Clinical trial NCT05133076: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Opioid-Induced Constipation
Lead sponsor: BioGaia Pharma AB
Sponsor class: INDUSTRY
Collaborators: name: BioFortis
First posted: 2021-11-24
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change in the average weekly number of Spontaneous Bowel Movements (SBMs) (expressed in number of stools/week)
timeFrame: Over the 4 week treatment period
Secondary outcomes:
measure: 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
timeFrame: Average over the last two weeks of treatment
measure: Change in the average weekly number of BMs (Bowel Movements)
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Change in the average weekly number of CSBMs (Complete Spontaneous Bowel Movement)
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Change in the average weekly number of SBMs
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Change in the average weekly number of SBMs with no straining (straining score 1)
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Time to first SBM and CSBM after the last recorded stool before the randomisation
timeFrame: Over 4 week treatment period
measure: Change in the number of days with presence of SBMs
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Change in the number of days with presence of CSBMs
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Change in the average weekly number of SBMs rated 3 or 4 on the BSS (Bristol Stool Scale)
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Change of stool consistency assessed by the BSS (Bristol Stool Scale)
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Change of the overall BFI (Bowel Function Index) score
timeFrame: Over 4 week treatment period
measure: Change in the average daily abdominal bloating score
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Change in the average daily abdominal discomfort score
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Change in average daily pain at defecation assessed by the Visual Analogic Scale for pain at defecation (VAS)
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Change in the weekly frequency of rescue laxative use assessed by the daily diary
timeFrame: Over 4 week treatment period; during each week of the treatment period; and up to 8 weeks at study completion.
measure: Frequency of rescue laxative use assessed by the daily diary.
timeFrame: Over the 4 week treatment period
measure: General health state measuring vital parameters assessed - Body weight
timeFrame: Through study completion, 10 weeks
measure: General health state measuring vital parameters assessed- Diastolic Blood Pressure
timeFrame: Through study completion, 10 weeks
measure: General health state measuring vital parameters assessed- Systolic Blood Pressure
timeFrame: Through study completion, 10 weeks
measure: General health state measuring vital parameters assessed- Vital signs
timeFrame: Through study completion, 10 weeks
measure: the frequency of adverse events (AE), serious adverse events (SAE), Treatment-Emergent Adverse events (TEAE), Serious treatment-emergent adverse events (STEAE)
timeFrame: Through study completion, 10 weeks
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens
city: Saint- Herblain
country: France
facility: CHU DE NANTES (Hôpital Nord Laennec)
city: Valenciennes
country: France
facility: CH de Valenciennes
Study officials:
affiliation: BioGaia Pharma
name: Petra J Lierud
role: STUDY_DIRECTOR
References: