|
CRITERIA
|
OPERATIONAL DEFINITION
|
| Scientific Rationale |
1) Consistency of pre-clinical data in different settings and HD animal models (e,g, fragment and full length)
2) Credible mechanism/target relevant to HD although exact mechanism may be unclear
|
| Kinetics and Blood-brain barrier (BBB) penetration |
Evidence by direct experiments or inference that BBB penetration occurs and that adequate concentration of agent can be achieved with the intended route of administration. Extrapolations from animal model to human dose should be explicitly stated.
|
| Safety and Tolerability (including drug interactions) |
Phase I study: adequate pre-clinical toxicology data to merit an Investigational New Drug Application (IND).
Phase II/III study: Preliminary data show agent is safe and tolerable in humans in the dose and route of administration needed for the proposed effect (at least phase I data). No further safety data required before use in HD clinical trials.
|
|
Efficacy
1) demonstrated in relevant animal models of disease
or
2) indicated in human clinical studies
|
1) Animal: Two or more independent studies demonstrate efficacy in rodent models. Efficacy indicated by increase in survival and/or by behavioral changes and supported by changes in pathology. Evidence of dose response is supportive.
2) Human: Evidence from previous trials or observational data that is suggestive of a beneficial effect. Observational data should at least approximate criteria for causal inference.
|