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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Short Bowel Syndrome, Short Gut Syndrome, SBS, Short Bowel, Short Gut

Intervention / Treatment
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* Drug: Opium Tincture USP Deodorized
* Drug: Opium Tincture USP Deodorized


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be male or female adults, 18 years of age or older at the time of consent 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 Have a history of persistent loose stools for more than 4 weeks Be on a combination of Opium Tincture and an anti-diarrheal (loperamide or diphenoxylate) or an anti-diarrheal agent alone 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 Be able to maintain their current diet for the duration of the study Be on stable nutritional support (parenteral or oral) 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) Females of childbearing potential must agree to use 1 of the following acceptable birth control methods: Surgically sterile (hysterectomy or bilateral oophorectomy) Surgically sterile (bilateral tubal ligation with surgery at least 6 weeks prior to study initiation) Intrauterine device (IUD) in place for at least 3 months Abstinence (not having sexual intercourse) Barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening and through study completion Stable hormonal contraceptive for at least 3 months prior to study and through study completion Vasectomized partner Females of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at screening Be able to understand and provide signed informed consent Exclusion Criteria: Unable or unwilling to stop the use of Opium Tincture or any anti-diarrheal medication at the screening visit. 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 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 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 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 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) Have a known allergy or intolerance to Opium Tincture or any of the excipients in the formulation (alcohol, opium, or morphine) 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 Are currently taking antibiotics for bacterial overgrowth Have participated in another interventional clinical trial within 30 days prior to screening with the exception of observational cohort studies or non-interventional studies. Have known or suspected pregnancy, planned pregnancy, or lactation Have a planned surgery over the course of the study 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Assigned to receive Treatment A (Period 1), Treatment B (Period 2), Treatment C (Period 3) | Drug: Opium Tincture USP Deodorized<br>* 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<br>|
| Experimental: Group 2<br>Assigned to receive Treatment B (Period 1), Treatment A (Period 2), Treatment C (Period 3) | Drug: Opium Tincture USP Deodorized<br>* 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<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Short Bowel Syndrome, SBS, Chronic Diarrhea, Short Bowel, Short Gut, Short Gut Syndrome, Anti-Diarrheal, Opium Tincture, loperamide, diphenoxylate, ileostomies, tincture of opium, DTO, codeine, morphine, opiate