphine, codeine, thebaine and papaverine after single dose and multiple dose administration of MP-101
measure: Number of Participants with Adverse Events
time frame: Up to 60 Days
description: Review of safety events throughout the course of the study
measure: Number of Participants Up-Titrated
time frame: Days 35-60
description: Review of safety events throughout the course of the study
arm group label: Group 1
arm group type: Experimental
description: Assigned to receive Treatment A (Period 1), Treatment B (Period 2), Treatment C (Period 3)
arm group label: Group 2
arm group type: Experimental
description: Assigned to receive Treatment B (Period 1), Treatment A (Period 2), Treatment C (Period 3)
intervention type: Drug
intervention name: Opium Tincture USP Deodorized
description: Treatment A - 0.6 mL, MP-101 (10 mg/mL, Opium Tincture (OT)), USP (Deodorized) QID oral drops, followed by Treatment B - 0.6 mL, MP-101, 1/12 dilution, (0.833 mg/mL, OT), USP (Deodorized) QID oral drops, followed by Treatment C - 0.6 mL, MP-101 (10 mg/mL Opium Tincture with reduced uncharacterized material) QID oral drops
arm group label: Group 1
intervention type: Drug
intervention name: Opium Tincture USP Deodorized
description: Treatment B - 0.6 mL, MP-101, 1/12 dilution, (0.833 mg/mL, OT), USP (Deodorized) QID oral drops, followed by Treatment A - 0.6 mL, MP-101 (10 mg/mL, Opium Tincture (OT)), USP (Deodorized) QID oral drops, followed by Treatment C - 0.6 mL, MP-101 (10 mg/mL Opium Tincture with reduced uncharacterized material) QID oral drops
arm group label: Group 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Short Bowel Syndrome
mesh term: Syndrome
mesh term: Opium