Phase I Clinical Trials

• Phase I clinical trials should usually be carried out by investigators trained in clinical pharmacology and having the necessary facilities to closely observe and monitor the subjects.

• These may be carried out at one or two centers.

• At least 2 subjects should be used on each dose.

• The document required for Phase I Clinical Trials are,

  1. Systemic Toxicity studies

     • Single dose toxicity studies

     • Dose Ranging Studies

     • Repeat-dose systemic toxicity studies

1. 2. Male fertility study

   3. In-vitro genotoxicity tests

   4. Relevant local toxicity studies with proposed route of clinical application (duration depending on proposed length of clinical exposure)

   5. Allergenicity / Hypersensitivity tests (when there is a cause for concern or for parenteral drugs, including dermal application)

   6. Photo-allergy or dermal photo-toxicity test (if the drug or a metabolite is related to an authorized agent causing photosensitivity or the nature of action suggests such a potential)

In trials involving Medical Device India products, adherence to regulatory standards is critical, including compliance with Medical Device Registration requirements.

Phase II Clinical Trials

• Phase II clinical trials should normally be carried out on 10-12 patients at each dose level.

• These studies should usually be carried out at 3-4 centers by clinicians specialized on the concerned therapeutic areas and having adequate facilities to perform the necessary investigations for efficacy and safety.

• The document required for Phase II Clinical Trials are,

  1. Summary of all the non-clinical safety data (listed above) already submitted while obtaining the permissions for Phase I trial.

  2. In case of an application for directly starting a Phase II trial – complete details of the nonclinical safety data needed for obtaining the permission for Phase I trial, as per the list provided above must be submitted.

  3. Repeat-dose systemic toxicity studies of appropriate duration to support the duration of proposed human exposure.

  4. In-vivo genotoxicity tests

  5. Segment II reproductive/developmental toxicity study (if female patients of child bearing age are going to be involved)

Phase III Clinical Trials

• If the drug is already approved/marketed in other countries, phase III data should generally be obtained on at least 100 patients distributed over 3-4 centres. Medical Device India guidelines may also apply if the trial involves devices.

• If the drug is a new drug substance discovered in India and not marketed in any other country, phase III data should generally be obtained on at least 500 patients distributed over 10-15 centres.

• The document required for Phase II Clinical Trials are,

  1. For Phase III Clinical Trials Provide a summary of all the non-clinical safety data (listed above) already submitted while obtaining the permissions for Phase I and II trials, with appropriate references.

  2. In case of an application for directly initiating a Phase III trial – complete details of the non-clinical safety data needed for obtaining the permissions for Phase I and II trials, as per the list provided above must be provided. Appointing an authorized agent ensures regulatory compliance during this phase.

  3. Repeat-dose systemic toxicity studies of appropriate duration to support the duration of proposed human exposure.

  4. Reproductive/developmental toxicity studies

     • Segment I (if female patients of child bearing age are going to be involved), and

     • Segment III (for drugs to be given to pregnant or nursing mothers or where there are indications of possible adverse effects on foetal development)

  5. Carcinogenicity studies (when there is a cause for concern or when the drug is to be used for more than 6 months).

Phase IV Clinical Trial

Provide a summary of all the non-clinical safety data (listed above) already submitted while obtaining the permissions for Phase I, II and III trials, with appropriate references. Medical Device registration in India may require additional documentation, In case an application is made for initiating the Phase IV trial, complete details of the non-clinical safety data needed for obtaining the permissions for Phase I, II and III trials, as per the list provided above must be submitted. Ensuring Medical Device Registration standards during this phase is critical.

Permission to carry out these trials shall generally be given in stages, considering the data emerging from earlier Phase(s). CDSCO will initially examine such applications, if any particular data is lacking, the applicant will be informed  or else the applications will be forwarded to the members of IND committee in case of Investigational New Drugs (INDs) or to the members of New Drug Advisory Committee (NDAC) in case of new chemical entities other than IND. In such cases, appointing an authorized agent can facilitate smooth regulatory compliance.

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A per Clause 1(3) of Schedule Y to Drugs & Cosmetics Rules, for drugs indicated in life threatening / serious diseases or diseases of special relevance to the Indian health scenario, the toxicological & clinical data requirements may be abbreviated, deferred or omitted, as deemed appropriate by the Licensing Authority. There is as such neither any definition of “life threatening / serious diseases” nor any list of such disease/disorders prescribed under the Drugs & Cosmetics Act & Rules. Diseases like Cancer, AIDS etc are generally considered as Serious /Life Threatening Diseases.

To conduct clinical trials in India contact us at [email protected]