Clinical trial NCT02242656: 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
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 type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Short Bowel Syndrome
Short Gut Syndrome
SBS
Short Bowel
Short Gut
Keywords: 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
Lead sponsor: Marathon Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2014-09-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of responders between Treatments A and B for the Intent-To-Treat (ITT) population
timeFrame: Last day of Periods 1 (Days 16-17) and 2 (Days 25-26)
Secondary outcomes:
measure: Percentage of responders between Treatments A and B for the Modified-Intent-To-Treat (mITT) population
timeFrame: Last day of Periods 1 (Days 16-17) and 2 (Days 25-26)
measure: Establish non-inferiority of the percentage of responders between Treatment A and Treatment C
timeFrame: Last day of Period 3 (Day 34-35)
measure: 24-hour stool volume comparison between Treatment A and B for ITT and mITT
timeFrame: Last day of Periods 1 (Day 16-17) and 2 (Day 25-26)
measure: 24-hour fecal events between Treatment A and B for ITT and mITT
timeFrame: Period 1 (Day 10-16) and 2 (Day 19-25)
measure: 24-hour nocturnal fecal events between Treatment A and B for ITT and mITT
timeFrame: Period 1 (Day 10-16) and 2 (Day 19-25)
measure: Single and multiple dose Pharmacokinetic (PK) parameters
timeFrame: Day-1, Day 1, Day 7, Day 57-59
measure: Number of Participants with Adverse Events
timeFrame: Up to 60 Days
measure: Number of Participants Up-Titrated
timeFrame: Days 35-60
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Lima
country: United States
facility: Regional Infectious Diseases Infusion Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt Center for Human Nutrition
state: Tennessee
Study officials:
References: