Poliomyelitis MedDRA version: 14.1 Level: HLT Classification code 10036017 Term: Poliomyelitis viral infections System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: V-073 200 mg
Product Code: V-073
Pharmaceutical Form: Capsule, hard
Current Sponsor code: V-073
Other descriptive name: V-073
Concentration unit: mg milligram(s)
Concentration type: equ
Sponsors
ViroDefense Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be a healthy, non-smoking male or female of any race, having received prior vaccination with inactivated polio vaccine, and at least 18 years old and no more than 50 years old, inclusively; 2. Have a body mass index (BMI) within the range of >18.5 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. A history of natural or OPV-derived poliovirus infection; 2. Female subjects who are pregnant, attempting to become pregnant or lactating; 3. Any disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, or gastrointestinal (including a gastric or duodenal ulcer) systems; 4. The presence of clinically significant abnormal laboratory values in the opinion of the Investigator or Sponsor; 5. A history of alcoholism or drug addiction within the past 2 years, recent use of any recreational drugs, or positive results from a urine screen for substances of abuse and alcohol at screening and admission; 6. A history of serious mental illness, that includes but is not limited to schizophrenia, bipolar disorder, or severe depression requiring hospitalization or pharmacological intervention; 7. Is a member of a household in which another member is known to be immunodeficient or is actively being treated for a malignancy, autoimmune disease or transplant; 8. A history of difficulty donating blood or inadequate venous access; 9. The donation of blood or plasma within 30 days prior to receiving study drug; 10. Lactose intolerant; 11. A positive hepatitis screen that tests for both hepatitis B surface antigen (HBsAg) and antibody to hepatitis C (HCV); 12. A positive test result for HIV antibody by enzyme immunoassay which is confirmed by Western immunoblot; 13. Receipt of an investigational drug or product, or participation in a drug study within a period of 30 days prior to receiving study drug (for investigational drugs with an elimination half-life greater than 10 days, this will be extended to 60 days); 14. Use of any drug or medication known to suppress/inhibit the immune system (e.g., steroids such as prednisone); 15. Use of a drug therapy known to induce or inhibit hepatic drug metabolism within 30 days prior to receiving study drug or during the study. 16. Use of any prescription or over-the-counter (OTC) drug therapy, excluding paracetamol and including herbal, homeopathic, vitamins, minerals and nutritional supplements, unapproved by the Sponsor, within 2 weeks prior to receiving the study drug (for drugs with an elimination half-life greater than 10 days, this will be extended to 60 days). 17. Use of grapefruits and grapefruit-containing juices within 1 week prior to dosing. 18. Unable to follow the restrictions outlined in the protocol ; or judgment by the PI that the subject should not participate in the study;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: · To determine the effect of V-073 and placebo treatment on poliovirus serotype 1 excretion in the stool after administration of mOPV1 as determined by virus culture; · To evaluate the safety and tolerability of multiple oral doses of V-073 administered to healthy volunteers;;Secondary Objective: · To evaluate the pharmacokinetics profile of V-073 after administration of multiple oral doses; · To determine the duration of poliovirus excretion in V-073 and placebo treated subjects; · To determine the levels of poliovirus excretion over time with V-073 or placebo treatment; · To compare the effectiveness of V-073 on poliovirus excretion when administered afterconsumption of a standard and high fat meal; · To determine the initial and post-V-073 treatment susceptibility of excreted poliovirus to V-073; · To determine the poliovirus-specific serum IgA and serum neutralizing (SN) antibody levels before and after treatment with V-073.;Primary end point(s): Pharmacokinetics: • The primary pharmacokinetic measure will be the single and multiple dose plasma pharmacokinetics of V-073 Pharmacodynamics: • Stool samples will be assessed for virus both qualitatively and quantitatively in a virusinduced cytopathic effect cell culture assay. • Stool samples may be assessed for virus qualitatively using poliovirus specific RT-PCR methodology.;Timepoint(s) of evaluation of this end point: Pharmacokinetics: • The primary pharmacokinetic measure will be the single and multiple dose plasma pharmacokinetics of V-073; • Pharmacokinetic parameters for Day 3 and Day 16 QD dosing will include Cmax, tmax, C24,AUC(0-tau),; • Cmin (trough) levels of V-073 will be determined by analyzing plasma samples collected prior to the morning dose on Days 4-16, and 24h after the last dose. Pharmacodynamics: The resulting virology data will be analyzed for the following endpoints - Time to virus excretion negativity for chloroform extracted samples. -Time to virus excretion negativity f | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Drug Susceptibility Group 1 to 4, Group 7 and 8: Virus from each subject's virus culture positive chloroform-extracted stool sample on Day 3 (or Day 2 if Day 3 sample is not available; pretreatment) and their last virus culture positive stool sample will be assessed for susceptibility to V-073 in a cell culture virus-induced cytopathic effect assay (EC50 determination). Virus samples with reduced drug susceptibility (defined as a >20-fold increase in EC50 value relative to the corresponding Day 3 [pretreatment] susceptibility) will be sequenced across the VP3 and VP1 protein coding regions to determine the genetic basis for reduced drug susceptibility. Safety: Safety and tolerability will be assessed by monitoring adverse experiences, measuring vital signs, electrocardiograms (ECGs), assessment of clinical laboratory determinations from blood samples, and performance of physical examinations Group 5 and 6: Drug Susceptibility: Virus from each subject’s virus culture positive chloroform-extracted stool sample on Day 1 (or Day 0 if Day 1 sample is not available; pretreatment) and their last virus culture positive stool sample will be assessed for susceptibility to V-073 in a cell culture virus-induced cytopathic effect assay (EC50 determination). Virus samples with reduced drug susceptibility (defined as a >20-fold increase in EC50 value relative to the corresponding Day 1 [pretreatment] susceptibility) will be sequenced across the VP3 and VP1 protein coding regions to determine the genetic basis for reduced drug susceptibility. Safety: Safety and tolerability will be assessed by monitoring adverse experiences, measuring vital signs, electrocardiograms (ECGs), assessment of clinical laboratory determinations from blood samples, and performance of physical examinations;Timepoint(s) of evaluation of this end point: Drug Susceptibility: Group 1 to 4, Group 7 and 8 Day 3 (or Day 2 if Day 3 sample is not available; pretreatment) and | — |
Countries
Sweden
Contacts
Public ContactDr Marc S. Collett
ViroDefense Inc
Outcome results
None listed