Clostridium Difficile Infection
Conditions
Keywords
Clostridioides difficile, CDAD (Clostridioides difficile-associated diarrhea), DNA polymerase IIIC
Brief summary
Segments 2A and 2B of this trial evaluate the safety, efficacy, pharmacokinetics, fecal concentrations, and fecal microbiome effects of ACX-362E \[ibezapolstat\] in patients with C. difficile infection (CDI).
Detailed description
This Phase 2, multicenter, open-label single-arm segment (2A) followed by a double-blind, randomized, active-controlled segment (2B) is designed to evaluate ACX-362E in the treatment of CDI. Segment 2A of this trial was an open-label study of up to 20 patients at 6 study centers and was terminated early at 10 patients based on the protocol-specified Trial Oversight Committee's assessment of the compelling efficacy and safety data. Patients were treated with 450 mg of oral ibezapolstat twice daily for 10 days. The trial will advance to Segment 2B which is a double-blind comparison of ibezapolstat to the standard of care, oral vancomycin, in approximately 64 subjects (1-1 randomization) at up to approximately 15 sites. Subjects will be evaluated for cure, safety, and tolerability. All subjects in both segments will have stool samples tested for microbiome profiles. Pharmacokinetic (PK) testing for systemic exposure will be performed on blood samples. Stool samples will be tested for study drug concentration.
Interventions
DRUGIbezapolstat
Investigational antibacterial agent
DRUGVancomycin
Active comparator
Sponsors
Acurx Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Vancomycin capsules will be over-encapsulated to have identical appearance to ibezapolstat capsules. Placebo capsules will be used to enable a double-dummy, double-blind design.
Intervention model description
In Segment 2B, approximately 64 patients will be randomly assigned in a 1:1 fashion to ibezapolstat or the standard of care positive control, vancomycin.
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female 18 to 90 years of age, inclusive, at the time of Screening. 2. Capable of reading, understanding, and signing the written informed consent; able to adhere to all study procedures and attend all scheduled study visits. 3. Confirmed diagnosis of mild or moderate CDI as defined by the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America guidelines (McDonald et al. 2018). Subjects will be diagnosed with CDI based on clinical and laboratory findings: 1. The presence of diarrhea, defined as passage of ≥ 3 UBMs within 24 hours before dosing; an unformed stool is defined as a Type 5, 6, or 7 on the Bristol Stool Chart (Appendix 2) 2. A stool test result positive for the presence of C. difficile free toxins using tests that detect toxin A/B (and it is prospectively agreed with the Sponsor). The Sponsor will provide a toxin A/B test kit if the site does not have it as part of standard of care test. 3. Mild or moderate CDI as defined as a white blood cell count of ≤ 15000 cells/mL and a serum creatinine level \< 1.5 mg/dL.
Exclusion criteria
1. Received more than 24 hours of dosing (\> 4 doses) of oral vancomycin for the current episode of CDI before first dose of study drug. 2. Received more than 24 hours of dosing (\> 2 doses) of oral fidaxomicin for the current episode of CDI before first dose of study drug. 3. Received more than 24 hours of dosing (\> 3 doses) of oral/IV metronidazole for the current episode of CDI before first dose of study drug. 4. Received any other antibacterial therapy for the current CDI episode within 48 hours before the first dose of study drug. 5. Subjects considered treatment failures on prior antibiotics for their current episode of CDI will be excluded. 6. More than 3 episodes of CDI in the previous 12 months or more than 1 prior episode in the last 3 months, excluding the current episode. 7. Severe, complicated, or life-threatening fulminant CDI with evidence of hypotension (systolic blood pressure less than 90 mmHg), septic shock, peritoneal signs or ileus, or toxic megacolon. 8. Elevated liver transaminases (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\]) greater than 2 times ULN. 9. Active inflammatory bowel disease (Crohn's disease, ulcerative colitis, Irritable Bowel Syndrome with chronic diarrhea). 10. Any other non-C. difficile diarrhea. 11. Active gastroenteritis because of Salmonella, Shigella, Escherichia coli 0157H7, Yersinia or Campylobacter, a parasite, or virus within the past 2 weeks. 12. Had a known positive diagnostic test for other relevant gastrointestinal \[GI\] pathogens in the 2 weeks before study drug treatment and/or colonization/infection by ova or parasites. 13. Major GI surgery (ie, significant bowel resection) within 3 months of enrollment (does not include appendectomy or cholecystectomy). 14. Prior or current use of anti-C. difficile toxin antibodies. 15. Have received a vaccine against C. difficile or its toxins. 16. Anticipated that systemic antibacterial therapy for a non-CDI infection will be required for \> 7 days after start of study therapy. 17. Actively taking anti-diarrheals, and unable to discontinue anti-diarrheal medication, or any medication with the potential to slow bowel movement (for opiates, a stable dose, including use as needed, is permitted). 18. Actively taking Saccharomyces boulardii and unwilling to discontinue during the study period. 19. Received a fecal transplant in the previous 3 months. 20. Received laxatives in the last 48 hours. 21. Unable or unwilling to stop taking oral probiotics for the duration of the study. 22. Received intravenous immunoglobulin within 3 months before study drug treatment. 23. Sepsis. 24. Have a known current history of significantly compromised immune system such as: 1. Subjects with a known history of human immunodeficiency virus infection and CD4 \<200 cells/mm3 within 6 months of start of study therapy. 2. Severe neutropenia with neutrophil count \< 500 cells/mL. 3. Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy. 25. Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Segment 2A: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population | 12 days | Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart. |
| Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | 12 days | Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart. |
| Segment 2B Per Protocol (PP) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | 12 days | Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Segment 2B Per Protocol (PP) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | 38 days | Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile. |
| Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Days -2, 3, 5, 8,10,12, 20, 30, and 38 | Fecal ibezapolstat concentrations were measured for specified days following dose administration. Specified days were 3, 5, 8, 10, 12, and 20. Amount listed as zero not included in determination of Geometric Mean and CV%. |
| Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | 38 days | Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile. |
| Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Days 1, 5, and 10: 2 and 4 hours post-dose | Plasma ibezapolstat concentrations were measured at specified day and time points following dose administration. Amount listed as zero not included in determination of Geometric Mean and CV%. |
| Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Days 1 and 5: 2 and 4 hours post-dose | Plasma ibezapolstat concentrations were measured at specified day and time points following dose administration. Amount listed as zero not included in determination of Geometric Mean and CV% |
| Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Days -2, 3, 5, 8,10, 12, 20, 30, and 38 | Fecal ibezapolstat concentrations were measured for specified days following dose administration. Specified days were 3, 5, 8, 10, 12, 20, and 38. Amount listed as zero not included in determination of Geometric Mean and CV%. |
| Segment 2A: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population | 38 days | Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI) | 56 days after end of treatment (Day 66) and 84 days after end of treatment (Day 94) | Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 56 days \[day 66\] or within 84 days \[day 94\]. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile. |
| Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores | Days 12, 38, 66, and 94 | Change from baseline in each of the 5 dimensions of the EQ-5D-5L score, each scored on a scale of 1-5, with 1 being normal and 5 indicating extreme difficulty or impairment. The 5 dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Summary Index Scores (the 5 dimensions combined into a single value) are reported here. Values for the index score ranges from -0.59 to 1, where 1 is the best possible health state. |
| Segment 2A: Microbiome Effects | Days 10 and 40 | The Shannon Diversity Index and Inverse Simpson Diversity Index are used to quantify biodiversity in a community like the gut microbiome, measuring how many different species are present in a community (richness) and how close in numbers different species in the community are to each other (evenness). The Shannon considers both factors while the Inverse Simpson focuses on evenness. The Shannon diversity index is calculated using natural logarithms, and units cancel out in the calculation, so it lacks units. It ranges from 0 to infinity. The Inverse Simpson represents the likelihood of selecting two different individuals from a population. It is a ratio and has no units. It ranges from 0 to 1. For both indexes, higher values indicate greater diversity. |
| Segment 2A: Time to Resolution of Diarrhea | 10 days | Time in days from outset of treatment to the first formed bowel movement not followed within the next 24 hours by an unformed bowel movement (UBM), defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart. |
| Segment 2B: Time to Resolution of Diarrhea | 40 days | Time in days from outset of treatment to the first formed bowel movement not followed within the next 24 hours by an unformed bowel movement (UBM), defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart. |
Countries
United States
Participant flow
Recruitment details
Segment 2A, Ibezapolstat Open-Label Arm: 14 enrolled. Segment 2B, Vancomycin-Controlled Double-Blind: 39 enrolled.
Pre-assignment details
Segment 2A: 4 participants failed screening. 10 participants proceeded to treatment. Segment 2A participants did not participate in Segment 2B. Segment 2B: 7 participants failed screening. 32 participants proceeded to randomization and treatment. Segment 2B did not include Segment 2A participants.
Participants by arm
| Arm | Count |
|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm Participants with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally (3 x 150 mg capsules) every 12 hours for 10 days. Study drug was administered with 240 mL water. Participants were followed for recurrence for 28±2 days, regardless of response to ibezapolstat. Safety, tolerability, and efficacy were assessed by the Trial Oversight Committee which then recommended early termination of this segment of the trial and advancement to the 2B Segment because the first 10 patients demonstrated clinical cure. | 10 |
| Segment 2B: Ibezapolstat Arm--Double-blind, Randomized, Active-controlled Clinical Segment Participants with diarrhea caused by C. difficile who were randomized to this arm received 450 mg ibezapolstat (3 x 150 mg capsules) every 12 hours for 10 days with placebo every 12 hours for 10 days (to maintain blind). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation. | 18 |
| Segment 2B: Vancomycin Arm--Double-blind, Randomized, Active-controlled Clinical Segment Participants with diarrhea caused by C. difficile who were randomized to this arm received vancomycin every 6 hours (1 capsule 125 mg + 2 placebo capsules every 12 hours or 1 capsule 125 mg every 12 hours). Participants were followed for 28±2 days for recurrence. Blinding was maintained by over-encapsulation. | 14 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 2B: Double-Blind Active-Controlled | Did not receive study drug | 0 | 1 | 0 |
| 2B: Double-Blind Active-Controlled | Treatment completed but incorrectly recorded as discountinued. | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Total | Segment 2B: Ibezapolstat Arm--Double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B: Vancomycin Arm--Double-blind, Randomized, Active-controlled Clinical Segment |
|---|---|---|---|---|
| Age, Continuous Segment 2A | 49.5 years | 49.5 years | — | — |
| Age, Continuous Segment 2B | — | 59.4 years | 63.2 years | 61.8 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 31 Participants | 12 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 11 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 41 Participants | 18 Participants | 13 Participants |
| Sex: Female, Male Female | 5 Participants | 31 Participants | 15 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 17 | 0 / 14 |
| other Total, other adverse events | 4 / 10 | 6 / 17 | 2 / 14 |
| serious Total, serious adverse events | 0 / 10 | 1 / 17 | 0 / 14 |
Outcome results
Primary
Segment 2A: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population
Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Time frame: 12 days
Population: 10 participants were analyzed in the modified Intent-to-Treat (mITT) and Per Protocol (PP) populations. The mITT population includes all subjects who were treated and assessed at the TOC visit. The PP population consists of patients in the mITT population with no major protocol deviations.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population | CC at TOC, yes | 10 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population | CC at TOC, no | 0 Participants |
Primary
Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)
Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Time frame: 12 days
Population: ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | CC at TOC, yes | 15 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | CC at TOC missing | 1 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | CC at TOC, no | 2 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | CC at TOC, yes | 14 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | CC at TOC missing | 0 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Intent-to-Treat (ITT) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | CC at TOC, no | 0 Participants |
Primary
Segment 2B Per Protocol (PP) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI)
Percentage of patients with CC at the test of cure (TOC) visit on day 12. CC was defined as survival and the resolution of diarrhea in the 24-hour period immediately before end of treatment (EOT--day 10) that was maintained for 48 hours post EOT without a requirement for additional CDI treatment. Diarrhea was defined as 3 or more unformed bowel movements (UBMs) in a 24-hour period; fewer than 3 UBMs was considered as resolution of diarrhea. A UBM was defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Time frame: 12 days
Population: PP participants were those in the ITT population who had no major protocol deviations. The ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Per Protocol (PP) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | CC at TOC, yes | 15 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Per Protocol (PP) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | CC at TOC, no | 1 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Per Protocol (PP) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | CC at TOC, yes | 14 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Per Protocol (PP) Population: Clinical Cure (CC) of Clostridioides Difficile Infection (CDI) | CC at TOC, no | 0 Participants |
Secondary
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Fecal ibezapolstat concentrations were measured for specified days following dose administration. Specified days were 3, 5, 8, 10, 12, 20, and 38. Amount listed as zero not included in determination of Geometric Mean and CV%.
Time frame: Days -2, 3, 5, 8,10, 12, 20, 30, and 38
Population: Participants with undetectable concentrations were not included in the data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day -2 | NA µg/g | — |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 3 | 285.88 µg/g | Geometric Coefficient of Variation 1058 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 5 | 532.96 µg/g | Geometric Coefficient of Variation 1034 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 8 | 943.87 µg/g | Geometric Coefficient of Variation 410 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 10 | 1565.77 µg/g | Geometric Coefficient of Variation 271 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 12 | 264.47 µg/g | Geometric Coefficient of Variation 1001 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 20 | 53.52 µg/g | Geometric Coefficient of Variation 18317 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 30 | NA µg/g | — |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 38 | 267.73 µg/g | Geometric Coefficient of Variation 24 |
Secondary
Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Plasma ibezapolstat concentrations were measured at specified day and time points following dose administration. Amount listed as zero not included in determination of Geometric Mean and CV%.
Time frame: Days 1, 5, and 10: 2 and 4 hours post-dose
Population: 3 participants from the original population did not have plasma samples taken and were not included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Day 1 Hour 2 | 114.32 ng/mL | Geometric Coefficient of Variation 249 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Day 1 Hour 4 | 305.94 ng/mL | Geometric Coefficient of Variation 171 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Day 5 Hour 2 | 185.37 ng/mL | Geometric Coefficient of Variation 244 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Day 5 Hour 4 | 472.54 ng/mL | Geometric Coefficient of Variation 48 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Day 10 Hour 2 | 152.02 ng/mL | Geometric Coefficient of Variation 227 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Day 10 Hour 4 | 527.10 ng/mL | Geometric Coefficient of Variation 51.9 |
Secondary
Segment 2A: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population
Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Time frame: 38 days
Population: 10 participants were analyzed in the modified Intent-to-Treat (mITT) and Per Protocol (PP) populations. The mITT population includes all subjects who were treated and assessed at the TOC visit. The PP population consists of patients in the mITT population with no major protocol deviations.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population | SCC, yes | 10 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) Per Protocol (PP)/Modified Intent-to-Treat (mITT) Population | SCC, no | 0 Participants |
Secondary
Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)
Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Time frame: 38 days
Population: ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | SCC, yes | 15 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | SCC missing | 1 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | SCC, no | 2 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | SCC, yes | 12 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | SCC missing | 0 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Intent-to-Treat (ITT) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | SCC, no | 2 Participants |
Secondary
Segment 2B Per Protocol (PP) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI)
Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 28 days. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Time frame: 38 days
Population: PP participants were those in the ITT population who had no major protocol deviations. The ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Per Protocol (PP) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | SCC, yes | 15 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Per Protocol (PP) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | SCC, no | 1 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Per Protocol (PP) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | SCC, yes | 12 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Per Protocol (PP) Population: Sustained Clinical Cure (SCC) of Clostridioides Difficile Infection (CDI) | SCC, no | 2 Participants |
Secondary
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations
Fecal ibezapolstat concentrations were measured for specified days following dose administration. Specified days were 3, 5, 8, 10, 12, and 20. Amount listed as zero not included in determination of Geometric Mean and CV%.
Time frame: Days -2, 3, 5, 8,10,12, 20, 30, and 38
Population: Participants with undetectable concentrations were not included in the data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day -2 | NA µg/g | — |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 3 | 411.4 µg/g | Geometric Coefficient of Variation 151 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 5 | 407.65 µg/g | Geometric Coefficient of Variation 217 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 8 | 716.21 µg/g | Geometric Coefficient of Variation 148 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 10 | 958.15 µg/g | Geometric Coefficient of Variation 169 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 12 | 250.52 µg/g | Geometric Coefficient of Variation 63.1 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 20 | 12.74 µg/g | Geometric Coefficient of Variation 91.2 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 30 | NA µg/g | — |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Fecal Concentrations | Day 38 | NA µg/g | — |
Secondary
Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations
Plasma ibezapolstat concentrations were measured at specified day and time points following dose administration. Amount listed as zero not included in determination of Geometric Mean and CV%
Time frame: Days 1 and 5: 2 and 4 hours post-dose
Population: 3 participants from the original population did not have plasma samples taken and were not included. 1 participant from the original population did not receive the study drug and was not included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Day 1 Hour 2 | 454.82 ng/mL | Geometric Coefficient of Variation 178 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Day 1 Hour 4 | 268.07 ng/mL | Geometric Coefficient of Variation 128 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Day 5 Hour 2 | 441.39 ng/mL | Geometric Coefficient of Variation 206 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Pharmacokinetics and Systemic Exposure to Ibezapolstat (ACX-362E), Plasma Concentrations | Day 5 Hour 4 | 358.52 ng/mL | Geometric Coefficient of Variation 151 |
Other Pre-specified
Segment 2A: Microbiome Effects
The Shannon Diversity Index and Inverse Simpson Diversity Index are used to quantify biodiversity in a community like the gut microbiome, measuring how many different species are present in a community (richness) and how close in numbers different species in the community are to each other (evenness). The Shannon considers both factors while the Inverse Simpson focuses on evenness. The Shannon diversity index is calculated using natural logarithms, and units cancel out in the calculation, so it lacks units. It ranges from 0 to infinity. The Inverse Simpson represents the likelihood of selecting two different individuals from a population. It is a ratio and has no units. It ranges from 0 to 1. For both indexes, higher values indicate greater diversity.
Time frame: Days 10 and 40
Population: 8 of the 10 participants in Segment 2A provided stool samples and were analyzed. Not all 8 subjects were able to provide samples for all time points, so the data are not continuous. Data is reported as mean increase in biodiversity from the baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Microbiome Effects | Change from Baseline on Inverse Simpson Index, during treatment (until Day 10) | 0.14 Index | Standard Deviation 0.06 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Microbiome Effects | Change from Baseline on Inverse Simpson Index, after treatment (until Day 40) | 0.22 Index | Standard Deviation 0.1 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Microbiome Effects | Change from Baseline on Shannon Diversity Index, during treatment (until Day 10) | 0.98 Index | Standard Deviation 0.48 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Microbiome Effects | Change from Baseline on Shannon Diversity Index, after treatment (until Day 40) | 1.7 Index | Standard Deviation 0.87 |
Other Pre-specified
Segment 2A: Time to Resolution of Diarrhea
Time in days from outset of treatment to the first formed bowel movement not followed within the next 24 hours by an unformed bowel movement (UBM), defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Time frame: 10 days
Population: 10 participants were analyzed in the modified Intent-to-Treat (mITT) and Per Protocol (PP) populations. The mITT population includes all subjects who were treated and assessed at the TOC visit. The PP population consists of patients in the mITT population with no major protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2A: Time to Resolution of Diarrhea | 5 Days to resolution of diarrhea |
Other Pre-specified
Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI)
Clinical cure (CC) at the test of cure (TOC) visit (ie, at least 48 hours after end of treatment \[day 10\]) and no recurrence within 56 days \[day 66\] or within 84 days \[day 94\]. Recurrence was defined as a new episode of diarrhea (3 or more UBMs in a 24-hour period) with a positive toxin result, using a Sponsor-approved C. difficile free toxin test and, in the opinion of the Investigator, requiring retreatment with an antibacterial agent for C. difficile.
Time frame: 56 days after end of treatment (Day 66) and 84 days after end of treatment (Day 94)
Population: Participants from the ITT population were recruited for an extended follow-up period. In the ITT extension population, 1 ibezapolstat subject failed at the CC (Day 12) and 1 vancomycin subject failed at the SCC (Day 38); both failures carried forward to both ECC evaluations. There were no failures post SCC (Day 38). In the ITT extension population who achieved a SCC, 5/5 ibezapolstat-treated participants and 7/7 vancomycin-treated participants experienced no infection recurrence.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI) | Extended Clinical Cure 56 days after End of Treatment (Day 66) | yes | 5 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI) | Extended Clinical Cure 56 days after End of Treatment (Day 66) | no | 1 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI) | Extended Clinical Cure 84 days after End of Treatment (Day 94) | yes | 5 Participants |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI) | Extended Clinical Cure 84 days after End of Treatment (Day 94) | no | 1 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI) | Extended Clinical Cure 84 days after End of Treatment (Day 94) | no | 1 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI) | Extended Clinical Cure 56 days after End of Treatment (Day 66) | yes | 7 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI) | Extended Clinical Cure 84 days after End of Treatment (Day 94) | yes | 7 Participants |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Intent-to-Treat (ITT) Extension Population: Extended Clinical Cure (ECC) of Clostridioides Difficile Infection (CDI) | Extended Clinical Cure 56 days after End of Treatment (Day 66) | no | 1 Participants |
Other Pre-specified
Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores
Change from baseline in each of the 5 dimensions of the EQ-5D-5L score, each scored on a scale of 1-5, with 1 being normal and 5 indicating extreme difficulty or impairment. The 5 dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Summary Index Scores (the 5 dimensions combined into a single value) are reported here. Values for the index score ranges from -0.59 to 1, where 1 is the best possible health state.
Time frame: Days 12, 38, 66, and 94
Population: PP participants were those in the intent-to-treat (ITT) population who had no major protocol deviations. The ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores | Day 12 | 0.1667 Summary Index Score | Standard Deviation 0.1226 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores | Day 38 | 0.1908 Summary Index Score | Standard Deviation 0.1379 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores | Day 66 | 0.2677 Summary Index Score | Standard Deviation 0.1649 |
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores | Day 94 | 0.2677 Summary Index Score | Standard Deviation 0.1649 |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores | Day 94 | 0.2004 Summary Index Score | Standard Deviation 0.1158 |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores | Day 12 | 0.1611 Summary Index Score | Standard Deviation 0.1203 |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores | Day 66 | 0.1964 Summary Index Score | Standard Deviation 0.1124 |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B Per Protocol (PP) Population: Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Quality of Life Scores | Day 38 | 0.1897 Summary Index Score | Standard Deviation 0.1506 |
Other Pre-specified
Segment 2B: Time to Resolution of Diarrhea
Time in days from outset of treatment to the first formed bowel movement not followed within the next 24 hours by an unformed bowel movement (UBM), defined as a Type 5, 6, or 7 bowel movement on the Bristol Stool Chart.
Time frame: 40 days
Population: The Per Protocol (PP) population is represented here. PP participants were those in the intention-to-treat (ITT) population who had no major protocol deviations. The ITT population is defined as all randomized subjects, analyzed according to their randomized treatment assignment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Segment 2A: Ibezapolstat (ACX-362E) Open-Label Single-Arm | Segment 2B: Time to Resolution of Diarrhea | 8 Days to resolution of diarrhea |
| Segment 2B: Vancomycin Arm--double-blind, Randomized, Active-controlled Clinical Segment | Segment 2B: Time to Resolution of Diarrhea | 9 Days to resolution of diarrhea |