Amoebic Dysentery, Giardiasis
Conditions
Keywords
Amebiasis, Auranofin, GI Protozoa, Giardiasis, Placebo-Controlled, Reprofiled Drug, Single-Blind
Brief summary
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.
Detailed description
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).
Interventions
DRUGAuranofin
Auranofin is a gold-containing chemical salt available as 3mg capsules
OTHERPlacebo
Placebo
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent prior to initiation of any study procedures. 2. Able to understand and comply with planned study procedures and be available for all study visits. 3. Male or non-pregnant non-lactating females 18-65 years of age, inclusive. Females of reproductive potential currently using effective contraceptive methods are eligible. 4. Amebiasis or giardiasis identified by rapid Enzyme Immunoassay (EIA) and positive antigen detection EIA of stool \- if a subject is infected with both E. histolytica and Giardia, they will be enrolled in the E. histolytica study arm. Once the Entamoeba study arm is fully enrolled, any subsequent dual infected subjects will be enrolled in the Giardia arm. If a subject is infected with both Giardia and Cryptosporidium, they will not be enrolled. 5. Has diarrhea (defined as three or more loose stools) in the past 24 hrs, but is assessed to be clinically stable and in otherwise good health \- as determined by medical history and targeted physical examination, if indicated based on medical history, to evaluate acute or currently ongoing chronic medical diagnoses or conditions that would affect the assessment of eligibility and safety of subjects. Existing medical diagnoses or conditions (except those in the Subject
Exclusion criteria
) must be deemed as stable chronic medical conditions. A stable chronic medical condition is defined as no change in prescription medication, dose, or frequency of medication in the last 3 months (90 days) and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months (180 days). Any change due to change of health care provider, insurance company, or that is done for financial reasons, as long as in the same class of medication, will not be considered a violation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a violation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety. Topical, nasal, and inhaled medications, vitamins, and contraceptives are permitted. 6. Vital signs (oral temperature, pulse, and blood pressure) are all within normal protocol-defined ranges. 7. Laboratory tests (blood urea nitrogen, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), white blood cells, platelets, and hemoglobin) are all within protocol-defined ranges. Subjects will be eligible for enrollment with the following laboratory values: blood urea nitrogen less than or equal to 30 mg/dL, creatinine less than or equal to 133 umol/L, AST or ALT less than or equal to 70.0 U/L, white cell count between 3.5 and 13.0 inclusive (10\^9/L), platelets between 131 and 550 (10\^9/L), hemoglobin between 11.0 and 18.0 gm/dL inclusive. 8. Urinalysis with no greater than trace protein. If a high protein is confirmed to be due to menstruation, it should be repeated. 9. Women of reproductive potential must have a negative urine pregnancy test within 72 hours of starting study medications. \- Female subjects who are surgically sterile via tubal sterilization, bilateral oophorectomy or hysterectomy who have been postmenopausal for greater than 1 year are not considered to be of reproductive potential. 10. Female subjects participating in sexual activity that could lead to pregnancy must be using and continue to use highly effective contraception for a total of 4 months after enrollment. * Highly effective methods of contraception are defined as having low failure rates (i.e. less than 1 percent per year) when used consistently and correctly and may include, but are not limited to, abstinence from intercourse, monogamous relationship with a vasectomized partner, male condoms with spermicide, diaphragm with spermicide, intrauterine devices, and licensed hormonal methods. Females on effective forms of birth control will continue while on the study and for the follow-up period of 4 months total. The method and compliance of birth control used will be confirmed and documented at all study visits.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Day 5 | 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. |
| 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) | Day 5 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Symptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam) | Day 14 through Day 28 | 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. |
| Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools of Symptomatic Participants | Day 3 through Day 5 | 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 to Resolution of Diarrhea (Less Than 3 Loose Stools/24 Hours) | Day 1 through Day 28 | 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. |
| Proportion of Participants With Negative Giardia Stool Antigens | Day 3 through Day 5 | 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. |
| Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools | Day 3 through Day 5 | 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). |
| Proportion of Asymptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam) | Day 14 through Day 28 | 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. |
| Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 14 through Day 28 | 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. |
| 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) | Day 3 | 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. |
| Proportion of Symptomatic Participants With Positive Rapid EIA and Positive Antigen Detection EIA for Giardia and Trophozoites on Smear at Enrollment With Parasitological Response | Day 3 through Day 5 | 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. |
Countries
Bangladesh
Participant flow
Recruitment details
Participants were males and non-pregnant females between 18 to 65 years of age, inclusive, with amebiasis or giardiasis. Asymptomatic participants were recruited from the Mirpur community of Bangladesh by a randomized census. Symptomatic participants were identified by a health professional at either icddr,b or Rajshahi Medical College hospitals. Asymptomatic participants were enrolled from 06NOV2016 to 23APR2017. Symptomatic participants were enrolled from 16JAN2018 to 28JAN2021.
Participants by arm
| Arm | Count |
|---|---|
| Asymptomatic E. Histolytica- Placebo 6mg placebo daily x 7 days | 1 |
| Asymptomatic Giardia- Auranofin 6mg auranofin daily x 5 days | 17 |
| Asymptomatic Giardia- Placebo 6mg placebo daily x 5 days | 16 |
| Symptomatic Giardia- Auranofin 6mg auranofin daily x 5 days | 30 |
| Symptomatic Giardia- Placebo 6mg placebo daily x 5 days | 29 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | COVID-19 Pandemic | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Asymptomatic E. Histolytica- Placebo | Total | Asymptomatic Giardia- Auranofin | Asymptomatic Giardia- Placebo | Symptomatic Giardia- Auranofin | Symptomatic Giardia- Placebo |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 93 Participants | 17 Participants | 16 Participants | 30 Participants | 29 Participants |
| Age, Continuous | 36 years STANDARD_DEVIATION 0 | 34.6 years STANDARD_DEVIATION 9.2 | 38.6 years STANDARD_DEVIATION 9.3 | 33.5 years STANDARD_DEVIATION 8.2 | 34.2 years STANDARD_DEVIATION 9.5 | 33.4 years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 93 Participants | 17 Participants | 16 Participants | 30 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 93 Participants | 17 Participants | 16 Participants | 30 Participants | 29 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Bangladesh | 1 participants | 93 participants | 17 participants | 16 participants | 30 participants | 29 participants |
| Sex: Female, Male Female | 1 Participants | 22 Participants | 10 Participants | 10 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 71 Participants | 7 Participants | 6 Participants | 30 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 17 | 0 / 16 | 0 / 30 | 0 / 29 |
| other Total, other adverse events | 0 / 1 | 9 / 17 | 7 / 16 | 0 / 30 | 2 / 29 |
| serious Total, serious adverse events | 0 / 1 | 0 / 17 | 0 / 16 | 0 / 30 | 0 / 29 |
Outcome results
Primary
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
Population: Modified Intention to Treat Population: All symptomatic participants who were randomized with available results, dispensed at least one dose of study medication, and had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Symptomatic Giardia- Auranofin | 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) | 28 Participants |
| Symptomatic Giardia- Placebo | 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) | 28 Participants |
Comparison: The null hypothesis is that the probability of resolution of diarrhea by Day 5 for participants receiving auranofin is equal to that for those receiving placebo.p-value: >0.99995% CI: [-0.12, 0.12]Fisher Exact
Primary
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
Population: Modified Intention to Treat Population: All asymptomatic participants who were randomized, dispensed at least one dose of study medication, and had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Symptomatic Giardia- Auranofin | 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) | 6 Participants |
| Symptomatic Giardia- Placebo | 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) | 6 Participants |
Comparison: The null hypothesis is that the probability of parasitological response by Day 5 for participants receiving auranofin is equal to that for those receiving placebo.p-value: >0.99995% CI: [-0.34, 0.34]Fisher Exact
Secondary
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
Population: Modified Intention to Treat Population: All asymptomatic participants who were randomized, dispensed at least one dose of study medication, and had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Symptomatic Giardia- Auranofin | Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools | Day 3 | 7.5 log parasite load/uL |
| Symptomatic Giardia- Auranofin | Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools | Day 5 | 7.1 log parasite load/uL |
| Symptomatic Giardia- Placebo | Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools | Day 3 | 9.0 log parasite load/uL |
| Symptomatic Giardia- Placebo | Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools | Day 5 | 8.5 log parasite load/uL |
Secondary
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
Population: Modified Intention to Treat Population: All symptomatic participants who were randomized, dispensed at least one dose of study medication, had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment, with available results.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Symptomatic Giardia- Auranofin | Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools of Symptomatic Participants | Day 3 | 8.6 log parasite load/uL |
| Symptomatic Giardia- Auranofin | Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools of Symptomatic Participants | Day 5 | 8.2 log parasite load/uL |
| Symptomatic Giardia- Placebo | Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools of Symptomatic Participants | Day 5 | 8.1 log parasite load/uL |
| Symptomatic Giardia- Placebo | Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools of Symptomatic Participants | Day 3 | 9.2 log parasite load/uL |
Secondary
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
Population: Modified Intention to Treat Population: All asymptomatic participants who were randomized, dispensed at least one dose of study medication, and had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Symptomatic Giardia- Auranofin | Proportion of Asymptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam) | Day 14 | 0.29 proportion of participants |
| Symptomatic Giardia- Auranofin | Proportion of Asymptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam) | Day 28 | 0.29 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Asymptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam) | Day 14 | 0.21 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Asymptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam) | Day 28 | 0.14 proportion of participants |
Secondary
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
Population: Modified Intention to Treat Population: All symptomatic participants who were randomized, dispensed at least one dose of study medication, had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Symptomatic Giardia- Auranofin | Proportion of Participants With Negative Giardia Stool Antigens | Day 3 | 0.45 proportion of participants |
| Symptomatic Giardia- Auranofin | Proportion of Participants With Negative Giardia Stool Antigens | Day 5 | 0.55 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Participants With Negative Giardia Stool Antigens | Day 3 | 0.38 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Participants With Negative Giardia Stool Antigens | Day 5 | 0.34 proportion of participants |
Secondary
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
Population: Modified Intention to Treat Population: All participants who were randomized, dispensed at least one dose of study medication, and had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symptomatic Giardia- Auranofin | 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) | 0.43 proportion with parasitological response |
| Symptomatic Giardia- Placebo | 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) | 0.29 proportion with parasitological response |
Secondary
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
Population: Modified Intention to Treat Population: All symptomatic participants who were randomized, dispensed at least one dose of study medication, and had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Symptomatic Giardia- Auranofin | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 14 - Relapse | 0.08 proportion of participants |
| Symptomatic Giardia- Auranofin | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 14 - Re-infection | 0.00 proportion of participants |
| Symptomatic Giardia- Auranofin | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 28 - Relapse | 0.11 proportion of participants |
| Symptomatic Giardia- Auranofin | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 28 - Re-infection | 0.00 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 28 - Re-infection | 0.14 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 14 - Relapse | 0.07 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 28 - Relapse | 0.07 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 14 - Re-infection | 0.07 proportion of participants |
Secondary
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
Population: Modified Intention to Treat Population: All asymptomatic participants who were randomized, dispensed at least one dose of study medication, and had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Symptomatic Giardia- Auranofin | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 14 - Relapse | 0.58 proportion of participants |
| Symptomatic Giardia- Auranofin | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 14 - Re-infection | 0.33 proportion of participants |
| Symptomatic Giardia- Auranofin | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 28 - Relapse | 0.63 proportion of participants |
| Symptomatic Giardia- Auranofin | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 28 - Re-infection | 0.25 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 28 - Re-infection | 0.09 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 14 - Relapse | 0.75 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 28 - Relapse | 0.73 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Participants With Relapse (Same Strain) or Re-infection (New Strain) With Giardia-positive Stools by Genotyping the Initial vs. Subsequent Strain | Day 14 - Re-infection | 0.25 proportion of participants |
Secondary
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
Population: Modified Intention to Treat Population: All symptomatic participants who were randomized, dispensed at least one dose of study medication, and had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Symptomatic Giardia- Auranofin | Proportion of Symptomatic Participants With Positive Rapid EIA and Positive Antigen Detection EIA for Giardia and Trophozoites on Smear at Enrollment With Parasitological Response | Day 3 | 0.97 proportion of participants |
| Symptomatic Giardia- Auranofin | Proportion of Symptomatic Participants With Positive Rapid EIA and Positive Antigen Detection EIA for Giardia and Trophozoites on Smear at Enrollment With Parasitological Response | Day 5 | 0.97 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Symptomatic Participants With Positive Rapid EIA and Positive Antigen Detection EIA for Giardia and Trophozoites on Smear at Enrollment With Parasitological Response | Day 3 | 0.93 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Symptomatic Participants With Positive Rapid EIA and Positive Antigen Detection EIA for Giardia and Trophozoites on Smear at Enrollment With Parasitological Response | Day 5 | 1.00 proportion of participants |
Secondary
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
Population: Modified Intention to Treat Population: All symptomatic participants who were randomized, dispensed at least one dose of study medication, and had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Symptomatic Giardia- Auranofin | Proportion of Symptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam) | Day 14 | 0.96 proportion of participants |
| Symptomatic Giardia- Auranofin | Proportion of Symptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam) | Day 28 | 0.96 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Symptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam) | Day 14 | 0.90 proportion of participants |
| Symptomatic Giardia- Placebo | Proportion of Symptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam) | Day 28 | 0.89 proportion of participants |
Secondary
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
Population: Modified Intention to Treat Population: All symptomatic participants who were randomized, dispensed at least one dose of study medication, had a positive rapid EIA and positive antigen detection EIA for Giardia at enrollment, with available results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Symptomatic Giardia- Auranofin | Time to Resolution of Diarrhea (Less Than 3 Loose Stools/24 Hours) | 3 days |
| Symptomatic Giardia- Placebo | Time to Resolution of Diarrhea (Less Than 3 Loose Stools/24 Hours) | 3 days |
Comparison: The null hypothesis is that there is no difference in time to resolution of diarrhea between treatment arms, with a two-sided alternative.p-value: 0.142Log Rank