Safety and Preliminary Efficacy of BGP345A in Constipation Due to Opioid-based Medications (OIC1)

• ClinicalTrials.gov Identifier: NCT05133076
• Recruitment Status: Recruiting
• First Posted: November 24, 2021
• Last Update Posted: February 14, 2023
• Sponsor: BioGaia Pharma AB
• Collaborator: BioFortis
• Information provided by (Responsible Party): BioGaia Pharma AB

Tracking Information

• First Submitted Date: October 26, 2021
• First Posted Date: November 24, 2021
• Last Update Posted Date: February 14, 2023
• Actual Study Start Date: January 20, 2022
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 12, 2021)

Change in the average weekly number of Spontaneous Bowel Movements (SBMs) (expressed in number of stools/week) [ Time Frame: Over the 4 week treatment period ]

A SBM (Spontaneous Bowel Movement) is defined as a bowel movement without the use of laxatives in the previous 24 hours as recorded in the daily diary (Webster LR et al, 2017).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 12, 2021)

• Percentage of responders over the 4-weeks of treatment period defined by subjects reporting an average weekly number of SBMs ≥ 3 and an increase of the average weekly number of SBM ≥1 from baseline [ Time Frame: Average over the last two weeks of treatment ]
  SBM responders
• Change in the average weekly number of BMs (Bowel Movements) [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  BM (Bowel Movements) expressed in number of stools/week
• Change in the average weekly number of CSBMs (Complete Spontaneous Bowel Movement) [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  CSBMs (Complete Spontaneous Bowel Movement) expressed in number of stools/week is defined by as a bowel movement without the use of laxatives in the previous 24 hours as recorded in the daily diary and the feeling of complete emptying after bowel movement.
• Change in the average weekly number of SBMs [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  SBMs expressed in number of stools/week
• Change in the average weekly number of SBMs with no straining (straining score 1) [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  SBMs expressed in number of stools/week
• Time to first SBM and CSBM after the last recorded stool before the randomisation [ Time Frame: Over 4 week treatment period ]
  Expressed in hours
• Change in the number of days with presence of SBMs [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  SBMs expressed in days/week
• Change in the number of days with presence of CSBMs [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  CSBMs expressed in days/week
• Change in the average weekly number of SBMs rated 3 or 4 on the BSS (Bristol Stool Scale) [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  Expressed in stools/week
• Change of stool consistency assessed by the BSS (Bristol Stool Scale) [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  Expressed in arbitrary units/stool from 1-7.
• Change of the overall BFI (Bowel Function Index) score [ Time Frame: Over 4 week treatment period ]
  Expressed in arbitrary units, range 0-100
• Change in the average daily abdominal bloating score [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  Expressed in arbitrary units/day (this score will be assessed daily for the past 24hours and could range from 0 to 4, where 0 = absent or no bloating, 1 = mild, 2 = moderate, 3= severe, and 4 =very severe bloating)
• Change in the average daily abdominal discomfort score [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  Expressed in arbitrary units/day (this score will be assessed daily for the past 24hours and could range from 0 to 4, where 0 = no abdominal discomfort, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe discomfort)
• Change in average daily pain at defecation assessed by the Visual Analogic Scale for pain at defecation (VAS) [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  Expressed in arbitrary units/day with stool, range 0-100
• Change in the weekly frequency of rescue laxative use assessed by the daily diary [ Time Frame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion. ]
  expressed in average of days/week
• Frequency of rescue laxative use assessed by the daily diary. [ Time Frame: Over the 4 week treatment period ]
  Expressed in number of laxative uses
• General health state measuring vital parameters assessed - Body weight [ Time Frame: Through study completion, 10 weeks ]
  Body weight (kg)
• General health state measuring vital parameters assessed- Diastolic Blood Pressure [ Time Frame: Through study completion, 10 weeks ]
  Diastolic Blood Pressure (mmHg)
• General health state measuring vital parameters assessed- Systolic Blood Pressure [ Time Frame: Through study completion, 10 weeks ]
  Systolic Blood Pressure (mmHg)
• General health state measuring vital parameters assessed- Vital signs [ Time Frame: Through study completion, 10 weeks ]
  Vital signs (BPM)
• the frequency of adverse events (AE), serious adverse events (SAE), Treatment-Emergent Adverse events (TEAE), Serious treatment-emergent adverse events (STEAE) [ Time Frame: Through study completion, 10 weeks ]
  Frequency and nature of events

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Preliminary Efficacy of BGP345A in Constipation Due to Opioid-based Medications
• Official Title: A Randomized Placebo-controlled Study to Assess Safety and Preliminary Efficacy of BGP345A in Patients With Constipation Due to the Use of Opioid-based Medications for the Management of Chronic Non Cancer Pain
• Brief Summary: The purpose of this study is to assess safety and preliminary efficacy of BGP345A in patients with constipation due to the use of opioid-based medications for the management of chronic non cancer pain.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Opioid-Induced Constipation

Intervention

• Biological: Lactobacillus gasseri DSM 27123
  Active and placebo capsules for oral use
  Other Name: BGP345A
• Biological: Placebo
  Placebo

Study Arms

• Active Comparator: Active arm
  Intervention: Biological: Lactobacillus gasseri DSM 27123
• Placebo Comparator: Placebo arm
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 12, 2021): 126
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

I1. Age over 18 years (limit included),

I2. Diagnosed with OIC according to the adapted ROME IV criteria (Mearin F et al, 2016) previously used in clinical evaluation of patients with OIC (Webster LR et al, 2017) and self-reported symptoms assessed by a physician (daily diary check at V1 visit):

• Fewer than three (<3) spontaneous bowel movements (SBMs) per week. A SBM is defined as a bowel movement without the use of laxatives in the previous 24 hours as recorded in the daily diary.
• And one or more of the following symptoms in at least 25% of bowel movements: straining, feeling of incomplete evacuation, and/or hard/small stools, defined as Bristol Stool Scale (BSS) score lower than 3 (<3).

I3. With chronic non-cancer pain since at least three months, including the following indications but not limited to: back-pain, rheumatisms and post-operative pain,

I4. Patients received opioids for chronic analgesia (intended treatment ≥6 Weeks) for 1 week or more prior to study start and a stable regimen of opioids for 3 or more days before study entry (V0 visit) and during the whole study ,

I5. Subjects must be willing to discontinue laxative use at screening and only use the rescue laxatives permitted throughout the study duration,

I6. For women:

• Non menopausal with the same reliable contraception since at least 2 cycles before the beginning of the study and agreeing to keep it during the entire duration of the study (condom with spermicide gel, any oral contraceptive, intrauterine device, subcutaneous contraceptive implant, vaginal ring, surgical intervention (bilateral tubal ligation or ovariectomy or hysterectomy), ESSURE system),
• Menopausal without or with hormone replacement therapy,

I7. Good general and mental health with in the opinion of the investigator: no clinically significant and relevant abnormalities of medical history or physical examination,

I8. Able and willing to participate to the study by complying with the protocol procedures as evidenced by his dated and signed informed consent form,

I9. Affiliated with a social security scheme.

Exclusion Criteria:

E1. Involvement in any investigational drug or device study within 30 days prior to this study,

E2. Unable to withdraw other OIC treatments (any kind of laxative other than provided in the study),

E3. History of chronic constipation prior to starting analgesic medication or any potential non-opioid cause of bowel dysfunction that may be a major contributor to the constipation upon investigator judgment,

E4. Surgery planned within the whole study period,

E5. Evidence of active medical diseases affecting bowel transit,

E6. Antibiotic treatment intake within the last month prior the study start (V0),

E7. Unwilling to withdraw probiotic supplements, yoghurts without supplemented bacteria are permitted,

E8. Any history of drug addiction in the past five years,

E9. Pregnant or lactating women or intending to become pregnant,

E10. Unwilling to maintain food habits and current physical activity for the whole study duration,

E11. With a personal history of anorexia nervosa, bulimia or significant eating disorders according to the investigator,

E12. Having a lifestyle deemed incompatible with the study according to the investigator including drug and alcohol abuse,

E13. Taking part in another clinical trial or being in the exclusion period of a previous clinical trial,

E14. Under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision,

E15. Presenting a psychological or linguistic incapability to sign the informed consent,

E16. Impossible to contact in case of emergency.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sonia Brinet; +33 (0)2 40 20 57 99; sonia.brinet@biofortis.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT05133076
• Other Study ID Numbers: PEC19156
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: BioGaia Pharma AB
• Original Responsible Party: Same as current
• Current Study Sponsor: BioGaia Pharma AB
• Original Study Sponsor: Same as current
• Collaborators: BioFortis

Investigators

• Study Director: Petra J Lierud; BioGaia Pharma

• PRS Account: BioGaia Pharma AB
• Verification Date: February 2023