Phase-I Clinical Trial

A Phase-I Clinical Trial is an uncontrolled interventional clinical study that assesses a investigational medical intervention's clinical safety.

• AKA: Phase 1 Clinical Trial, First-In-Human Clinical Trial.
• Context:
  • It can (typically) be considered a human clinical trial's first learning phase.
  • It can (typically) be used to identify tolerable doses and to collect data on drug metabolism, excretion, and toxicity.
  • It can (typically) be an Uncontrolled Clinical Trial.
  • It can (often) involves 20-100 clinical trial participants.
  • It can range from being Single Ascending Dose (Phase Ia) Clinical Trial to being a Multiple Ascending Dose (Phase Ib) Clinical Trial.
  • …
• Example(s):
  • NCT04368728: Phase 1/2/3 Clinical Trial - RNA Vaccine Candidates (COVID-19),
  • …
• Counter-Example(s):
  • Preclinical Trial,
  • Phase-0 Clinical Trial,
  • Phase-II Clinical Trial,
  • Phase-III Clinical Trial,
  • Phase-IV Clinical Trial,
• See: Parallel Clinical Trial, Factorial Clinical Trial, Large-Simple Clinical Trial, Adaptive Clinical Trial.

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References

2021a

• (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Glossary_of_clinical_research#P Retrieved: 2022-01-11.
  • QUOTE: Phase I clinical trials
    • The first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection) and the best dose. The dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments. (NCI)
    • Initial studies to determine the metabolism and pharmacologic actions of drugs in humans, the side effects associated with increasing doses, and to gain early evidence of effectiveness; may include healthy participants and/or patients. (NLM)
    • Phase 1 includes the initial introduction of an investigational new drug into humans. Phase 1 studies are typically closely monitored and may be conducted in patients or normal volunteer subjects. These studies are designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. During Phase 1, sufficient information about the drug's pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid, Phase 2 studies. The total number of subjects and patients included in Phase 1 studies varies with the drug, but is generally in the range of 20 to 80. Phase 1 studies also include studies of drug metabolism, structure-activity relationships, and mechanism of action in humans, as well as studies in which investigational drugs are used as research tools to explore biological phenomena or disease processes. (21CFR312)
  • Phase I/II trial
    • A trial to study the safety, dosage levels, and response to a new treatment. (NCI)

2021b

• (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Phases_of_clinical_research#Phase_I Retrieved 2022-01-11.
  • QUOTE: Phase I trials were formerly referred to as “first-in-man studies” but the field generally moved to the gender-neutral language phrase "first-in-humans" in the 1990s; these trials are the first stage of testing in human subjects. They are designed to test the safety, side effects, best dose, and formulation method for the drug.

    Normally, a small group of 20–100 healthy volunteers will be recruited. These trials are often conducted in a clinical trial clinic, where the subject can be observed by full-time staff. These clinical trial clinics are often run by contract research organization (CROs) who conduct these studies on behalf of pharmaceutical companies or other research investigators. The subject who receives the drug is usually observed until several half-lives of the drug have passed. This phase is designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. Phase I trials normally include dose-ranging, also called dose escalation studies, so that the best and safest dose can be found and to discover the point at which a compound is too poisonous to administer. The tested range of doses will usually be a fraction of the dose that caused harm in animal testing. Phase I trials most often include healthy volunteers. However, there are some circumstances when clinical patients are used, such as patients who have terminal cancer or HIV and the treatment is likely to make healthy individuals ill. These studies are usually conducted in tightly controlled clinics called CPUs (Central Pharmacological Units), where participants receive 24-hour medical attention and oversight. In addition to the previously mentioned unhealthy individuals, “patients who have typically already tried and failed to improve on the existing standard therapies" may also participate in phase I trials. Volunteers are paid a variable inconvenience fee for their time spent in the volunteer center.

    Before beginning a phase I trial, the sponsor must submit an Investigational New Drug application to the FDA detailing the preliminary data on the drug gathered from cellular models and animal studies(...)

2021c

• (ClinicalTrials.gov, 2021) ⇒ https://clinicaltrials.gov/ct2/about-studies/glossary Retrieved 2022-01-11.
  • QUOTE: Phase 1: A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to determine the drug's most frequent and serious adverse events and, often, how the drug is broken down and excreted by the body. These trials usually involve a small number of participants.

2021d

• (Coursera, 2021) ⇒ "Design and Interpretation of Clinical Trials".
  • QUOTE: Phases I and II are often considered the learning phases of clinical trials, and phase III is considered the demonstration phase.

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