Trial Outcomes & Findings for A Study of the Use of Oral Posaconazole (POS) in the Treatment of Asymptomatic Chronic Chagas Disease (P05267) (NCT NCT01377480)

Last Updated: 2018-08-27

Results Overview

Blood samples were collected for qualitative polymerase chain reaction (PCR) assay for Trypanosoma cruzi deoxyribonucleic acid (DNA). Successful response was defined as a negative qualitative PCR value at the Day 180 follow up visit.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

120 participants

Primary outcome timeframe

Day 180

Results posted on

2018-08-27

Participant Flow

A total of 393 participants were screened, 123 were eligible for enrollment, and 120 were randomized

Participant milestones

Participant milestones
Measure	Posaconazole POS 400 mg (10 mL) oral suspension twice daily for 60 days	Placebo POS placebo (10 mL) oral suspension twice daily for 60 days	Posaconazole + Benznidazole POS 400 mg (10 mL) oral suspension twice daily for 60 days and BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days	Benznidazole + Placebo BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days and POS placebo (10 mL) oral suspension twice daily for 60 days
Overall Study STARTED	32	30	28	30
Overall Study COMPLETED	32	29	18	19
Overall Study NOT COMPLETED	0	1	10	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo POS placebo (10 mL) oral suspension twice daily for 60 days	Posaconazole + Benznidazole POS 400 mg (10 mL) oral suspension twice daily for 60 days and BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days	Benznidazole + Placebo BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days and POS placebo (10 mL) oral suspension twice daily for 60 days
Overall Study Protocol Violation	0	0	4
Overall Study Evidence of drug-induced hepatotoxicity	1	1	0
Overall Study Withdrawal by Subject	0	1	0
Overall Study Serious adverse event	0	1	1
Overall Study Other	0	7	6

Baseline Characteristics

A Study of the Use of Oral Posaconazole (POS) in the Treatment of Asymptomatic Chronic Chagas Disease (P05267)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Posaconazole n=32 Participants POS 400 mg (10 mL) oral suspension twice daily for 60 days	Placebo n=30 Participants POS placebo (10 mL) oral suspension twice daily for 60 days	Posaconazole + Benznidazole n=28 Participants POS 400 mg (10 mL) oral suspension twice daily for 60 days and BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days	Benznidazole + Placebo n=30 Participants BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days and POS placebo (10 mL) oral suspension twice daily for 60 days	Total n=120 Participants Total of all reporting groups
Age, Continuous	40.3 years STANDARD_DEVIATION 8.6 • n=5 Participants	42.2 years STANDARD_DEVIATION 7.8 • n=7 Participants	40.2 years STANDARD_DEVIATION 8.4 • n=5 Participants	40.4 years STANDARD_DEVIATION 7.7 • n=4 Participants	40.8 years STANDARD_DEVIATION 8.1 • n=21 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants	17 Participants n=4 Participants	53 Participants n=21 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	23 Participants n=7 Participants	15 Participants n=5 Participants	13 Participants n=4 Participants	67 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 180

Population: The Full Analysis Population included all randomized subjects who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Posaconazole n=32 Participants POS 400 mg (10 mL) oral suspension twice daily for 60 days	Placebo n=30 Participants POS placebo (10 mL) oral suspension twice daily for 60 days	Posaconazole + Benznidazole n=28 Participants POS 400 mg (10 mL) oral suspension twice daily for 60 days and BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days	Benznidazole + Placebo n=30 Participants BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days and POS placebo (10 mL) oral suspension twice daily for 60 days
Percentage of Participants With a Successful Response as Measured by Qualitative Polymerase Chain Reaction	15.6 Percentage of participants Interval 6.9 to 31.8	10.0 Percentage of participants Interval 3.5 to 25.6	82.1 Percentage of participants Interval 64.4 to 92.1	86.7 Percentage of participants Interval 70.3 to 94.7

Adverse Events

Posaconazole

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Posaconazole + Benznidazole

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Benznidazole + Placebo

Serious events: 3 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Posaconazole n=32 participants at risk POS 400 mg (10 mL) oral suspension twice daily for 60 days	Placebo n=30 participants at risk POS placebo (10 mL) oral suspension twice daily for 60 days	Posaconazole + Benznidazole n=28 participants at risk POS 400 mg (10 mL) oral suspension twice daily for 60 days and BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days	Benznidazole + Placebo n=30 participants at risk BNZ 100 mg oral tablet twice daily (200-mg daily dose) for 60 days and POS placebo (10 mL) oral suspension twice daily for 60 days
Gastrointestinal disorders Diarrhoea	3.1% 1/32 • Number of events 1 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/30 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/28 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/30 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)
Hepatobiliary disorders Hepatitis	0.00% 0/32 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/30 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	3.6% 1/28 • Number of events 1 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/30 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)
Injury, poisoning and procedural complications Head injury	0.00% 0/32 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	3.3% 1/30 • Number of events 1 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/28 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/30 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)
Nervous system disorders Neuropathy peripheral	0.00% 0/32 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/30 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/28 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	3.3% 1/30 • Number of events 1 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/32 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/30 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/28 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	3.3% 1/30 • Number of events 1 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)
Skin and subcutaneous tissue disorders Photodermatosis	0.00% 0/32 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/30 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	3.6% 1/28 • Number of events 1 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/30 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)
Skin and subcutaneous tissue disorders Rash	0.00% 0/32 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/30 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	0.00% 0/28 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)	3.3% 1/30 • Number of events 1 • All adverse events: up to Day 90 (30 days post treatment); procedure-related serious adverse events: up to Day 360 (300 days post treatment)

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme, Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts with regard to proprietary information, accuracy, and fair-balance and compliance.
Publication restrictions are in place

Restriction type: OTHER