Clinical trial NCT04321460: Study of LRG-002 Hard Capsules (Lek d.d., Slovenia) Used in the Prophylaxis of Antibiotic-associated Diarrhea in Adults.
Official title: Multicentre, Double-blind, Randomized, Placebo-controlled, Parallel-group Efficacy and Safety Study of LRG-002 Hard Capsules (Lek d.d., Slovenia) Used in the Prophylaxis of Antibiotic-associated Diarrhea in Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Antibiotic-associated Diarrhea
Keywords: diarrhea
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
First posted: 2020-03-25
Enrollment: 520
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study was to investigate the efficacy and safety of LRG-002 investigational medicinal product, capsules (Lek d.d., Slovenia) in comparison with placebo, as an adjunct treatment for prophylaxis of antibiotic-associated diarrhea (AAD) in patients with acute respiratory diseases (ARDs) receiving a standard antimicrobial therapy.

Detailed description: This study was the prospective, multi-centered, double-blinded, randomized, parallel-group clinical study. The study investigated the efficacy and safety of LRG-002 investigational medicinal product, capsules (Lek d.d., Slovenia) in comparison with placebo, as an adjunct treatment for prophylaxis of antibiotic-associated diarrhea (AAD) in patients with acute respiratory diseases (ARDs) receiving a standard antimicrobial therapy.

The study comprised the following periods:

Study Periods Visit 1 (Day 1): Screening + randomization + initiation of treatment

Patients started participating in the study after signing the Informed Consent Form. Having completed screening tests, eligible patients were randomized on the same day to receive either LRG-002 or matching placebo capsules, each as an adjunct to the prescribed antibiotic. The treatment group was determined by randomization at a center ratio. Study subjects were supplied with the patient diary and blinded investigational product (investigational medicinal product or placebo) depending on the assigned treatment group. Patients could start study treatment only after receiving appropriate training. On Day 1, the study started in both groups from randomization and administration of the first dose of the investigational product depending on the assigned group after randomization:

Group T, treated with LRG-002: a single dose of 1 oral hard capsule taken during meals with some water; the product was to be taken orally 2 times per day for 14 days.

Group R, provided with placebo:a single dose of 1 oral hard capsule taken during meals with some water; the product is to be taken orally 2 times per day for 14 days.

Visit 2 (Day 7): Intermediate Follow-up Visit

Visit 3 (Day 15) : Visit 3 was scheduled at Day 15 when a patient was to come to the study site bringing along the completed diary, unused laboratory kit, unused product and empty packages.

Eligibility criteria: Patients will be considered eligible for study participation if they meet the following inclusion criteria:

1. An Informed Consent Form for study participation voluntarily signed by a patient;
2. Male and female subjects, 18 to 65 years of age inclusive;
3. Antibacterial treatment for active ARDs started/to be started on the first day of the study (7-day course of oral beta-lactam antibiotic). Only one AB should be used per subject, in an outpatient setting. Diagnostic procedures of ARD and the prescription of antibiotic therapy should be completed before signing of the Informed Consent Form.
4. Female patients will be considered as eligible for study participation if they are: Unable to become pregnant or Capable of childbirth, but with negative pregnancy test at the screening visit, and the patient agrees to continuously and properly use one a following suitable methods of contraception Male participants,. together with their partner, are to use appropriate contraception during the entire study period starting from signing of the Informed Consent Form and until the study end, and for 30 days after study completion;

6. The ability to understand the information about the clinical study, readiness to comply with the study protocol requirements, ability to take the investigational products and evaluate symptoms on his (or her) own using diary/questionnaires as per protocol; 7. Ability to maintain the habitual lifestyle throughout the study, including diet. 8. Willing not to consume any products containing probiotics during participation in the clinical trial. 9. Willing not to take part in any other study during the present trial.

Patients will not be eligible for study enrollment if they have one or more of the following criteria:

1. Any therapy (including medications, medical devices and dietary supplements) that can influence the stool consistency, according to the Investigator's opinion, should not be used within 14 days prior to Visit 1;
2. Use of immunosuppressive, immunostimulating and immunomodulating agents including drugs of herbal origin and dietary supplements within 30 days prior to the study start;
3. Use of anti-rejection medication after stem cell or solid organ transplant;
4. Use of systemic glucocorticosteroids within 8 weeks prior to the study start;
5. Use of proton pump inhibitors within 3 months prior to Visit 1;
6. Chemotherapy or radiation;
7. History of recurrent diarrhea;
8. Patient has diarrhea or loose stool within 2 days prior to the study start;
9. Patient has severe ARD expected to require an administration of antibiotics therapy for more than 7 days or prescription of additional antibiotics;
10. Use of antimicrobials within 3 months prior to the study start;
11. Use of yeast/probiotic/fermented products within 2 weeks prior to the first visit;
12. Known allergy/hypersensitivity to the investigational medicinal product in the medical history;
13. Immunocompromised patients;
14. Known digestion/absorption disorders of the gastrointestinal tract (e.g. inflammatory bowel disease, celiacia, pancreatitis, motility disorders etc.) and/or gastrointestinal surgery;
15. Known irritable bowel syndrome;
16. Known small intestinal bacterial overgrowth;
17. Patient has pyrexia of more than 38°C;
18. Pregnant and/or breastfeeding women;
19. Participation in other clinical trials of medicinal products or medical devices at the screening Visit or within 30 days before the screening Visit;
20. Surgical intervention within 30 days before the screening visit or planned surgical treatment during the trial (before a follow-up visit is completed), including diagnostic procedures or inpatient stay;
21. Known or suspected alcohol and/or drug addiction;
22. A suspected low compliance or incapability of the patient to perform the procedures and comply with restrictions according to the trial protocol (e.g., due to mental disorders);
23. Potential for translocation of probiotic across bowel wall (Presence of an active bowel leak, acute abdomen, active intestinal disease including colitis, or significant bowel dysfunction; presence of neutropenia or anticipation of neutropenia after chemotherapy; radiation therapy);
24. Any disorders of cardiovascular, renal, hepatic, gastrointestinal, endocrine and nervous systems, or other conditions/diseases which, in the Investigator's opinion, may render study participation unsafe for a patient or may affect a test result.

Primary outcomes:
measure: Number of Participants With the Occurrence of Antibiotic-associated Diarrhea (AAD) - Per Protocol (PP) Population
timeFrame: 14 days
measure: Number of Participants With the Occurrence of Antibiotic-associated Diarrhea (AAD) - Intention to Treat (ITT) Population
timeFrame: 14 days
Secondary outcomes:
measure: Mean Number of Bowel Movements Per Day
timeFrame: 14 days
measure: Number of Participants With the Occurrence of Any Diarrhea
timeFrame: 14 days
measure: Number of Participants With the Occurrence of C. Difficile-associated Antibiotic-associated Diarrhea (AAD)
timeFrame: 14 Days
measure: Number of Participants With the Occurrence of Non-C. Difficile-associated AAD
timeFrame: 14 Days
measure: Mean Duration of Antibiotic-associated Diarrhea (AAD)
timeFrame: 14 days
measure: Mean Duration of Any Diarrhea
timeFrame: 14 days
measure: Change in Stool Consistency
timeFrame: Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14
measure: Number of Gastrointestinal Symptoms by Severity
timeFrame: 14 days
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Day 15
measure: Number of Participants Hospitalized
timeFrame: 14 days
measure: Number of Participants Using Standard Symptomatic Therapy
timeFrame: 14 days
measure: Number of Days of Using Standard Symptomatic Therapy
timeFrame: 14 days
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Sandoz Investigative Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Sandoz Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Sandoz Investigative Site
Study officials:
References: