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Once a drug / device is tested in the lab
and/or on animals, the data is submitted to the regulatory
authority to get approval for performing Clinical Trial. This is
called IND (Investigational New Drug) filing, the study
substance is termed as IMP (Investigational Medicinal
Product).
Phase 1 clinical trials are done to
demonstrate that the experimental
medication or treatment is safe for humans and to determine the
safest dose of a drug and to determine the best route of
administration i.e. how the drug should be given (e.g. whether
to be swallowed orally / or to be injected intravenously / or to
be injected intramuscularly). Other areas of Phase 1 study
include pharmacokinetics (absorption, distribution, metabolism and
excretion) and pharmacodynamics. Multiple Phase 1 studies may be
required to demonstrate the safety of the IMP, It should be
understood that a single Phase 1 trial may not allow the drug to
advance to the next level (Phase 2). A phase 1 clinical trial usually
requires a small number of people (subjects) usually less
than 100. Most phase 1
trials are done in normal healthy subjects but some phase 1 studies are done only in patients
with the target disease e.g. Cancer patients (Target disease is the disease for which the IMP is being
developed. For safety and ethical reasons patients may be used for
example as in cases of cancer or HIV patents with advanced
disease may had all the existing treatment available to them. Due
consideration of the risk-benefit ratio is done when patients are
recruited in Phase 1 studies as patents may
benefit from the new treatment in the trial, but there are chances
that many patients won't benefit from the trail
Given below are some example cases of Phase 1 studies: (Source
www.clinicaltrail.gov)
 Study in patients of small cell cancer to estimate the MTD
(maximum tolerated dose) at a dose level up to 50 mg/day
A dose escalation study to determine the MTD and the dose limiting
toxicities of 'XXX drug' in subjects of Chronic Idiopathic
Myelofibrosis
Trial of 'XXX' Hookworm
vaccine in normal Brazilian Adults.
Safety and Tolerability Study of 'XXX' in Healthy Subjects
Subjects are recruited very slowly onto phase 1 trials. The first
group of subjects to take part are given a very small dose of the drug. If all goes well,
the next group have a slightly higher dose. The dose is gradually
increased with each group. The researchers monitor the effect of the
drug, until they find the best dose to give. This is called a dose
escalation study phase 1 study.
Phase I trials are usually conducted with open label, i.e. the
subjects are aware of the drugs that they are being given. Subjects are monitored closely to check their
tolerance of the drug and incidents of side effects. Depending on
the study, samples of blood, urine or stool and other physiological
information may be obtained for analysis to
evaluate absorption, distribution, metabolism and elimination of the
drug in the body. Other observations about how the subject feels
(e.g. pain, headache, fever, malaise and irritability), and vital
signs (blood pressure, heart rate) and behavioral matters are taken
into account. Depending on the complexity of the trial, the trial may last from several
months to a year and may cost few millions. If a treatment appears safe at the end of a phase 1 clinical
trial, it may then enter a phase 2 clinical trial.
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