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

Short Bowel Syndrome Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02242656
• Other study ID #: MP-101-CL-001
• Status: Withdrawn
• Phase: Phase 3
• First received: September 10, 2014
• Last updated: February 16, 2015
• Start date: December 2014

Study information

• Verified date: October 2014
• Source: Marathon Pharmaceuticals, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• SBS
• Short Bowel
• Short Bowel Syndrome
• Short Gut
• Short Gut Syndrome
• Syndrome

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Indiana University	Indianapolis	Indiana
United States	Regional Infectious Diseases Infusion Center	Lima	Ohio
United States	Vanderbilt Center for Human Nutrition	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Marathon Pharmaceuticals, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	Number of Participants with Adverse Events	Review of safety events throughout the course of the study	Up to 60 Days	Yes
Secondary	Number of Participants Up-Titrated	Review of safety events throughout the course of the study	Days 35-60	Yes