Trial Outcomes & Findings for PAR-101/OPT-80 Versus Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD) (NCT NCT00468728)

Last Updated: 2017-04-21

Results Overview

Percentage of subjects 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

535 participants

Primary outcome timeframe

Study day 10 (+/- 2 days)

Results posted on

2017-04-21

Participant Flow

Subjects were enrolled from April 2007 to November 2009 by centers in the United States, Canada, France, Spain, Belgium, Germany, United Kingdom, Italy, and Sweden.

Participant milestones

Participant milestones
Measure	Vancomycin 125 mg administered 4 times daily (q6hr)	PAR-101/OPT-80 200 mg administered twice daily (q12hr)
Enrollment STARTED	264	271
Enrollment COMPLETED	260	264
Enrollment NOT COMPLETED	4	7
Treatment STARTED	260	264
Treatment COMPLETED	256	253
Treatment NOT COMPLETED	4	11
Follow-up STARTED	256	253
Follow-up COMPLETED	222	222
Follow-up NOT COMPLETED	34	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Vancomycin 125 mg administered 4 times daily (q6hr)	PAR-101/OPT-80 200 mg administered twice daily (q12hr)
Treatment criteria for mITT population	4	11
Follow-up mITT failure	34	31

Baseline Characteristics

PAR-101/OPT-80 Versus Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vancomycin n=256 Participants 125 mg administered 4 times daily (q6hr)	PAR-101/OPT-80 n=253 Participants 200 mg administered twice daily (q12hr)	Total n=509 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 18.3 • n=5 Participants	64.1 years STANDARD_DEVIATION 18.0 • n=7 Participants	63.4 years STANDARD_DEVIATION 18.1 • n=5 Participants
Sex: Female, Male Female	161 Participants n=5 Participants	149 Participants n=7 Participants	310 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	104 Participants n=7 Participants	199 Participants n=5 Participants
Region of Enrollment France	8 participants n=5 Participants	11 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment United States	76 participants n=5 Participants	74 participants n=7 Participants	150 participants n=5 Participants
Region of Enrollment Canada	82 participants n=5 Participants	79 participants n=7 Participants	161 participants n=5 Participants
Region of Enrollment Spain	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Belgium	20 participants n=5 Participants	22 participants n=7 Participants	42 participants n=5 Participants
Region of Enrollment Germany	19 participants n=5 Participants	18 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment United Kingdom	27 participants n=5 Participants	26 participants n=7 Participants	53 participants n=5 Participants
Region of Enrollment Italy	13 participants n=5 Participants	14 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Sweden	7 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: Study day 10 (+/- 2 days)

Population: Analysis data is modified intent to treat (mITT) population. The mITT population consists of subjects that had CDAD confirmed by \>3 unformed bowel movements in the 24 hours prior to randomization and a positive toxin assay and received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Vancomycin n=256 Participants 125 mg administered 4 times daily (q6hr)	PAR-101/OPT-80 n=253 Participants 200 mg administered twice daily (q12hr)
Cure Rate at End of Therapy	86.7 Percentage of Participants Interval 82.0 to 90.4	87.7 Percentage of Participants Interval 83.1 to 91.2

SECONDARY outcome

Timeframe: Study days 11-40

Population: The analysis population is mITT, for subjects who met the primary endpoint of cure, was analyzed for the recurrence rates of diarrhea up to the Poststudy Visit.

Percentage of subjects with the re-establishment of diarrhea to an extent(based on frequency of passed unformed stools) that was greater than that noted on the last day of study medication, and the demonstration of either toxin A or B or both of C. difficile, and retreatment with CDI anti-infective therapy was needed.

Outcome measures

Outcome measures
Measure	Vancomycin n=222 Participants 125 mg administered 4 times daily (q6hr)	PAR-101/OPT-80 n=222 Participants 200 mg administered twice daily (q12hr)
Recurrence	27.0 Percentage of Participants	12.6 Percentage of Participants

SECONDARY outcome

Timeframe: End of Study

Population: The analysis population is mITT, subjects that achieved a cure response at end of treatment and not having a recurrence at any time up to the Post-study visit.

Achieving a cure response at end of treatment and not having a recurrence at any time up to the post-study visit.

Outcome measures

Outcome measures
Measure	Vancomycin n=256 Participants 125 mg administered 4 times daily (q6hr)	PAR-101/OPT-80 n=253 Participants 200 mg administered twice daily (q12hr)
Global Cure	63.3 Percentage of Participants	76.7 Percentage of Participants

Adverse Events

Vancomycin

Serious events: 58 serious events

Other events: 177 other events

Deaths: 0 deaths

PAR-101/OPT-80

Serious events: 70 serious events

Other events: 186 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Scientific Officer

Optimer Pharmaceuticals, Inc.

Phone: 1-855-343-4243

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Vancomycin n=260 participants at risk 125 mg administered 4 times daily (q6hr)	PAR-101/OPT-80 n=264 participants at risk 200 mg administered twice daily (q12hr)
Gastrointestinal disorders NAUSEA	11.5% 30/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	9.5% 25/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Gastrointestinal disorders VOMITING	7.7% 20/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	6.1% 16/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Gastrointestinal disorders DIARRHOEA	5.4% 14/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	3.0% 8/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Gastrointestinal disorders ABDOMINAL PAIN	4.2% 11/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	8.7% 23/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	3.5% 9/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	1.1% 3/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Gastrointestinal disorders CONSTIPATION	2.3% 6/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	4.2% 11/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Gastrointestinal disorders DYSPEPSIA	2.3% 6/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	0.76% 2/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Gastrointestinal disorders ABDOMINAL DISTENSION	1.9% 5/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	3.4% 9/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Gastrointestinal disorders FLATULENCE	1.2% 3/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.3% 6/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
General disorders FATIGUE	4.6% 12/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	3.4% 9/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
General disorders PYREXIA	3.8% 10/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.3% 6/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
General disorders OEDEMA PERIPHERAL	2.7% 7/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	1.5% 4/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Infections and infestations PNEUMONIA	3.1% 8/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.3% 6/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Infections and infestations URINARY TRACT INFECTION	1.9% 5/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.3% 6/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Infections and infestations CLOSTRIDIUM DIFFICILE COLITIS	1.2% 3/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.3% 6/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Infections and infestations SEPSIS	0.77% 2/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.3% 6/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Investigations ELECTROCARDIOGRAM QT PROLONGED	1.2% 3/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.7% 7/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Metabolism and nutrition disorders HYPOKALAEMIA	4.2% 11/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	6.8% 18/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Metabolism and nutrition disorders HYPERKALAEMIA	1.5% 4/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.3% 6/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Musculoskeletal and connective tissue disorders BACK PAIN	2.7% 7/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	1.1% 3/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	0.38% 1/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.3% 6/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Nervous system disorders HEADACHE	4.2% 11/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	5.7% 15/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Nervous system disorders DIZZINESS	2.7% 7/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	1.1% 3/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Psychiatric disorders INSOMNIA	1.9% 5/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.7% 7/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Respiratory, thoracic and mediastinal disorders COUGH	0.77% 2/260 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	2.7% 7/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.
Skin and subcutaneous tissue disorders PRURITUS	3.1% 8/260 • Number of events 8 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.	1.5% 4/264 • From Informed consent to 7-days following the last dose of study drug or until the last protocol-specified study visit, whichever occured later.