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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Short Bowel Syndrome; Short Gut Syndrome; SBS; Short Gut; Short Bowel
• Intervention / Treatment: Drug: Opium Tincture USP Deodorized; Drug: Opium Tincture USP Deodorized

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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; 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
Experimental: Group 2; Assigned to receive Treatment B (Period 1), Treatment A (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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of responders between Treatments A and B for the Intent-To-Treat (ITT) population	30% or greater reduction in 24-hour stool volume from baseline	Last day of Periods 1 (Days 16-17) and 2 (Days 25-26)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of responders between Treatments A and B for the Modified-Intent-To-Treat (mITT) population	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	Last day of Periods 1 (Days 16-17) and 2 (Days 25-26)
Establish non-inferiority of the percentage of responders between Treatment A and Treatment C	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)	Last day of Period 3 (Day 34-35)
24-hour stool volume comparison between Treatment A and B for ITT and mITT	Comparison of stool volume measurements	Last day of Periods 1 (Day 16-17) and 2 (Day 25-26)
24-hour fecal events between Treatment A and B for ITT and mITT	Changes in the number of 24-hour fecal events for ITT and mITT	Period 1 (Day 10-16) and 2 (Day 19-25)
24-hour nocturnal fecal events between Treatment A and B for ITT and mITT	Changes in the number of 24-hour nocturnal (ad defined for each subject) fecal events for ITT and mITT	Period 1 (Day 10-16) and 2 (Day 19-25)
Single and multiple dose Pharmacokinetic (PK) parameters	Evaluate the pharmacokinetics of morphine, codeine, thebaine and papaverine after single dose and multiple dose administration of MP-101	Day-1, Day 1, Day 7, Day 57-59
Number of Participants with Adverse Events	Review of safety events throughout the course of the study	Up to 60 Days
Number of Participants Up-Titrated	Review of safety events throughout the course of the study	Days 35-60

Collaborators and Investigators

• Sponsor: Marathon Pharmaceuticals, LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: September 10, 2014
• First Submitted That Met QC Criteria: September 15, 2014
• First Posted (Estimate): September 17, 2014

Study Record Updates

• Last Update Posted (Estimate): February 18, 2015
• Last Update Submitted That Met QC Criteria: February 16, 2015
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: morphine; loperamide; codeine; Short Bowel Syndrome; opiate; SBS; Chronic Diarrhea; Short Bowel; Short Gut; Short Gut Syndrome; Anti-Diarrheal; Opium Tincture; diphenoxylate; ileostomies; tincture of opium; DTO
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Disease; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Syndrome; Short Bowel Syndrome; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Gastrointestinal Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Antidiarrheals; Opium
• Other Study ID Numbers: MP-101-CL-001