Neurocysticercosis
Conditions
Keywords
neurocysticercosis, pork tapeworm, Taenia solium
Brief summary
The objectives of the Phase I study are to evaluate the safety and tolerance of increasing single oral doses of oxfendazole in healthy volunteers.The secondary objectives assess the pharmacokinetic profile of oxfendazole and assess the metabolism of oxfendazole. The description of agent used is single oral dose of an aqueous suspension of oxfendazole, a benzimidazole carbamate antiparasitic drug. Each new cohort will be dosed only after the two week safety data for the preceding group have been reviewed. If a clinically significant AE is observed, and if this event is drug-related the safety monitoring committee will be convened to determine whether the study should continue.
Detailed description
This Phase I study is a randomized, double-blind, placebo-controlled evaluation of the safety and pharmacokinetics of escalating single oral doses of oxfendazole (0.5 to 60 mg/kg) in healthy volunteers. Up to 70 healthy males and females (non-chldbearing potential), ages 18-45 volunteers recruited from one site will participate in this study. The study duration is approximately 18 months with subject participation of 2 weeks. The primary objective assess the safety and tolerability of oxfendazole in healthy adults. The secondary objectives assess the pharmacokinetic profile of oxfendazole and assess the metabolism of oxfendazole. Two sentinel subjects will receive the study product (1 drug/1 placebo) in each group and be monitored 48 hours for adverse events prior to completing enrollment of the remaining 8 subjects in the group.
Interventions
DRUGOxfendazole
A benzimidazole carbamate antiparasitic drug. Oral Dose levels of 0.5,1, 3, 7.5, 15, 30, and 60 mg/kg will be evaluated sequentially, the dose increasing with each new cohort Group 1 to Group 7.
OTHERPlacebo
Normal Saline administered with an oral dosing syringe. Group 1- Group 6
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Males and females of non-childbearing potential between the ages of 18 and 45 years, inclusive.\* \*Surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy or who have been postmenopausal for \>/=1 year confirmed by LH and FSH levels. 2. In good health, as judged by the investigator and determined by vital signs\* Temperature \< 38 degrees Celsius, heart rate \</=100 bpm and \> 50 bpm, systolic blood pressure \</= 140 mmHg and \> 89 mmHg, diastolic blood pressure \</=90 mmHg and \>/= 60 mm Hg, medical history and a targeted physical examination. BMI \>/=18 and \</= 35. Athletically trained subjects with a pulse \>/= 45 may be enrolled at the discretion of the principal investigator or designated licensed clinical investigator. 3. Acceptable screening laboratories\* \*Hemoglobin, white blood cell (WBC) count, neutrophil, eosinophil and platelet counts within normal ranges. AST \< 44 and ALT \< 44 and total bilirubin, creatinine must be equal to or below the upper limit of normal (for eosinophil count, AST, ALT, creatinine, and total bilirubin values below the normal range are acceptable). Random blood glucose must be \<140. Urine dipstick testing must be negative for glucose and negative or trace for protein. The following serology tests must be negative: HIV 1/2 antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody. HIV and hepatitis C viral load PCR testing may be performed for individuals suspected of having indeterminate antibody testing. 4. Male participants must be willing to ensure use of condoms and spermicides for 4 months after study drug administration. 5. Provide written informed consent before initiation of any study procedures. 6. Willing to be available for all study-required procedures, and visits for the duration of the study. 7. Able to provide a home phone number, and the name, address, and/or email of a person willing to assist with making contact during the follow-up phase of the study.
Exclusion criteria
1\. History of residing for 6 or more months in regions with endemic cysticercosis as determined by the principal investigator or a designated study physician. 2. Breastfeeding females. 3. Body temperature \>/=100.4 degrees Fahrenheit (\>/=38.0 degrees Celsius) or acute illness within 3 days before administration of study drug (subject may be rescheduled). 4. Chronic or acute medical disorder\* \*Disorders of the cardiac, pulmonary, liver, kidney, neurologic, gastrointestinal or other system, such that in the opinion of the investigator participation in the study creates additional risk to the subject, or to the validity of the study. 5. Use of chronic systemic medications\* \*Intermittent use of over the counter medications such as acetaminophen, ibuprofen, cold and sinus medications are permitted for enrollment (please see section 5.6 for instructions on medication use during the study).Topical medications, nasal steroids are permitted throughout the study. Use of the prescription medications used less than once per week on average are permitted for enrollment (see section 5.6 for instructions on medication use during the study). If the subject has taken a short term prescription medication within the past 30 days (e.g. an antibiotic), they should be postponed from enrollment until 30 days have elapsed since the last dose 6. Has history of sensitivity to related benzimidazole compounds (e.g., albendazole, mebendazole). 7. A diagnosis of schizophrenia, bipolar disease, or history of hospitalization for a psychiatric condition or previous suicide attempt. 8. A history of treatment for any other psychiatric disorder in the past 3 years.\* \*Past treatment for ADHD does not exclude participants from enrollment as long as the medications have been discontinued for a minimum of 3 months and symptoms are well controlled. 9. Received an experimental agent\* within 1 month before administration of study drug or expect to receive an experimental agent during the 15-day study period. \*Vaccine, drug, biologic, device, blood product, or medication. 10. Any condition that would, in the opinion of the investigator, place them at an unacceptable risk of injury, render them unable to meet the requirements of the protocol, or that may interfere with successful completion of the study. 11. A history of alcohol consumption\* or any illicit drug use†, or history of substance abuse#. Individuals must agree to abstain from drug or alcohol use for 48 hours prior to enrollment through day 15. \*Greater than 7 alcoholic drinks per week. †Other than occasional marijuana use (less than once per week for the past 60 days is acceptable). #Alcohol or illicit drugs within the past 3 years. 12. History of chronic tobacco use in the past 60 days.\* \*A history of occasional tobacco use (less than 1 pack per week on average) is acceptable. Individuals will be counseled to abstain from use of tobacco and marijuana from screening through day 15.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose. | Within 14 Days of first dose | All adverse events, defined as any untoward medical occurrence regardless of its causal relationship to the study treatment, were collected for 14 days after dosing. The PI then determined relatedness to the study drug. Related was defined as there is a reasonable possibility that the study product caused the adverse event. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma | 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose | Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations computed from concentrations that were measured using a validated HPLC-MS/MS method. |
| Plasma Concentrations of Oxfendazole Fenbendazole | Day 1-Day15 | Concentrations of oxfendazole fenbendazole in plasma were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics. |
| Plasma Concentrations of Oxfendazole Sulfone | Day 1-Day15 | Concentrations of oxfendazole sulfone in plasma were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics. |
| Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole | 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose | AUC(0-infinity) was defined as the total area under the concentration-time curve from dosing (time 0) taken to the limit as the end time becomes arbitrarily large. AUC(0-infinity) and was calculated by adding AUC(0-last) to an extrapolated value equal to the last measured concentration greater than the lower limit of quantification of the bioanalytical assay divided by the terminal phase elimination rate constant (Ke) computed from concentrations that were measured using a validated HPLCMS/MS method |
| Time of Maximum Observed Concentration (Tmax) of Oxfendazole | 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose | Tmax was defined as the time at which the maximum concentration (Cmax) occurs in plasma computed from concentrations that were measured using a validated HPLCMS/MS method. |
| Urine Concentrations of Oxfendazole Fenbendazole | Day 1-Day 15 | Concentrations of oxfendazole fenbendazole in urine were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics. |
| Urine Concentrations of Oxfendazole Sulfone | Day 1-Day 15 | Concentrations of oxfendazole sulfone in urine were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics. |
| Terminal Elimination Half-life (t1/2) of Oxfendazole | 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose | The apparent terminal elimination half-life (t1/2) was defined as the time required for the drug concentration to decrease by a factor of one-half in the terminal phase computed from concentrations that were measured using a validated HPLCMS/MS method. |
Countries
United States
Participant flow
Recruitment details
Participants were healthy adult males and non-pregnant females recruited from existing volunteer populations and from the communities at large around the clinical site. Participants were enrolled between 17NOV2014 and 09NOV2015.
Participants by arm
| Arm | Count |
|---|---|
| 0.5 mg/kg Oxfendazole Participants received a single oral dose 0.5 mg/kg of oxfendazole. | 8 |
| 1 mg/kg Oxfendazole Participants received a single oral dose 1 mg/kg of oxfendazole | 8 |
| 3 mg/kg Oxfendazole Participants received a single oral dose 3 mg/kg of oxfendazole | 8 |
| 7.5 mg/kg Oxfendazole Participants received a single oral dose 7.5 mg/kg of oxfendazole | 8 |
| 15 mg/kg Oxfendazole Participants received a single oral dose 15 mg/kg of oxfendazole | 8 |
| 30 mg/kg Oxfendazole Participants received a single oral dose 30 mg/kg of oxfendazole | 8 |
| 60 mg/kg Oxfendazole Participants received a single oral dose 60 mg/kg of oxfendazole | 8 |
| Placebo Participants received a single placebo formulation consisting of 4.5% polyethylene glycol, 0.18% methyl paraben, and 95.32% sterile water for injection | 14 |
| Total | 70 |
Baseline characteristics
| Characteristic | 1 mg/kg Oxfendazole | 3 mg/kg Oxfendazole | 7.5 mg/kg Oxfendazole | 15 mg/kg Oxfendazole | 30 mg/kg Oxfendazole | 60 mg/kg Oxfendazole | 0.5 mg/kg Oxfendazole | Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 14 Participants | 70 Participants |
| Age, Continuous | 26.6 years STANDARD_DEVIATION 6.8 | 23.8 years STANDARD_DEVIATION 6.1 | 26.3 years STANDARD_DEVIATION 7.1 | 26.8 years STANDARD_DEVIATION 9.3 | 22.6 years STANDARD_DEVIATION 6.7 | 24.6 years STANDARD_DEVIATION 8 | 26.8 years STANDARD_DEVIATION 6.7 | 26.9 years STANDARD_DEVIATION 7.2 | 25.6 years STANDARD_DEVIATION 7.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 5 Participants | 8 Participants | 6 Participants | 7 Participants | 6 Participants | 8 Participants | 14 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 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 | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 8 Participants | 7 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 7 Participants | 12 Participants | 57 Participants |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 8 participants | 8 participants | 8 participants | 8 participants | 14 participants | 70 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 7 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 13 Participants | 67 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 14 |
| other Total, other adverse events | 1 / 8 | 2 / 8 | 2 / 8 | 0 / 8 | 1 / 8 | 1 / 8 | 2 / 8 | 1 / 14 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 14 |
Outcome results
Primary
Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose.
All adverse events, defined as any untoward medical occurrence regardless of its causal relationship to the study treatment, were collected for 14 days after dosing. The PI then determined relatedness to the study drug. Related was defined as there is a reasonable possibility that the study product caused the adverse event. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event.
Time frame: Within 14 Days of first dose
Population: All participants are included in the analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.5 mg/kg Oxfendazole | Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose. | 0 Participants |
| 1 mg/kg Oxfendazole | Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose. | 0 Participants |
| 3 mg/kg Oxfendazole | Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose. | 1 Participants |
| 7.5 mg/kg Oxfendazole | Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose. | 0 Participants |
| 15 mg/kg Oxfendazole | Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose. | 0 Participants |
| 30 mg/kg Oxfendazole | Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose. | 1 Participants |
| 60 mg/kg Oxfendazole | Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose. | 1 Participants |
| Placebo | Number of Subjects Reporting Adverse Events Related to Oxfendazole Within 14 Days of Receipt of a Single Oral Dose. | 1 Participants |
Secondary
Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole
AUC(0-infinity) was defined as the total area under the concentration-time curve from dosing (time 0) taken to the limit as the end time becomes arbitrarily large. AUC(0-infinity) and was calculated by adding AUC(0-last) to an extrapolated value equal to the last measured concentration greater than the lower limit of quantification of the bioanalytical assay divided by the terminal phase elimination rate constant (Ke) computed from concentrations that were measured using a validated HPLCMS/MS method
Time frame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
Population: All participants receiving oxfendazole are included in the analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg/kg Oxfendazole | Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole | 11682.4 ng•hr/mL | Geometric Coefficient of Variation 44.8 |
| 1 mg/kg Oxfendazole | Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole | 13117.7 ng•hr/mL | Geometric Coefficient of Variation 54.4 |
| 3 mg/kg Oxfendazole | Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole | 30803.1 ng•hr/mL | Geometric Coefficient of Variation 20.1 |
| 7.5 mg/kg Oxfendazole | Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole | 73928.9 ng•hr/mL | Geometric Coefficient of Variation 40.6 |
| 15 mg/kg Oxfendazole | Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole | 99542.6 ng•hr/mL | Geometric Coefficient of Variation 23.9 |
| 30 mg/kg Oxfendazole | Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole | 78344.0 ng•hr/mL | Geometric Coefficient of Variation 34.4 |
| 60 mg/kg Oxfendazole | Area Under the Concentration Time-curve From Time Zero to Infinity (AUC(0-infinity)) for Oxfendazole | 108618.2 ng•hr/mL | Geometric Coefficient of Variation 38.4 |
Secondary
Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma
Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations computed from concentrations that were measured using a validated HPLC-MS/MS method.
Time frame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
Population: All participants receiving oxfendazole are included in the analysis population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg/kg Oxfendazole | Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma | 943.9 ng/mL | Geometric Coefficient of Variation 28.4 |
| 1 mg/kg Oxfendazole | Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma | 1155.9 ng/mL | Geometric Coefficient of Variation 26.8 |
| 3 mg/kg Oxfendazole | Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma | 2436.9 ng/mL | Geometric Coefficient of Variation 24 |
| 7.5 mg/kg Oxfendazole | Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma | 4781.3 ng/mL | Geometric Coefficient of Variation 25.6 |
| 15 mg/kg Oxfendazole | Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma | 6254.8 ng/mL | Geometric Coefficient of Variation 21.7 |
| 30 mg/kg Oxfendazole | Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma | 5301.3 ng/mL | Geometric Coefficient of Variation 30.5 |
| 60 mg/kg Oxfendazole | Maximum Observed Concentration (Cmax) of Oxfendazole in Plasma | 6768.4 ng/mL | Geometric Coefficient of Variation 31.3 |
Secondary
Plasma Concentrations of Oxfendazole Fenbendazole
Concentrations of oxfendazole fenbendazole in plasma were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics.
Time frame: Day 1-Day15
Population: All participants receiving oxfendazole are included in the analysis population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 8 | 0.4 ng/mL | Standard Deviation 0.5 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 4 Hours | 0.6 ng/mL | Standard Deviation 1.8 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 15 | 0.4 ng/mL | Standard Deviation 0.5 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 4 | 0.4 ng/mL | Standard Deviation 0.5 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 1 Hour | 0 ng/mL | Standard Deviation 0 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 6 Hours | 0.5 ng/mL | Standard Deviation 1.3 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 6 | 0.4 ng/mL | Standard Deviation 0.5 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 2 Hours | 0 ng/mL | Standard Deviation 0 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 12 Hours | 0.3 ng/mL | Standard Deviation 0.9 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 10 Hours | 0.3 ng/mL | Standard Deviation 0.8 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 3 | 0.4 ng/mL | Standard Deviation 0.5 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 8 Hours | 0.3 ng/mL | Standard Deviation 0.9 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 24 Hours | 0.7 ng/mL | Standard Deviation 1 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 6 | 0.9 ng/mL | Standard Deviation 0.4 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 24 Hours | 2.3 ng/mL | Standard Deviation 1.6 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 12 Hours | 2.3 ng/mL | Standard Deviation 1.4 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 2 Hours | 0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 8 | 0.9 ng/mL | Standard Deviation 0.4 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 4 Hours | 0.8 ng/mL | Standard Deviation 1.1 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 1 Hour | 0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 6 Hours | 2.0 ng/mL | Standard Deviation 1.4 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 4 | 0.9 ng/mL | Standard Deviation 0.4 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 8 Hours | 1.9 ng/mL | Standard Deviation 1.2 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 15 | 0.9 ng/mL | Standard Deviation 0.4 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 3 | 0.9 ng/mL | Standard Deviation 0.4 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 10 Hours | 2.3 ng/mL | Standard Deviation 1.2 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 1 Hour | 0.3 ng/mL | Standard Deviation 0.8 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 4 Hours | 3.5 ng/mL | Standard Deviation 2.5 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 8 | 1.0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 2 Hours | 0.4 ng/mL | Standard Deviation 0.8 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 8 Hours | 5.2 ng/mL | Standard Deviation 2.9 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 12 Hours | 6.7 ng/mL | Standard Deviation 2.4 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 3 | 3.2 ng/mL | Standard Deviation 2.8 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 24 Hours | 7.1 ng/mL | Standard Deviation 2.5 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 6 | 1.0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 10 Hours | 6.8 ng/mL | Standard Deviation 2.6 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 6 Hours | 4.8 ng/mL | Standard Deviation 2.9 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 4 | 1.1 ng/mL | Standard Deviation 0.4 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 12 Hours | 10.1 ng/mL | Standard Deviation 5.5 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 1 Hour | 0.3 ng/mL | Standard Deviation 0.7 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 2 Hours | 1.1 ng/mL | Standard Deviation 1.5 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 4 Hours | 3.0 ng/mL | Standard Deviation 3.2 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 6 Hours | 6.6 ng/mL | Standard Deviation 4.8 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 8 Hours | 6.7 ng/mL | Standard Deviation 4.6 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 10 Hours | 10.0 ng/mL | Standard Deviation 5.7 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 24 Hours | 4.9 ng/mL | Standard Deviation 4 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 3 | 2.2 ng/mL | Standard Deviation 1.7 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 4 | 1.4 ng/mL | Standard Deviation 1 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 6 | 1.0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 8 | 1.0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 6 Hours | 9.9 ng/mL | Standard Deviation 8.3 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 6 | 1.0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 4 | 1.2 ng/mL | Standard Deviation 0.6 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 24 Hours | 10.0 ng/mL | Standard Deviation 3.7 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 4 Hours | 8.1 ng/mL | Standard Deviation 8 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 8 Hours | 10.8 ng/mL | Standard Deviation 8.3 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 1 Hour | 1.0 ng/mL | Standard Deviation 1.4 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 3 | 3.7 ng/mL | Standard Deviation 3.4 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 10 Hours | 11.2 ng/mL | Standard Deviation 6.6 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 8 | 1.0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 2 Hours | 2.6 ng/mL | Standard Deviation 2.5 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 12 Hours | 11.7 ng/mL | Standard Deviation 7.9 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 4 Hours | 4.4 ng/mL | Standard Deviation 4.3 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 24 Hours | 5.4 ng/mL | Standard Deviation 3.2 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 8 Hours | 5.0 ng/mL | Standard Deviation 5.1 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 3 | 2.5 ng/mL | Standard Deviation 3.1 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 6 Hours | 5.8 ng/mL | Standard Deviation 6.7 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 4 | 1.3 ng/mL | Standard Deviation 1.4 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 1 Hour | 1.4 ng/mL | Standard Deviation 1.2 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 6 | 0.9 ng/mL | Standard Deviation 0.4 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 2 Hours | 2.2 ng/mL | Standard Deviation 1.5 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 15 | 0.9 ng/mL | Standard Deviation 0.4 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 8 | 0.9 ng/mL | Standard Deviation 0.4 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 12 Hours | 6.4 ng/mL | Standard Deviation 4.5 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 10 Hours | 5.5 ng/mL | Standard Deviation 4.5 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 24 Hours | 16.7 ng/mL | Standard Deviation 12.9 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 6 Hours | 12.4 ng/mL | Standard Deviation 4.9 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 12 Hours | 20.9 ng/mL | Standard Deviation 19 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 3 | 5.5 ng/mL | Standard Deviation 4.2 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 10 Hours | 18.4 ng/mL | Standard Deviation 11.1 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 8 | 1.0 ng/mL | Standard Deviation 0 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 1 Hour | 5.9 ng/mL | Standard Deviation 2.4 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 4 Hours | 8.0 ng/mL | Standard Deviation 3.6 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 4 | 2.5 ng/mL | Standard Deviation 3 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 8 Hours | 15.5 ng/mL | Standard Deviation 8.6 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | Day 6 | 1.7 ng/mL | Standard Deviation 1.9 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Fenbendazole | 2 Hours | 6.3 ng/mL | Standard Deviation 2.5 |
Secondary
Plasma Concentrations of Oxfendazole Sulfone
Concentrations of oxfendazole sulfone in plasma were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics.
Time frame: Day 1-Day15
Population: All participants receiving oxfendazole are included in the analysis population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 12 Hours | 56.8 ng/mL | Standard Deviation 17.5 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 8 Hours | 59.7 ng/mL | Standard Deviation 13.7 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 10 Hours | 62.8 ng/mL | Standard Deviation 22.3 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 8 | 1.0 ng/mL | Standard Deviation 0 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 2 Hours | 48.7 ng/mL | Standard Deviation 9.3 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 6 | 1.2 ng/mL | Standard Deviation 0.4 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 4 | 3.6 ng/mL | Standard Deviation 3.1 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 4 Hours | 52.3 ng/mL | Standard Deviation 8.6 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 3 | 11.4 ng/mL | Standard Deviation 11.8 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 24 Hours | 30.9 ng/mL | Standard Deviation 23.4 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 6 Hours | 57.3 ng/mL | Standard Deviation 15.1 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 0.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 1 Hour | 28.5 ng/mL | Standard Deviation 4.6 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 24 Hours | 38.9 ng/mL | Standard Deviation 31.7 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 10 Hours | 70.7 ng/mL | Standard Deviation 28.5 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 6 Hours | 75.1 ng/mL | Standard Deviation 26.6 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 8 Hours | 78.2 ng/mL | Standard Deviation 27 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 8 | 1.0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 4 Hours | 67.6 ng/mL | Standard Deviation 16 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 3 | 11.1 ng/mL | Standard Deviation 10.3 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 2 Hours | 56.0 ng/mL | Standard Deviation 11.3 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 1 Hour | 31.1 ng/mL | Standard Deviation 11.1 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 6 | 1.3 ng/mL | Standard Deviation 1 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 12 Hours | 65.4 ng/mL | Standard Deviation 30.9 |
| 1 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 4 | 2.8 ng/mL | Standard Deviation 3.5 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 12 Hours | 111.4 ng/mL | Standard Deviation 12.4 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 1 Hour | 73.0 ng/mL | Standard Deviation 24.1 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 2 Hours | 106.3 ng/mL | Standard Deviation 31.5 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 4 Hours | 108.1 ng/mL | Standard Deviation 25.7 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 6 Hours | 113.8 ng/mL | Standard Deviation 26.2 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 8 Hours | 135.5 ng/mL | Standard Deviation 33.9 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 24 Hours | 68.5 ng/mL | Standard Deviation 21 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 10 Hours | 119.4 ng/mL | Standard Deviation 18.7 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 3 | 20.8 ng/mL | Standard Deviation 12.2 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 4 | 5.7 ng/mL | Standard Deviation 3.8 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 6 | 1.3 ng/mL | Standard Deviation 0.8 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 8 | 1.0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 24 Hours | 176.7 ng/mL | Standard Deviation 125.5 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 10 Hours | 308.7 ng/mL | Standard Deviation 120.1 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 3 | 64.8 ng/mL | Standard Deviation 94.9 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 1 Hour | 100.5 ng/mL | Standard Deviation 25.4 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 4 Hours | 223.8 ng/mL | Standard Deviation 62.5 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 6 Hours | 264.1 ng/mL | Standard Deviation 63 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 12 Hours | 296.0 ng/mL | Standard Deviation 90.3 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 8 Hours | 296.2 ng/mL | Standard Deviation 71.5 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 8 | 1.0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 6 | 6.4 ng/mL | Standard Deviation 10.2 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 2 Hours | 182.3 ng/mL | Standard Deviation 51.6 |
| 7.5 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 4 | 17.3 ng/mL | Standard Deviation 27.2 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 1 Hour | 111.6 ng/mL | Standard Deviation 51.9 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 10 Hours | 340.8 ng/mL | Standard Deviation 68.1 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 6 Hours | 308.3 ng/mL | Standard Deviation 98.8 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 12 Hours | 359.3 ng/mL | Standard Deviation 102.1 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 24 Hours | 261.8 ng/mL | Standard Deviation 83.4 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 4 Hours | 258.6 ng/mL | Standard Deviation 73 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 3 | 75.1 ng/mL | Standard Deviation 47.6 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 4 | 16.7 ng/mL | Standard Deviation 15.1 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 2 Hours | 219.2 ng/mL | Standard Deviation 73 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 6 | 1.2 ng/mL | Standard Deviation 0.6 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 8 | 1.0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 8 Hours | 336.8 ng/mL | Standard Deviation 72.2 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 2 Hours | 262.6 ng/mL | Standard Deviation 72.5 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 24 Hours | 185.2 ng/mL | Standard Deviation 90.5 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 4 Hours | 285.7 ng/mL | Standard Deviation 74.5 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 10 Hours | 352.4 ng/mL | Standard Deviation 106 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 4 | 17.2 ng/mL | Standard Deviation 23.6 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 8 Hours | 356.3 ng/mL | Standard Deviation 120.1 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 1 Hour | 161.5 ng/mL | Standard Deviation 41.3 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 12 Hours | 343.7 ng/mL | Standard Deviation 111.7 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 8 | 1.0 ng/mL | Standard Deviation 0 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 6 | 4.0 ng/mL | Standard Deviation 7.7 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 6 Hours | 330.3 ng/mL | Standard Deviation 90.1 |
| 30 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 3 | 57.5 ng/mL | Standard Deviation 54.4 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 15 | 1.0 ng/mL | Standard Deviation 0 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 2 Hours | 319.0 ng/mL | Standard Deviation 119.9 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 24 Hours | 362.2 ng/mL | Standard Deviation 222.7 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 6 Hours | 404.6 ng/mL | Standard Deviation 154.7 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 3 | 119.5 ng/mL | Standard Deviation 86.8 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 4 | 33.8 ng/mL | Standard Deviation 28.6 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 8 | 1.1 ng/mL | Standard Deviation 0.4 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 4 Hours | 345.4 ng/mL | Standard Deviation 133 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 8 Hours | 454.8 ng/mL | Standard Deviation 174 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 12 Hours | 487.7 ng/mL | Standard Deviation 210.3 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 10 Hours | 470.7 ng/mL | Standard Deviation 182.5 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | Day 6 | 6.6 ng/mL | Standard Deviation 9.4 |
| 60 mg/kg Oxfendazole | Plasma Concentrations of Oxfendazole Sulfone | 1 Hour | 209.1 ng/mL | Standard Deviation 84.5 |
Secondary
Terminal Elimination Half-life (t1/2) of Oxfendazole
The apparent terminal elimination half-life (t1/2) was defined as the time required for the drug concentration to decrease by a factor of one-half in the terminal phase computed from concentrations that were measured using a validated HPLCMS/MS method.
Time frame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
Population: All participants receiving oxfendazole are included in the analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5 mg/kg Oxfendazole | Terminal Elimination Half-life (t1/2) of Oxfendazole | 9.1 hours | Standard Deviation 27.5 |
| 1 mg/kg Oxfendazole | Terminal Elimination Half-life (t1/2) of Oxfendazole | 8.5 hours | Standard Deviation 25.3 |
| 3 mg/kg Oxfendazole | Terminal Elimination Half-life (t1/2) of Oxfendazole | 10.3 hours | Standard Deviation 35.7 |
| 7.5 mg/kg Oxfendazole | Terminal Elimination Half-life (t1/2) of Oxfendazole | 9.6 hours | Standard Deviation 34.2 |
| 15 mg/kg Oxfendazole | Terminal Elimination Half-life (t1/2) of Oxfendazole | 10.0 hours | Standard Deviation 21.8 |
| 30 mg/kg Oxfendazole | Terminal Elimination Half-life (t1/2) of Oxfendazole | 9.8 hours | Standard Deviation 33.7 |
| 60 mg/kg Oxfendazole | Terminal Elimination Half-life (t1/2) of Oxfendazole | 11.0 hours | Standard Deviation 44.5 |
Secondary
Time of Maximum Observed Concentration (Tmax) of Oxfendazole
Tmax was defined as the time at which the maximum concentration (Cmax) occurs in plasma computed from concentrations that were measured using a validated HPLCMS/MS method.
Time frame: 0, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 336 hours post-dose
Population: All participants receiving oxfendazole are included in the analysis population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.5 mg/kg Oxfendazole | Time of Maximum Observed Concentration (Tmax) of Oxfendazole | 2.0 hours |
| 1 mg/kg Oxfendazole | Time of Maximum Observed Concentration (Tmax) of Oxfendazole | 2.0 hours |
| 3 mg/kg Oxfendazole | Time of Maximum Observed Concentration (Tmax) of Oxfendazole | 2.0 hours |
| 7.5 mg/kg Oxfendazole | Time of Maximum Observed Concentration (Tmax) of Oxfendazole | 2.0 hours |
| 15 mg/kg Oxfendazole | Time of Maximum Observed Concentration (Tmax) of Oxfendazole | 2.0 hours |
| 30 mg/kg Oxfendazole | Time of Maximum Observed Concentration (Tmax) of Oxfendazole | 2.0 hours |
| 60 mg/kg Oxfendazole | Time of Maximum Observed Concentration (Tmax) of Oxfendazole | 2.0 hours |
Secondary
Urine Concentrations of Oxfendazole Fenbendazole
Concentrations of oxfendazole fenbendazole in urine were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics.
Time frame: Day 1-Day 15
Population: All participants receiving oxfendazole are included in the analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 48-60 hours | 0 ng/mL | Standard Deviation 0 |
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 4-8 hours | 0 ng/mL | Standard Deviation 0 |
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 12-24 hours | 0 ng/mL | Standard Deviation 0 |
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 0-4 hours | 0 ng/mL | Standard Deviation 0 |
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 8-12 hours | 0 ng/mL | Standard Deviation 0 |
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 24-32 hours | 0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 0-4 hours | 0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 12-24 hours | 0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 48-60 hours | 0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 4-8 hours | 0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 24-32 hours | 0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 8-12 hours | 0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 24-32 hours | 0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 8-12 hours | 0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 48-60 hours | 0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 12-24 hours | 0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 0-4 hours | 0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 4-8 hours | 0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 24-32 hours | 0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 0-4 hours | 0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 4-8 hours | 0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 8-12 hours | 0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 12-24 hours | 0 ng/mL | Standard Deviation 0 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 48-60 hours | 0.28 ng/mL | Standard Deviation 0.78 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 12-24 hours | 0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 4-8 hours | 0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 24-32 hours | 0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 48-60 hours | 0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 8-12 hours | 0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 0-4 hours | 0 ng/mL | Standard Deviation 0 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 8-12 hours | 0 ng/mL | Standard Deviation 0 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 12-24 hours | 0 ng/mL | Standard Deviation 0 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 4-8 hours | 0 ng/mL | Standard Deviation 0 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 24-32 hours | 0 ng/mL | Standard Deviation 0 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 0-4 hours | 0 ng/mL | Standard Deviation 0 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 48-60 hours | 0 ng/mL | Standard Deviation 0 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 8-12 hours | 0 ng/mL | Standard Deviation 0 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 4-8 hours | 0 ng/mL | Standard Deviation 0 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 48-60 hours | 0 ng/mL | Standard Deviation 0 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 12-24 hours | 0 ng/mL | Standard Deviation 0 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 24-32 hours | 0.03 ng/mL | Standard Deviation 0.07 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Fenbendazole | 0-4 hours | 0 ng/mL | Standard Deviation 0 |
Secondary
Urine Concentrations of Oxfendazole Sulfone
Concentrations of oxfendazole sulfone in urine were measured using a validated HPLCMS/MS method. Concentrations \<LLOQ (2 ng/mL) set to LLOQ/2 if after 1st =LLOQ concentration or 0 otherwise for calculating summary statistics.
Time frame: Day 1-Day 15
Population: All participants receiving oxfendazole are included in the analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 48-60 hours | 0 ng/mL | Standard Deviation 0 |
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 4-8 hours | 18.9 ng/mL | Standard Deviation 13.8 |
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 12-24 hours | 18.9 ng/mL | Standard Deviation 29.1 |
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 0-4 hours | 9.1 ng/mL | Standard Deviation 16.8 |
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 8-12 hours | 34.1 ng/mL | Standard Deviation 50.3 |
| 0.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 24-32 hours | 0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 0-4 hours | 4.1 ng/mL | Standard Deviation 11.6 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 12-24 hours | 26.3 ng/mL | Standard Deviation 33.7 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 48-60 hours | 0 ng/mL | Standard Deviation 0 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 4-8 hours | 24.9 ng/mL | Standard Deviation 18.3 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 24-32 hours | 0.9 ng/mL | Standard Deviation 2.6 |
| 1 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 8-12 hours | 26.5 ng/mL | Standard Deviation 22.9 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 24-32 hours | 1.2 ng/mL | Standard Deviation 3.4 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 8-12 hours | 30.3 ng/mL | Standard Deviation 14.7 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 48-60 hours | 0 ng/mL | Standard Deviation 0 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 12-24 hours | 15.8 ng/mL | Standard Deviation 18.5 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 0-4 hours | 19.9 ng/mL | Standard Deviation 25.7 |
| 3 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 4-8 hours | 38.2 ng/mL | Standard Deviation 20.3 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 24-32 hours | 3.2 ng/mL | Standard Deviation 4.9 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 0-4 hours | 45.6 ng/mL | Standard Deviation 37 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 4-8 hours | 86.0 ng/mL | Standard Deviation 68.9 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 8-12 hours | 76.0 ng/mL | Standard Deviation 60.1 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 12-24 hours | 100.4 ng/mL | Standard Deviation 87.2 |
| 7.5 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 48-60 hours | 0.8 ng/mL | Standard Deviation 1.6 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 12-24 hours | 91.8 ng/mL | Standard Deviation 46.7 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 4-8 hours | 88.1 ng/mL | Standard Deviation 27.6 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 24-32 hours | 7.5 ng/mL | Standard Deviation 9.1 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 48-60 hours | 0 ng/mL | Standard Deviation 0 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 8-12 hours | 92.3 ng/mL | Standard Deviation 33.3 |
| 15 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 0-4 hours | 46.4 ng/mL | Standard Deviation 20.9 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 8-12 hours | 99.7 ng/mL | Standard Deviation 40.8 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 12-24 hours | 69.9 ng/mL | Standard Deviation 49 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 4-8 hours | 105.8 ng/mL | Standard Deviation 36.4 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 24-32 hours | 18.2 ng/mL | Standard Deviation 32.4 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 0-4 hours | 68.0 ng/mL | Standard Deviation 21.2 |
| 30 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 48-60 hours | 7.3 ng/mL | Standard Deviation 9.7 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 8-12 hours | 92.9 ng/mL | Standard Deviation 39.7 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 4-8 hours | 124.1 ng/mL | Standard Deviation 72.8 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 48-60 hours | 5.3 ng/mL | Standard Deviation 7.3 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 12-24 hours | 139.0 ng/mL | Standard Deviation 137.7 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 24-32 hours | 26.1 ng/mL | Standard Deviation 32.4 |
| 60 mg/kg Oxfendazole | Urine Concentrations of Oxfendazole Sulfone | 0-4 hours | 64.5 ng/mL | Standard Deviation 44.5 |