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NCT01597505

Study of CB-183,315 in Participants With Clostridium Difficile Associated Diarrhea (MK-4261-005)

Completed Phase 3 Results posted Last updated 23 July 2019
What this trial tests

Phase 3 trial testing Surotomycin in Clostridium Difficile Infection in 606 participants. Completed in 20 March 2015.

Timeline
16 May 2012
Primary endpoint
20 March 2015
20 March 2015

Quick facts

Lead sponsorCubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment606
Start date16 May 2012
Primary completion20 March 2015
Estimated completion20 March 2015

Drugs / interventions tested

Conditions studied

Sponsor

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) — full company profile →

Who can join

Adults 18 to 90, any sex, with Clostridium Difficile Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Adjusted Percentage of Participants With a Clinical Outcome of Cure at the End of Treatment (EOT) Primary · Up to 13 days

A clinical outcome of cure at EOT was determined by resolution of diarrhea, defined as ≤ 2 loose stools per 24-hour period for at least 2 consecutive days and the lack of need for additional antibiotics to treat the current CDAD episode after completion of the study treatment period. Participants requiring a collection device were considered to have resolution of diarrhea when the volume of stool (over a 24-hour period) was decreased by 75% as compared to baseline or the participant was no longer passing liquid stool. The estimated adjusted percentage was a weighted average across all strata,

GroupValue95% CI
Surotomycin79.073.9 – 83.2
Vancomycin83.678.8 – 87.4
Number of Participants With Clinical Response Over Time Secondary · Up to Day 41

Clinical response over time as measured by those without treatment failure, recurrence, death, or lost to follow-up, measured as the number of participants without failure events (survivors) through the end of therapy (reported for Day 14) and from end of therapy to Day 40 (reported for Day 41).

Day 14
GroupValue95% CI
Surotomycin227
Vancomycin231
Day 41
GroupValue95% CI
Surotomycin147
Vancomycin151
Adjusted Percentage of Participants With Sustained Clinical Response at the End of Study Secondary · Up to Day 50

Sustained clinical response at the end of study was achieved by participants who had a clinical outcome of cure at the end of treatment (Days 40-50) and did not experience a recurrence of CDAD, did not die, were not lost to follow-up, and did not have end of study visit prior to Day 40. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.

GroupValue95% CI
Surotomycin60.655.0 – 66.0
Vancomycin61.455.9 – 66.8
Percentage of Participants With at Least One Adverse Event (AE) Primary · Up to Day 50

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. AEs may be new events or may be pre-existing conditions that have become aggravated or have worsened in severity or frequency; or may be clinically significant changes from baseline in physic

GroupValue95% CI
Surotomycin48.5
Vancomycin55.2
Percentage of Participants With at Least One Serious Adverse Event (SAE) Primary · Up to Day 50

A SAE is any adverse experience occurring at any dose that results in any of the following outcomes: death; a life-threatening experience, referring to a situation in which the participant was at risk of death at the time of the event, requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; or is considered to be an important medical event.

GroupValue95% CI
Surotomycin14.4
Vancomycin12.9
Percentage of Participants Who Discontinued Treatment Due to an AE Primary · Up to Day 13

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. AEs may be new events or may be pre-existing conditions that have become aggravated or have worsened in severity or frequency; or may be clinically significant changes from baseline in physic

GroupValue95% CI
Surotomycin5.6
Vancomycin2.8
Adjusted Percentage of Participants With Sustained Clinical Response at Day 24 Secondary · Day 24

Sustained clinical response at Day 24 was defined as participants who had a clinical outcome of cure at Day 24, who did not experience a recurrence of CDAD, did not die, were not lost to follow-up. Only the first failure event was counted per participant. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.

GroupValue95% CI
Surotomycin66.661.1 – 71.8
Vancomycin66.160.5 – 71.3
Adjusted Percentage of Participants With Recurrence of CDAD at End of Study Secondary · Up to Day 50

Participants with recurrences were defined as those who were cured at the end of therapy and had a recurrence or were lost to follow-up, died or had a Day 40 -50 contact prior to Day 40. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.

GroupValue95% CI
Surotomycin17.713.8 – 22.4
Vancomycin21.216.9 – 26.1
Time to Resolution of Diarrhea Secondary · Up to Day 13

Time to resolution of diarrhea with =\< 2 unformed bowel movements (UBM) per 24-hour period was calculated as the date/time of last UBM minus the date/time of the first dose of study drug.

GroupValue95% CI
Surotomycin2.82.2 – 3.3
Vancomycin3.02.2 – 3.3
Time to Reappearance of Diarrhea From End of Treatment to the End of Study Secondary · Up to Day 50

Time to reappearance of diarrhea with \>= 3 UBM per 24-hour period was calculated as the last date/time of study drug dose to the date/time of first reappearance of 3 or more UBMs among participants who were cured at end of treatment.

GroupValue95% CI
SurotomycinNANA – NA
VancomycinNANA – NA
Adjusted Percentage of Participants With a Clinical Response at the End of Treatment for Infections Deemed to be Caused by the C. Difficile BI/NAP1/027 Strain at Baseline Secondary · Up to Day 13

Clinical response corresponded to a clinical outcome of cure at the end of treatment, and was achieved by participants with infections deemed to be caused by the C. difficile BI/NAP1/027 strain at baseline, who did not fail treatment, did not die, or were not lost to follow-up at the end of treatment. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.

GroupValue95% CI
Surotomycin88.575.8 – 92.4
Vancomycin86.376.2 – 92.6
Adjusted Percentage of Participants Per Protocol 1 Population With a Clinical Response at the End of Treatment Secondary · Up to Day 13

Clinical response corresponded to a clinical outcome of cure at the end of treatment, and was achieved by participants who did not fail treatment, did not die, or were not lost to follow-up at the end of treatment. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.

GroupValue95% CI
Surotomycin89.184.5 – 92.2
Vancomycin91.587.2 – 94.3

Adverse events — posted to ClinicalTrials.gov

Time frame: All AEs were collected up to Day 13; only SAEs and drug related AEs were collected thereafter 30 days after end of treatment (up to Day 50). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Surotomycin
Serious: 44/305 (14%)
Deaths: 18/305
Vancomycin
Serious: 37/286 (13%)
Deaths: 9/286

Serious adverse events (83 terms)

ReactionSystemSurotomycinVancomycin
AnaemiaBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
PneumoniaInfections and infestations
DehydrationMetabolism and nutrition disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
IleusGastrointestinal disorders
Sudden cardiac deathGeneral disorders
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
Renal failure acuteRenal and urinary disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
Angina pectorisCardiac disorders
Atrial fibrillationCardiac disorders
Cardiac failureCardiac disorders
Cardiac failure congestiveCardiac disorders
Cardio-respiratory arrestCardiac disorders
Ventricular fibrillationCardiac disorders
Ventricular tachycardiaCardiac disorders
Abdominal wall haematomaGastrointestinal disorders
AscitesGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Duodenal ulcer haemorrhageGastrointestinal disorders
Inguinal hernia, obstructiveGastrointestinal disorders
Other adverse events (3 terms — click to expand)

ReactionSystemSurotomycinVancomycin
NauseaGastrointestinal disorders
HeadacheNervous system disorders
Abdominal painGastrointestinal disorders

Most-reported serious reactions: Anaemia, Cardiac arrest, Pneumonia, Dehydration, Chronic obstructive pulmonary disease, Ileus, Sudden cardiac death, Sepsis.

Data from ClinicalTrials.gov NCT01597505 adverse events section.

Sponsor's own description

606 participants with Clostridium Difficile Associated Diarrhea (CDAD) participated in this study and received either oral vancomycin or CB-183,315 (surotomycin) in a blinded fashion. Treatment lasted for 10 days and participants were followed up for at least 40 days and a maximum of 100 days. The purpose of this study was to evaluate how well surotomycin treats CDAD as compared to vancomycin.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Clostridium difficile infection.
    Smits WK, Lyras D, Lacy DB, Wilcox MH, et al · · 2016 · cited 678× · PMID 27158839 · DOI 10.1038/nrdp.2016.20
  2. The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions.
    Gan BH, Gaynord J, Rowe SM, Deingruber T, et al · · 2021 · cited 309× · PMID 34042120 · DOI 10.1039/d0cs00729c
  3. A New Era of Antibiotics: The Clinical Potential of Antimicrobial Peptides.
    Browne K, Chakraborty S, Chen R, Willcox MD, et al · · 2020 · cited 307× · PMID 32987946 · DOI 10.3390/ijms21197047
  4. Review: Lessons Learned From Clinical Trials Using Antimicrobial Peptides (AMPs).
    Dijksteel GS, Ulrich MMW, Middelkoop E, Boekema BKHL. · · 2021 · cited 260× · PMID 33692766 · DOI 10.3389/fmicb.2021.616979
  5. Antibiotics in the clinical pipeline in October 2019.
    Butler MS, Paterson DL. · · 2020 · cited 174× · PMID 32152527 · DOI 10.1038/s41429-020-0291-8
  6. Antimicrobial Peptides As Biologic and Immunotherapeutic Agents against Cancer: A Comprehensive Overview.
    Roudi R, Syn NL, Roudbary M. · · 2017 · cited 101× · PMID 29081781 · DOI 10.3389/fimmu.2017.01320
  7. Synthetic Biology and Computer-Based Frameworks for Antimicrobial Peptide Discovery.
    Torres MDT, Cao J, Franco OL, Lu TK, et al · · 2021 · cited 88× · PMID 33538585 · DOI 10.1021/acsnano.0c09509
  8. Recurrent Clostridium difficile infection: From colonization to cure.
    Shields K, Araujo-Castillo RV, Theethira TG, Alonso CD, et al · · 2015 · cited 77× · PMID 25930686 · DOI 10.1016/j.anaerobe.2015.04.012

Verify or expand the search:

Other recruiting trials for Clostridium Difficile Infection

Currently open trials in the same condition.

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Trials by the same sponsor.

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Data sources for this page

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing