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Fidaxomicin

Phase 3

Clostridium Difficile-associated Diarrhea (CDAD) | Small molecule | Gastrointestinal |Merck & Company, Inc.|Last Updated: Nov 26, 2024

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials2
Total Enrollment759

FDA Designations

No designations recorded

Clinical trial landscape

Fidaxomicin · 6 trials · 9 indications

Phase 3 3Phase 2 1Phase 1 2
NCT02218372A Study to Investigate the Safety and Efficacy of Fidaxomicin (Oral Suspension or Tablets) and Vancomycin (Oral Liquid or Capsules) in Pediatric Subjects With Clostridium Difficile-associated Diarrhea (CDAD)Clostridium Difficile-associated Diarrhea (CDAD)
COMPLETED148 Analytics
NCT01691248Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001)Clostridium Difficile-Associated Diarrhea (CDAD)
COMPLETED611 Analytics
NCT00314951Fidaxomicin Versus Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD) (MK-5119-018)Clostridium Infections
COMPLETED629 Analytics
PHASE3COMPLETED
A Study to Investigate the Safety and Efficacy of Fidaxomicin (Oral Suspension or Tablets) and Vancomycin (Oral Liquid or Capsules) in Pediatric Subjects With Clostridium Difficile-associated Diarrhea (CDAD)
Clostridium Difficile-associated Diarrhea (CDAD)Unlock trial analytics
PHASE3COMPLETED
Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001)
Clostridium Difficile-Associated Diarrhea (CDAD)Unlock trial analytics
PHASE3COMPLETED
Fidaxomicin Versus Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD) (MK-5119-018)
Clostridium InfectionsUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants With Confirmed Clinical Response (CCR) at End of Treatment (EOT) +2 Days
Up to day 12

Initial clinical response (ICR) for ages from birth to \< 2 years was defined as absence of watery diarrhea for 2 consecutive treatment days, remaining well until study drug discontinuation. ICR for ages ≥ 2 years to \< 18 years was defined as improvement in number and character of bowel movements as determined by \< 3 unformed bowel movements (UBMs) per day for 2 consecutive treatment days, remaining well until study drug discontinuation. CCR was defined for both age groups as not requiring further CDAD therapy within 2 days after study drug completion, and was reported with a positive (Yes) or negative (No) outcome. Resolution of diarrhea was assessed during interviews of participant/parent/legal guardian, supplemented by review of personal records (if hospitalized) and checked for presence of watery diarrhea (ages from birth to \< 2 years) or number of UBMs (for ages ≥ 2 years to \< 18 years).

Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 30 Days Post-treatment Follow-up.
Up to 30 days post-treatment

CDAD is defined as follows: Diarrhea: (change in bowel habits with \>3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.

Cure Rate at End of Therapy
Study day 10 (+/- 2 days)

Percentage of participants with 3 or fewer unformed stools for 2 consecutive days and maintained through the end of therapy, and the subject no longer needed specific anti-Clostridium antibacterial treatment after completion of the course of study medication.

Number of Participants With Adverse Events.
Enrollment through end of study (Day 38-41)

Number of participants with adverse events, as categorized by MedDRA.

Investigate Concentrations of Fidaxomicin in Plasma Samples.
3-5 hours after administration

3-5 hour plasma levels of fidaxomicin (mean)

Investigate Concentrations of Fidaxomicin in Fecal Samples.
End of Therapy; Day 10-11

End of therapy fecal levels of fidaxomicin (mean)

Investigate Concentrations of the Main Metabolite OP-1118 in Plasma Samples.
3-5 hours after administration

3-5 hour plasma levels of OP-1118 (mean)

Investigate Concentrations of the Main Metabolite OP-1118 in Fecal Samples.
End of Therapy; Day 10-11

End of therapy fecal levels of OP-1118 (mean)

Pharmacokinetics (PK) of fidaxomicin in plasma (single dose): Lag time (tlag)
Days 1-5 (14 times)
PK of fidaxomicin plasma (single dose): Time to attain maximum concentration (tmax)
Days 1-5 (14 times)
PK of fidaxomicin in plasma (single dose): Maximum Concentration (Cmax)
Days 1-5 (14 times)
PK of fidaxomicin in plasma (single dose): Area Under the Plasma Concentration - Time Curve (AUC) from Time Zero to Time of Last Measurable Concentration (AUClast)
Days 1-5 (14 times)
PK of fidaxomicin in plasma (single dose): AUC - Time Curve from Time Zero to Infinity (aucinf)
Days 1-5 (14 times)
PK of fidaxomicin in plasma (single dose): AUC - Time Curve from Time Zero to 12 hours (AUC 0-12h)
Days 1-5 (14 times)
PK of fidaxomicin in plasma (single dose): Total Body Clearance after Single Dose (CL/F)
Days 1-5 (14 times)
PK of fidaxomicin in plasma (single dose): Apparent Volume of Distribution During Terminal Phase (Vz/F)
Days 1-5 (14 times)
PK of fidaxomicin in plasma (last dose): Apparent Volume of Distribution During Terminal Phase (Vz/F)
Days 15-17 (11 times)
PK of fidaxomicin in plasma (single dose): Apparent Terminal elimination Half-life (t 1/2)
Days 1-5 (14 times)

Single Dose

PK of fidaxomicin in plasma (last dose): Apparent Terminal elimination Half-life (t 1/2)
Days 15-17 (11 times)

Single Dose

PK of fidaxomicin in plasma (single dose): Trough levels
Days 6, 7, 10, and 12 (pre-morning dose)
PK of fidaxomicin in plasma (last dose): tmax at Steady State (tmax, ss)
Days 15-17 (11 times)

Last Dose

PK of fidaxomicin in plasma (last dose): Cmax at Steady State (Cmax, ss)
Days 15-17 (11 times)

Last Dose

PK of fidaxomicin in plasma (last dose): AUC Over the dosing Interval (AUCtau)
Days 15-17 (11 times)
PK of fidaxomicin in plasma (last dose): CL/F at Steady State (CL/F ss)
Days 15-17 (11 times)
PK of fidaxomicin in plasma (last dose): Peak: Trough Ratio (PTR)
Days 15-17 (11 times)
PK of fidaxomicin in plasma (last dose): Accumulation Ratio (Racc)
Days 15-17 (11 times)
PK of fidaxomicin in plasma (last dose): Pre-dose Plasma Concentration Determined Directly from the Concentration-Time Profile (Ctrough)
Days 15-17 (11 times)
PK of fidaxomicin in urine (last dose): Cumulative Amount of Drug Excreted in the urine from Time Zero to Time of Last Measurable Concentration (Aelast)
Days 1-5 (6 times)
PK of fidaxomicin in urine (single dose): Percent Fraction of Administered Drug Excreted Unchanged in the urine from Time Zero to Time of Last Measurable Concentration (% Aelast )
Days 1-5 (6 times)
PK of fidaxomicin in urine (single dose): Cumulative Amount of Drug Excreted in the Urine from time Zero to Infinity after Single Dose (Aeinf)
Days 1-5 (6 times)
PK of fidaxomicin in urine (single dose): Percent Fraction of administered drug excreted unchanged in the urine from time Zero to Infinity after Single Dose (% Aeinf)
Days 1-5 (6 times)
PK of fidaxomicin in urine (single dose): Renal Clearance (CL/R
Days 1-5 (6 times)
PK of fidaxomicin in urine (last dose): Cumulative Amount of Drug Excreted in the urine over the dosing Interval at Steady State (Aetau)
Day 15 (1 time)
PK of fidaxomicin in urine (last dose): Percent Fraction of Administered Drug Excreted Unchanged in the Urine over the Dosing Interval at Steady State (% Aetau)
Day 15 (1 time)
PK of fidaxomicin in urine (last dose): Renal Clearance at Steady State (CLR,ss)
Day 15 ( 1 time)
PK of fidaxomicin in feces (single dose): Amount of Drug Excreted in the Feces (Ae)
Days 1-5 (5 times)
PK of fidaxomicin in feces (last dose): Amount of Drug Excreted in the Feces (Ae)
Days 15-17 (first bowel movement (BM) following the last dose to be collected)
PK of fidaxomicin in feces (single dose): Percent Fraction of Administered Drug Excreted Unchanged in the Feces (%Ae)
Days 1-5 (5 times)
PK of fidaxomicin in feces (last dose): Percent Fraction of Administered Drug Excreted Unchanged in the Feces (%Ae)
Days 15-17 (first BM following the last dose to be collected)
Effect of multiple doses of fidaxomicin on the single dose pharmacokinetics of rosuvastatin as measured by maximum observed concentration
Day 1-6 (sequence1/period1) & Day 13-18 (sequence1/period2) Day 6-11 (sequence2/period1) & Day 14-19 (sequence2/period2)

Cmax (maximum observed concentration)

Effect of multiple doses of fidaxomicin on the single dose pharmacokinetics of rosuvastatin as measured by area under the concentration time curve from time zero extrapolated to infinity
Day 1-6 (sequence1/period1) & Day 13-18 (sequence1/period2) Day 6-11 (sequence2/period1) & Day 14-19 (sequence2/period2)

AUCinf (area under the concentration time curve from time zero extrapolated to infinity)

Secondary Endpoints

Percentage of Participants With Sustained Clinical Response (SCR) at EOT +9 Days
Up to day 19
Percentage of Participants With Global Cure (GC) at EOT +9 Days
Up to day 19
Percentage of Participants With Recurrence of CDAD at EOT +9 Days
Up to day 19
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Study Design & Arms

AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
FidaxomicinEXPERIMENTALParticipants from birth to \< 6 years of age received weight based doses of fidaxomicin oral suspension (32 mg/kg/day with a maximum dose of 400 mg/day divided in 2 doses) 2 times daily for 10 days. Participants aged ≥ 6 years to \< 18 years of age received a 200 mg fidaxomicin tablet 2 times daily for 10 days.
VancomycinACTIVE_COMPARATORParticipants from birth to \< 6 years of age received weight based doses of vancomycin oral liquid (40 mg/kg/day with a maximum dose of 500 mg/day divided in 4 doses) 4 times daily for 10 days. Participants aged ≥ 6 years to \< 18 years of age received a 125 mg vancomycin capsule 4 times daily for 10 days.
PlaceboPLACEBO_COMPARATORPlacebo tablet once daily for no longer than 40 days
Cohort 1: Fidaxomicin low dose in Japanese malesEXPERIMENTAL -
Cohort 2: Fidaxomicin high dose in Japanese malesEXPERIMENTAL -
Cohort 3: Fidaxomicin high dose in Caucasian malesEXPERIMENTAL -
Matching Placebo in Caucasian malesPLACEBO_COMPARATOR -
Matching Placebo in Japanese malesPLACEBO_COMPARATOR -
1:Single rosuvastatin,multiple fidaxomicin,single rosuvastatinEXPERIMENTAL -
2:Multiple fidaxomicin,single rosuvastatin,single rosuvastatinEXPERIMENTAL -

Interventions

NameTypeDescription
Fidaxomicin oral suspensionDRUGParticipants from birth to \< 6 years of age received weight based doses of fidaxomicin oral suspension (32 mg/kg/day with a maximum dose of 400 mg/day divided in 2 doses) 2 times daily for 10 days.
Fidaxomicin tabletsDRUGParticipants aged ≥ 6 years to \< 18 years of age received a 200 mg fidaxomicin tablet 2 times daily for 10 days.
Vancomycin oral liquidDRUGParticipants from birth to \< 6 years of age received weight based doses of vancomycin oral liquid (40 mg/kg/day with a maximum dose of 500 mg/day divided in 4 doses) 4 times daily for 10 days.
Vancomycin capsulesDRUGParticipants aged ≥ 6 years to \< 18 years of age received a 125 mg vancomycin capsule 4 times daily for 10 days.
fidaxomicinDRUGFidaxomicin 200 mg tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Study drug treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later). Study drug treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days.
PlaceboDRUGPlacebo tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later). Treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days.
VancomycinDRUG125 mg capsules q6hr (4 times a day)
Matching Placebo to FidaxomicinDRUGMatching Placebo to Fidaxomicin administered two times daily (intermittently with fidaxomicin dosing)
rosuvastatinDRUGOral
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Eligibility Criteria

Age RangeN/A to 17 Years
SexALL
Healthy VolunteersNo
Study Sites44

Inclusion Criteria: * Subject is diagnosed with CDAD according to local diagnostic criteria. As a minimum there must be positive detection, within 72 hours prior to randomization, of either toxin A and/or toxin B in stool or positive detection of toxigenic C. difficile in stool and: * Subject fr...

Countries:United StatesBelgiumCanadaFranceGermanyHungaryItalyPolandRomaniaSpain
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Frequently asked questions about Fidaxomicin

What is fidaxomicin used for?

Fidaxomicin is used for Clostridium difficile-associated diarrhea (CDAD), also called Clostridium difficile infection. It is a small molecule gastrointestinal drug being developed by Merck & Company, Inc. (MRK). Fidaxomicin is an investigational agent and has been studied in clinical trials for the treatment of CDAD.

What does fidaxomicin target?

Fidaxomicin is a macrocyclic antibiotic that targets Clostridium difficile bacteria. It works by inhibiting bacterial RNA polymerase, which disrupts bacterial protein synthesis and leads to bacterial cell death. This mechanism is specific to the treatment of Clostridium difficile infections.

Who makes fidaxomicin?

Fidaxomicin is developed by Merck & Company, Inc., which trades under the ticker MRK. Merck is conducting clinical trials to evaluate fidaxomicin for the treatment of Clostridium difficile-associated diarrhea (CDAD).

What phase is fidaxomicin in?

Fidaxomicin has completed Phase 3 clinical trials for Clostridium difficile-associated diarrhea (CDAD). The Phase 3 trial, NCT00314951, compared fidaxomicin to vancomycin in 629 patients. Fidaxomicin is not yet approved and remains an investigational drug in clinical development.

What clinical trials is fidaxomicin in?

Fidaxomicin has been studied in several completed trials. NCT00314951 was a Phase 3 trial comparing fidaxomicin to vancomycin for CDAD in 629 patients. NCT01591863 was a Phase 2 pediatric trial in 38 subjects with CDAD. NCT01813448 and NCT02083627 were Phase 1 pharmacokinetic and drug-drug interaction studies in healthy volunteers.

Is fidaxomicin the same as OPT-80?

Fidaxomicin is also known by the development code OPT-80. It is a macrocyclic antibiotic being developed by Merck & Company, Inc. for the treatment of Clostridium difficile-associated diarrhea (CDAD). The drug has been evaluated in Phase 3 clinical trials.