This is a phase IIa, randomized, placebo-controlled, single-blinded superiority treatment study in males and non-pregnant females, 18 to 65 years of age who are in good health. This study is designed to compare placebo to once daily doses of 6mg auranofin for adults with amebiasis or giardiasis. A sample size of 68 subjects enrolled with amebiasis (34 per arm) and 68 with giardiasis (34 per arm); Power based on 60 subjects with amebiasis and 60 with giardiasis completing the study.Eligible subjects will be randomly assigned to a treatment group with auranofin (6 mg orally once daily for 5 days for giardiasis or 7 days for amebiasis) compared to a placebo group receiving similar but not identical placebo capsules. Projected duration of subject participation will be approximately 30 days of face to face visits, including the pre-enrollment screening period of up to 4 days. It is anticipated that it will take approximately 3.5 years to finish the study. Primary objectives are: 1) to compare the proportion of subjects with stools positive by rapid Enzyme Immunoassay (EIA) and positive antigen detection EIA for E. histolytica at enrollment with resolution of diarrhea (less than 3 loose stools/24 hrs) by Day 7 for E. histolytica infections. 2) to compare the proportion of subjects with stools positive by rapid EIA and positive antigen detection EIA for Giardia at enrollment with resolution of diarrhea (less than 3 loose stools/24 hrs) by Day 5 for Giardia infections.
This is a phase IIa, randomized, placebo-controlled, single-blinded superiority treatment study in males and non-pregnant females, 18 to 65 years of age who are in good health. This study is designed to compare placebo to once daily doses of 6mg auranofin for adults with amebiasis or giardiasis. A sample size of 68 subjects enrolled with amebiasis (34 per arm) and 68 with giardiasis (34 per arm); Power based on 60 subjects with amebiasis and 60 with giardiasis completing the study. Eligible subjects will be randomly assigned to a treatment group with auranofin (6 mg orally once daily for 5 days for giardiasis or 7 days for amebiasis) compared to a placebo group receiving similar but not identical placebo capsules. Projected duration of subject participation will be approximately 30 days of face to face visits, including the pre-enrollment screening period of up to 4 days. It is anticipated that it will take approximately 3.5 years to finish the study. Primary objectives are: 1) to compare the proportion of subjects with stools positive by rapid Enzyme Immunoassay (EIA) and positive antigen detection EIA for E. histolytica at enrollment with resolution of diarrhea (less than 3 loose stools/24 hrs) by Day 7 for E. histolytica infections. 2) to compare the proportion of subjects with stools positive by rapid EIA and positive antigen detection EIA for Giardia at enrollment with resolution of diarrhea (less than 3 loose stools/24 hrs) by Day 5 for Giardia infections. Secondary objectives for E. histolytica infections are: 1) to compare the proportion of subjects with stools positive by rapid EIA and positive antigen detection EIA for E. histolytica and trophozoites on smear at enrollment with parasitological response (no detection of trophozoites of E. histolytica on microscopic exam) by Day 7; 2) to compare the proportion of subjects with stools positive rapid EIA and positive antigen detection EIA for E. histolytica and trophozoites on smear at enrollment with parasitological response (no detection of trophozoites on microscopic exam or negative antigen detection) by Days 3 and 5; 3) to compare the rate of decrease of trophozoites/cyst load by Quantitative Polymerase Chain Reaction (qPCR) in stools by Days 3, 5, and 7; 4) to compare the proportion of subjects with negative stool antigen tests by days 3, 5, 7, and 14; 5) to compare the proportion of subjects with sustained cure (no detection of trophozoites by microscopic exam) at 14 and 28 days; 6) to compare the proportion of subjects with relapse (same strain) or re-infection (new strain) with positive stools at 14 and 28 days by genotyping the initial vs. subsequent strain; 7) to compare the time to resolution of diarrhea (less than 3 loose stools/24 hours). Secondary objectives for Giardia infections are: 1) to compare the proportion of subjects with parasitological response (no detection of trophozoites on microscopic exam ) on Day 3, and 5; 2) to compare the rate of decrease of trophozoites/cyst load by qPCR in stools by Days 3 and 5; 3) to compare the proportion of subjects with negative stool antigens by days 3 and 5; 4) to compare the proportion of subjects with sustained cure (no detection of trophozoites by microscopic exam) at 14 and 28 days; 5) to compare the proportion of subjects with relapse (same strain) or re-infection (new strain) with positive stools at 14 and 28 days by genotyping the initial vs. subsequent strain; 6) to compare the time to resolution of diarrhea (less than 3 loose stools/24 hours).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
93
International Center for Diarrheal Disease Research Bangladesh - Parasitology
Dhaka, Bangladesh
Rajshahi Medical College Hospital
Rajshahi, Bangladesh
Number of Participants With Positive Rapid Enzyme Immunoassay (EIA) and Positive Antigen Detection EIA for Giardia and Resolution of Diarrhea (Less Than 3 Loose Stools/24 Hours)
Diarrhea was assessed by self-report at each study visit. Resolution of diarrhea occurred when participants reported less than 3 loose stools in 24 hours.
Time frame: Day 5
Number of Participants With Positive Rapid Enzyme Immunoassay (EIA) and Positive Antigen Detection EIA for Giardia at Enrollment With Parasitological Response (no Detection of Cysts or Trophozoites on Microscopic Exam or Negative Antigen Test)
Participants provided stool samples on Day 5. Stool samples were assessed for parasitological response by detection of cysts or trophozoites via microscopic exam or a negative antigen test.
Time frame: Day 5
Proportion of Participants With Negative Giardia Stool Antigens
Participants provided stool samples on Days 3 and 5. Stool samples were tested for Giardia using antigen detection EIA. Proportions are calculated as the number of participants with negative Giardia stool antigen tests divided by the number of participants with results available.
Time frame: Day 3 through Day 5
Proportion of Symptomatic Participants With Positive Rapid EIA and Positive Antigen Detection EIA for Giardia and Trophozoites on Smear at Enrollment With Parasitological Response
Participants provided stool samples on Days 3 and 5. Stool samples were assessed for parasitological response by detection of trophozoites via microscopic exam. Proportions are calculated as the number of participants with parasitological response divided by the number of participants with results available.
Time frame: Day 3 through Day 5
Proportion of Symptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam)
Participants provided stool samples on Days 14 and 28. Stool samples were assessed for sustained Giardia cure by detection of trophozoites via microscopic exam. Proportion is calculated as the number of participants with sustained cure divided by the number of participants with results available.
Time frame: Day 14 through Day 28
Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools of Symptomatic Participants
Participants provided stool samples on Days 3 and 5. The Giardia trophozoite/cyst load (parasites/uL) for each group was then assessed by Quantitative Polymerase Chain Reaction (qPCR).
Time frame: Day 3 through Day 5
Time to Resolution of Diarrhea (Less Than 3 Loose Stools/24 Hours)
Diarrhea was assessed by self-report at each study visit. Resolution of diarrhea occurred when participants reported less than 3 loose stools in 24 hours.
Time frame: Day 1 through Day 28
Proportion of Participants With Positive Rapid Enzyme Immunoassay (EIA) and Positive Antigen Detection EIA for Giardia at Enrollment With Parasitological Response (no Detection of Cysts or Trophozoites on Microscopic Exam or Negative Antigen Test)
Participants provided stool samples on Day3. Stool samples were assessed for parasitological response by detection of cysts or trophozoites via microscopic exam or a negative antigen test. Proportions are calculated as the number of participants with parasitological response divided by the number of participants with results available.
Time frame: Day 3
Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools
Participants provided stool samples on Days 3 and 5. The Giardia trophozoite/cyst load (parasites/uL) for each group was then assessed by Quantitative Polymerase Chain Reaction (qPCR).
Time frame: Day 3 through Day 5
Proportion of Asymptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam)
Participants provided stool samples on Days 14 and 28. Stool samples were assessed for sustained Giardia cure by detection of cysts or trophozoites via microscopic exam or negative antigen detection. Proportions are calculated as the number of participants with sustained cure divided by the number of participants with results available.
Time frame: Day 14 through Day 28
Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain
Participants provided stool samples on Days 14 and 28. Any stool that was still positive for Giardia or trophozoites at Days 14 and 28 had DNA genotyping of the parasite performed on de-identified specimens of extracted DNA. The genotypes from initial and final isolates were compared to determine relapse and/or re-infection. Proportion is calculated as the number of participants with relapse or re-infection divided by the number of participants with results available.
Time frame: Day 14 through Day 28
Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain
Participants provided stool samples on Days 1, 14 and 28. Participants that were positive for Giardia via antigen detection at Day 1 and had a negative antigen detection test followed by a positive antigen detection test had DNA genotyping of the parasite performed on de-identified specimens of extracted DNA. The genotypes from initial (Day 1) and final isolates (Day 14/28) were compared to determine relapse and/or re-infection. Proportion is calculated as the number of participants with relapse or re-infection divided by the number of participants with results available.
Time frame: Day 1 through Day 28
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