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Phase-1 Clinical trials

12 May 2020

Phase-1 clinical trials is entirely different from other studies  and the first step in the development of New Chemical entity . It requires perfect understanding of preclinical studies and its correct use for human beings in identifying the dosages, drug administration and the safety.  Based on this studies, the future studies can be carried out.

There are many studies which could be included in Phase-1 studies. Some of them are mentioned as below:

1. First in Man studies: It is for the first time a new drug is being administered in the human beings. It provided an idea about the safety of molecule and PK characteristics (Absorption, Distribution, Metabolism, elimination) of the drug in human being. This study is by and large conducted in the Healthy male subjects as a cohort of 5-10 subjects.
2. Single Ascending Dose (SAD) studies: This study is by and large conducted in the Healthy subjects as a cohort of 6 to 12 subjects. In each cohort there could be some subjects receiving active drug and very few receive placebo (e.g. 5 Active drug+1 Placebo, 7 Active drug + 1 Placebo, 8 Active drug+ 2 Placebo, 10 Active drug+ 2 Placebo etc.). There may be 4 to 6 cohorts in the study. Each cohort receives a Dose of the New Drug in the Ascending fashion. The PK samples are collected at various time intervals to understand the PK profile of the NCE and difference between each dose. Sometimes, PD parameters are also used to understand the profile of the drug at different dosage and to evaluate the safety. One of the cohort will be designed to evaluate food effect of particular molecule, in which drug will be administered after 30 minutes of high fat high calorie breakfast consumption by subject. Evaluation will be done by comparison of safety, PK and PD data in fasting and fed condition.

Occasionally, First In Man studies are carried out in patients particularly if the drug is for Oncology { Cytotoxic ). For AIDs, etc.

1. Multiple Ascending Dose (MAD) studies: One of the safe and effective dose will be selected from SAD study of particular molecule based on all available data. There may be 4 to 6 cohorts in the study. Each cohort receives multiple dose for 7-28 days depending upon characteristics of molecule. Dose of the Drug in each cohort will be in the Ascending fashion. It will be useful to evaluate accumulation of molecule and its effect in human body. There is a trend to select patients in one of the cohort to get an early idea about safety and efficacy in patients.
2. Drug interaction studies: There are many molecules which affect the metabolism of other drugs. So, it is important to determine the extent of effect of molecule to interact with other drugs and magnitude of its effect to consider it as safe and effective. Depending upon characteristics of IND molecule, drug which inhibit the metabolism of IND molecule or drug which induce the metabolism of IND molecule will be selected to conduct drug-drug interaction studies. Metabolism of some molecules significantly affected by different kind of food (e.g. high fat, standard fat, low fat, fasting). Therefore, Food-drug interaction studies also require to evaluate the extent and magnitude of food effect.
3. Vaccine studies: It is special kind of studies which does not include PK profile and require immunogenicity or other kind of biomarkers to evaluate the efficacy of vaccine.  The local and systemic adverse events are also evaluated.
4. Bio-similar PK-PD studies: It is unique type of studies, which evaluate the Safety, PK profile, Pharmacodynamic and Immunogenicity assessment by different kind of markers.
5. Thorough QT (TQT) studies: This is mainly required for drugs or members of chemical or pharmacological class that have been found to be associated with QT/QTc interval prolongation. It is intended to determine whether the drug has as threshold pharmacologic effect on cardiac repolarization.
6. Age and Gender study. The drug may behave differently in male or female genders. It can also behave differently in elderly population or even in menopausal women.

Lambda has a specially designed Phase-1 unit where such studies are being conducted. Dedicated state-of-the-art Phase-I units in Ahmedabad (India), Toronto (Canada) & Novum (USA) enable us to have a synergistic approach across geographies for timeline and cost advantages. Till date, Lambda has successfully executed over 43 phase-1 studies in the last 5 years for various formulations including Oral, Parenteral, Inhalers, Topical, Transdermal, Nasal Sprays, Injectables, Pessaries, Suppositories, etc.