Phase 2a vs Phase 2b trials: Differences and comparison

Phase 2a vs Phase 2b trials:

Comparison of phase 2a vs phase 2b trials explained here. Phase 2 trials also known as therapeutic exploratory trials conducted in 100 to 300 patients approximately. As you already know, It explores the drug/device efficacy and evaluates the further safety. From this phase, Investigational drug testing will be done on target disease patients with the support of safety data from phase 1 clinical trials.

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Phase 2 trials conducted in well designed patient population with target disease. Sometimes phase 2 trials divided into to phase 2A and phase 2B trials. Even though both phases conducted to test the drug efficacy with further safety, types of studies conducted are different for each phase. That is Phase 2A trials known as early phase 2 trials, conducted with pharmaco-dynamics and clinical efficacy as primary end point.  These are the non-pivotal pilot studies to know the drug mechanism of action and how the drug affecting the body to show the efficacy. Phase 2B trails known as late phase 2 trials conducted to test the drug efficacy.

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Phase 2a trials:

Phase 2a trails are critical and most important trials in clinical development of a new drug. Because important decisions taken here for proceeding the further drug development. Proof of concept (PoC) studies done here. No efficacy data is not available in humans till this trails. Most of the drugs, efficacy wise perform well in animals and in non-clinical models but fail to show efficacy in the humans. So Phase 2a trials are critical. Usually Proof of concept studies conducted with two treatment groups, one group with test drug other group with placebo. First of all new drug is tested with a dose of Maximal tolerated dose (MTD) or a dose a bit lower than the MTD. The selected dose in this phase is as high as possible up to MTD, because to know the best possible efficacy. If the drug showing promising efficacy in humans with target disease, based on this proven concept, further trials will be conducted. If no promising effect observed in this trial, sponsor may stop the investments and man force for this drug tested drug. Further trials will be stopped. (Phase 2a vs Phase 2b trials continuation…)

Phase 2a vs phase 2b

Phase 2a vs Phase 2b clinical trials

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Phase 2b trials:

Based on proven efficacy from the early phase 2 trials, phase 2b trials conducted. Dose ranging studies starts here. Now they know the efficacy of a new drug at high dose but they do not the efficacy of other doses that are lower than the actual effect produced dose. So dose response studies conducted in this phase. Now the question is, which doses should be selected as test doses other than actual effect produced dose (MTD).

Different methods used to select the test doses like equal dose phasing or log dose spacing or using Fibonacci series or by other suggested approaches etc. For example effect produced high dose in phase 2a trial is 900mg. By using equal dose spacing method, calculated medium and low dose will be 600 mg and 300 mg respectively. If we use log dose spacing for high dose 900 mg we will get medium and low dose as 600 mg and 100 mg respectively. In groups new drug doses tested with placebo group. Along with these methods some other approaches are also used.

Simply we can say that phase 2a trials mainly all about proof of concept studies with Maximal tolerated dose (MTD) or a little bit lower dose. Phase 2b all about dose ranging or dose response studies with selected doses as explained above.  

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Clinical trials overview

Clinical trials all about conducting clinical research about new drug or device in humans. Every objective of the each phase of clinical trial is different from each other. Before getting into the clinical research in the humans, a lot of laboratory research already completed from the previous time that is preclinical research involving animals.

It is a complete step by step process like a constructing a building by using bricks and cement. Here bricks and cement are scientifically generated proofs. All procedures conducted according to the guidelines and accepted methods with prior approvals. Produces scientifically accepted proof to proceed for further research.

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 Clinical trials are divided into four phases. Four phases are as follows.

Phase I :

This is the first phase of human clinical trials. Some times Phase 0 (micro dosing) studies are also considered as first phase in human trails. Phase 0 trials not mandatory for all kinds of studies. But it helps to take the decision to proceed for further trials or not.

Usually phase I trials conducted in healthy population except for few diseases like HIV and cancer. It assess the new drug safety. 20-100 healthy volunteers tested for few months in this phase. Drug Pharmacokinetics tested here like how the drug affecting the body by knowing absorption, distribution, metabolism and excretion. Along with pharmacokinetics, it finds what are the side effects of the drug if dose level increased. Usually Seventy percentage of molecules can successfully complete this phase.

clinical trials overview
Phase II:

 This is the second phase of human clinical trials. It studies the drug efficacy. From this phase testing will be done on patients. Usually hundreds of patients tested for few months to two years in this phase. Number of patients used in this phase depends upon required statistical sample size calculation. Experimental drug efficacy compared with either standard drug or placebo. Relative experimental drug safety and efficacy compared by using double blind study designs. After entering drugs into the phase II, 30-40% molecules can successfully complete this phase.

Phase III:

It studies the effectiveness of a drug. It is a very large scale testing involves several thousands of patients tested for up to several years. Thorough information of a drug observed here including adverse effects from various study designs and testing procedures. Once this phase successfully completed, research company can request for the regulatory authorities for drug marketing approval After entering the drug into phase III, 50-60% molecules can successfully complete this phase.

Phase IV:

 This phase starts after drug approval for sale. This phase includes post marketing surveillance trails. Different types of findings observed about a drug in this phase like rare adverse reactions, drug interactions, long term safety, effectiveness and effect on patients quality of life, cost effectiveness with other therapies. Depend upon these findings, the regulatory authorities may recall or restrict the use or continues the drug in the market.

For example: Vioxx (Rofecoxib) is a nonsteroidal anti-inflammatory drug manufactured from Merck limited for pain relief. It was in the market for about 5.3 years. Due to findings in Phase IV like increased risk for heart attack and stroke, It was recalled from the market by FDA in 2004.

Zelnorm (Tegaserod maleate), a Novartis product indicated for irritable bowel syndrome with constipation in women younger than 55. Zolnorm also in the market for about 4.6 years in the market. Recalled by FDA in 2007 with a similar findings in Phase IV trials.

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