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Trial record 4 of 4 for:    Diphenoxylate OR DIPHENOXYLATE HYDROCHLORIDE OR DIPHENOXYLATE

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

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ClinicalTrials.gov Identifier: NCT02242656
Recruitment Status : Withdrawn (Transfer of IND to new marketing authorization holder)
First Posted : September 17, 2014
Last Update Posted : February 18, 2015
Sponsor:
Information provided by (Responsible Party):
Marathon Pharmaceuticals, LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Short Bowel Syndrome Short Gut Syndrome SBS Short Bowel Short Gut Drug: Opium Tincture USP Deodorized Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : December 2014
Estimated Primary Completion Date : December 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group 1
Assigned to receive Treatment A (Period 1), Treatment B (Period 2), Treatment C (Period 3)
Drug: Opium Tincture USP Deodorized
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

Experimental: Group 2
Assigned to receive Treatment B (Period 1), Treatment A (Period 2), Treatment C (Period 3)
Drug: Opium Tincture USP Deodorized
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




Primary Outcome Measures :
  1. 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) ]
    30% or greater reduction in 24-hour stool volume from baseline


Secondary Outcome Measures :
  1. 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) ]
    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

  2. Establish non-inferiority of the percentage of responders between Treatment A and Treatment C [ Time Frame: Last day of Period 3 (Day 34-35) ]
    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)

  3. 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) ]
    Comparison of stool volume measurements

  4. 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) ]
    Changes in the number of 24-hour fecal events for ITT and mITT

  5. 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) ]
    Changes in the number of 24-hour nocturnal (ad defined for each subject) fecal events for ITT and mITT

  6. Single and multiple dose Pharmacokinetic (PK) parameters [ Time Frame: Day-1, Day 1, Day 7, Day 57-59 ]
    Evaluate the pharmacokinetics of morphine, codeine, thebaine and papaverine after single dose and multiple dose administration of MP-101

  7. Number of Participants with Adverse Events [ Time Frame: Up to 60 Days ]
    Review of safety events throughout the course of the study

  8. Number of Participants Up-Titrated [ Time Frame: Days 35-60 ]
    Review of safety events throughout the course of the study



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be male or female adults, 18 years of age or older at the time of consent
  2. Have SBS that is inadequately controlled on current antidiarrheal medication (e.g., loperamide or diphenoxylate), including subjects with ileostomies, based on the 7 days prior to Day 1 of the study

    a. Subjects must be >3months post intestinal resection

  3. Have a history of persistent loose stools for more than 4 weeks
  4. Be on a combination of Opium Tincture and an anti-diarrheal (loperamide or diphenoxylate) or an anti-diarrheal agent alone
  5. If currently taking Opium Tincture, be willing to stop the continued use of Opium Tincture at screening visit until the start of study treatment and willing to stop the use of any other anti-diarrheal for the duration of the study
  6. Be able to maintain their current diet for the duration of the study
  7. Be on stable nutritional support (parenteral or oral)
  8. Males or non-pregnant, non-lactating females who are postmenopausal, naturally or surgically sterile, or who agree to use effective contraceptive methods throughout the course of the study. Postmenopausal is defined as at least 12 months of natural spontaneous amenorrhea, or at least 6 weeks following surgical menopause (bilateral oophorectomy)
  9. Females of childbearing potential must agree to use 1 of the following acceptable birth control methods:

    1. Surgically sterile (hysterectomy or bilateral oophorectomy)
    2. Surgically sterile (bilateral tubal ligation with surgery at least 6 weeks prior to study initiation)
    3. Intrauterine device (IUD) in place for at least 3 months
    4. Abstinence (not having sexual intercourse)
    5. Barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening and through study completion
    6. Stable hormonal contraceptive for at least 3 months prior to study and through study completion
    7. Vasectomized partner
  10. Females of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at screening
  11. Be able to understand and provide signed informed consent

Exclusion Criteria:

  1. Unable or unwilling to stop the use of Opium Tincture or any anti-diarrheal medication at the screening visit.
  2. Have any history of or active neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, or metabolic disease that is considered clinically significant, is not currently controlled by medication, and is stable as deemed by the Investigator
  3. Have clinically significant electrocardiogram (ECG) abnormalities as determined by the PI or vital sign abnormalities (systolic blood pressure < 90 mmHg, diastolic blood pressure < 60 mmHg, or heart rate >100 bpm) at screening
  4. Have clinically significant elevation of liver enzymes (> 3 times the upper limit of normal) or clinically relevant renal disease, (creatinine >1.5) or any other clinically significant abnormal laboratory test results found during medical screening as determined by the Principal Investigator
  5. Have a history of major mental illness that in the opinion of the Investigator may affect the ability of the subject to safely participate and reliably complete the study
  6. Have a history of alcohol or substance abuse within the past 2 years. Alcohol abuse will be defined as >14 drinks per week (1 drink = 12 oz. beer, 5.0 oz. wine, or 1.5 oz. distilled spirits)
  7. Have a known allergy or intolerance to Opium Tincture or any of the excipients in the formulation (alcohol, opium, or morphine)
  8. Is currently taking an opioid derivative (other than Opium Tincture) or any other medication which, in the opinion of the investigator, could interfere with the interpretation of the study results
  9. Are currently taking antibiotics for bacterial overgrowth
  10. Have participated in another interventional clinical trial within 30 days prior to screening with the exception of observational cohort studies or non-interventional studies.
  11. Have known or suspected pregnancy, planned pregnancy, or lactation
  12. Have a planned surgery over the course of the study
  13. Have a condition the Investigator believes would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the subject at undue risk

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02242656


Locations
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United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Regional Infectious Diseases Infusion Center
Lima, Ohio, United States, 45801
United States, Tennessee
Vanderbilt Center for Human Nutrition
Nashville, Tennessee, United States, 37212-1150
Sponsors and Collaborators
Marathon Pharmaceuticals, LLC

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Responsible Party: Marathon Pharmaceuticals, LLC
ClinicalTrials.gov Identifier: NCT02242656     History of Changes
Other Study ID Numbers: MP-101-CL-001
First Posted: September 17, 2014    Key Record Dates
Last Update Posted: February 18, 2015
Last Verified: October 2014

Keywords provided by Marathon Pharmaceuticals, LLC:
diphenoxylate
Short Bowel Syndrome
SBS
Chronic Diarrhea
Short Bowel
Short Gut
Short Gut Syndrome
Anti-Diarrheal
Opium Tincture
loperamide
ileostomies
tincture of opium
DTO
codeine
morphine
opiate

Additional relevant MeSH terms:
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Syndrome
Short Bowel Syndrome
Disease
Pathologic Processes
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Postoperative Complications
Opium
Antidiarrheals
Loperamide
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Antitussive Agents
Respiratory System Agents