Multiple Ascending Dose Study of Oxfendazole in Healthy Adult Volunteers
Condition: Helminthic Infection
MeSH terms: Helminthiasis
Study type: Interventional
Phase: Phase 1

Summary: 
      This Phase I study is an open label multiple ascending dose evaluation of the safety and PK
      of oxfendazole (3, 7.5, or 15 mg/kg) given orally daily to healthy adult men and nonpregnant
      women aged 18-45 followed by a single dose cross over trial evaluating the safety and
      pharmacokinetics of a single dose of oxfendazole (3 mg/kg) given following an 8 hour fast or
      following a high fat meal. The study duration will be approximately 12 months with each
      subject participation lasting approximately 6 weeks. In the multiple ascending dose
      evaluation, between 8 and 24 subjects will be enrolled; each dose group will be comprised of
      eight volunteers. To enhance safety, one sentinel subject will be dosed for five days and
      monitored for 7 days from the time of the first dose for predefined adverse events. If there
      are no predefined safety events, a second sentinel subject will be enrolled and followed for
      a total of 7 days. If there are no predefined safety signals identified for either of these
      two sentinel subjects, the remaining subjects in the group will be enrolled. After all eight
      subjects have completed the 10 day follow up period, an electronic safety review of the
      electronic data will be performed. If none of the predefined safety events have occurred DMID
      will approve enrollment into the second dose group (7.5 mg/kg oxfendazole daily x 5 days) and
      will be monitored for a total of 7 days each for predefined adverse events prior to enrolling
      the remaining subjects in the group. After the 10 day follow up period has been completed for
      group 2, an electronic safety review will be completed and if no predefined events have
      occurred two sequential subjects (one at a time with 7 days between each subject) will be
      enrolled into the third dose group (15 mg/kg oxfendazole daily x 5 days) and will be
      monitored for a total of 7 days each for predefined safety events prior to enrolling the
      remaining subjects in the group. In the food effects evaluation, 12 subjects will be enrolled
      into the single dose cross over group where half of the subjects will initially receive a
      single dose of 3 mg/kg of oxfendazole following an 8 hour fast and the other half will
      receive a single dose of 3 mg/kg of oxfendazole following a high fat meal. Subjects will then
      cross over to receive a single dose following a high fat breakfast or fasting period (water
      is permitted). All subjects will have received a dose of oxfendazole following both a fasting
      period and a meal. The primary objectives are: 1) To assess the safety of oxfendazole
      administered daily for five days; and 2) To assess the safety of oxfendazole administered as
      a single dose with or without food.
    

Detailed description: 
      This Phase I study is an open label multiple ascending dose evaluation of the safety and PK
      of oxfendazole (3, 7.5, or 15 mg/kg) given orally daily to healthy adult men and nonpregnant
      women aged 18-45 followed by a single dose cross over trial evaluating the safety and
      pharmacokinetics of a single dose of oxfendazole (3 mg/kg) given following an 8 hour fast or
      following a high fat meal. The study duration will be approximately 12 months with each
      subject participation lasting approximately 6 weeks. In the multiple ascending dose
      evaluation, between 8 and 24 subjects will be enrolled; each dose group will be comprised of
      eight volunteers. To enhance safety, one sentinel subject will be dosed for five days and
      monitored for 7 days from the time of the first dose for predefined adverse events. If there
      are no predefined safety events, a second sentinel subject will be enrolled and followed for
      a total of 7 days. If there are no predefined safety signals identified for either of these
      two sentinel subjects, the remaining subjects in the group will be enrolled. After all eight
      subjects have completed the 10 day follow up period, an electronic safety review of the
      electronic data will be performed. If none of the predefined safety events have occurred DMID
      will approve enrollment into the second dose group (7.5 mg/kg oxfendazole daily x 5 days) and
      will be monitored for a total of 7 days each for predefined adverse events prior to enrolling
      the remaining subjects in the group. After the 10 day follow up period has been completed for
      group 2, an electronic safety review will be completed and if no predefined events have
      occurred two sequential subjects (one at a time with 7 days between each subject) will be
      enrolled into the third dose group (15 mg/kg oxfendazole daily x 5 days) and will be
      monitored for a total of 7 days each for predefined safety events prior to enrolling the
      remaining subjects in the group. In the food effects evaluation, 12 subjects will be enrolled
      into the single dose cross over group where half of the subjects will initially receive a
      single dose of 3 mg/kg of oxfendazole following an 8 hour fast and the other half will
      receive a single dose of 3 mg/kg of oxfendazole following a high fat meal. Subjects will then
      cross over to receive a single dose following a high fat breakfast or fasting period (water
      is permitted). All subjects will have received a dose of oxfendazole following both a fasting
      period and a meal. The primary objectives are: 1) To assess the safety of oxfendazole
      administered daily for five days; and 2) To assess the safety of oxfendazole administered as
      a single dose with or without food. The secondary objectives are: 1) To define the multi-dose
      kinetics of oxfendazole; and 2) To determine the effect of food on the kinetics of
      oxfendazole.
    

Intervention name(s): Oxfendazole
Intervention type(s): Drug
Intervention description(s): methyl-5 (6)-phenylsulfiyl-2-benzimidazole carbamate, is a broad spectrum benzimidazole antihelminthic. It is the sulphoxide metabolite of fenbendazole.
Intervention MeSH terms: Oxfendazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Helminths; Oxfendazole; Pharmacokinetics; Safety