Toxicity
Conditions
Brief summary
This Phase I evaluation of N-MCT in normal volunteers requires sequentially increased doses. At each dose level, the safety and pharmacokinetic will be measured. This Phase I trial will have the dose range of N-MCT from 200mg - 1200mg per patient.
Detailed description
This is a Phase 1 trial evaluating the safety and pharmacokinetics of N-MCT administered orally as a single ascending dose. Healthy male and female (non-pregnant, non-lactating) subjects ages 18-45, will be consented and allowed to participate in the study if upon screening they meet the inclusion / exclusion criteria. Subjects will be enrolled into one of four cohort groups sequentially. Each of the six subjects in each group will receive doses sequentially within 48 hours between each dose increase (ie, the second subject in a group will not receive a dose until 48 hours after the first subject received a dose). Cohort 1 (6 subjects, male & female) will receive 200 mg, Cohort 2 (6 subjects, male & female) will receive 400 mg, Cohort 3 (8 subjects, males and females, 2 placebo, 6 treated) will receive 800 mg and Cohort 4 (8 subjects, males and females, 2 placebo, 6 treated) will receive 1200 mg of N-MCT. Each cohort will be completed and the safety data evaluated prior to initiating the next cohort. All subjects will have plasma and urine samples evaluated for N-MCT. The PI of the protocol and the IDMC will review safety data (AEs), safety labs, vital signs, and findings through Day 7 for Cohort 1 before enrolling subjects in Cohort 2. Cohort 2 data through Day 7 will be reviewed accordingly by the PI and IDMC before enrolling subjects in Cohort 3. Cohort 3 data through Day 7 will be reviewed by the PI and the IDMC before enrolling subjects in Cohort 4. However, prior to dose escalation to a new cohort as described above, GHUCCTS IRB will review and approve, in expedited review, the IDMC report upon which the decision to escalate the dose to a new cohort is based.
Interventions
DRUGN-Methanocarbathymidine
Patients will receive 200 mg, 400 mg, 800 mg or 1200 mg of N-Methanocarbathymidine administered orally on day 1 after subject's full screen for each cohort. Each dose will be completely evaluated for safety and pharmacokinetics. The doses of each cohort will be given after complete evaluation of the preceding cohort for any sign of toxicity. In the absence of no observed toxicity, the next cohort will be started in the normal subjects.
OTHERPlacebo Capsule
Two patients in Cohort 3 & 4 will receive placebo capsules which is mannitol filled into size 0 capsules.
Sponsors
N&N Pharmaceuticals Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must meet all Inclusion Criteria to be included in the study: 1. Healthy men and women 18 to 45 years of age, inclusive 2. Ability to understand the consent process and study procedures 3. Informed consent obtained and signed 4. Comprehension of the protocol, as determined by the clinic personnel using a series of questions after explaining the procedures. 5. Subjects agree to be available for all study visits. 6. General good health, no current medical illness or clinically significant abnormal physical examination findings as determined by study physician investigators 7. Negative past or current history of herpes virus infections, or no current use of antiviral medications for the treatment of herpes virus infections 8. Negative serum pregnancy test at screening and a negative serum pregnancy test on the day of admission to the inpatient phase for all female subjects of child bearing potential. 9. Negative urine toxicology screen for marijuana, cocaine, opiates, amphetamines, phencyclidine, benzodiazepines, and barbiturates for screening and on the day of admission to the inpatient phase. 10. Negative urine toxicology screen for nicotine (Cotinine) for screening and on the day of admission to the inpatient phase. 11. Negative breath alcohol screen and agreement not to consume alcohol for the duration of the study. 12. Body mass index (BMI) greater than or equal to 18.5 kg/m2 and less than or equal to 29.9 kg/m2 \[weight (kg)\]/ \[height (m)2\]. 13. Agreement by subjects with reproductive potential to use highly effective contraception as described in protocol Section 4.1.1. 14. Willingness to avoid strenuous exercise for at least 72 hours prior to initial study drug administration and during the study to Day 7 visit. Note: Strenuous physical exercise includes long distance running \> 5 km/day, weight lifting, or any physical activity to which the subject is not accustomed.
Exclusion criteria
* Subjects meeting any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Safety and Tolerability of N-MCT Evaluated By The Sequential Review of Reported Adverse Events (AEs) and Changes from Baseline in Findings on Physical Examination, Vital Sign Measurements, and Safety Laboratory Tests | Day 1- Day 7 | The type, incidence, severity and relatedness to study drug of adverse events (AEs), and of abnormal findings on physical examination, vital sign measurements, and of safety laboratory tests (hematology, biochemistry, urinalysis) throughout the study period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentrations of N-MCT Measured Before and at Multiple Time Points After Oral administration | Pre-Dose (0.000), 0.250, 0.500,0.750, 1.000, 1.500, 2.000, 2.500, 3.000, 4.000, 6.000, 8.000, 12.000, 24.000 and 48.000 hours | Plasma levels of N-MCT will be measured before and at multiple time points after the oral administration. Plasma drug concentrations will be obtained at the following time points: pre-dose (0.000), 0.250, 0.500,0.750, 1.000, 1.500, 2.000, 2.500, 3.000, 4.000, 6.000, 8.000, 12.000, 24.000 and 48.000 hours. |
| Urine Concentrations of N-MCT Measured Before and at Multiple Time Points | 0 - 4, 4 - 8, 8 - 12, and 12 - 24 hours post dose | Urine concentrations of N-MCT will be measured before and at multiple time points after the oral administration. Pooled urine samples for the measurement of N-MCT concentration will be collected over the following intervals: 0 - 4, 4 - 8, 8 - 12, and 12 - 24 hours post dose. |
Countries
United States
Outcome results
None listed