Phase 0 1 2 3 Also known as Microdosing Human Pharmacology Therapeutic Exploratory 2a 2b Therapeutic Confirmatory 3a 3b Objective PK /PD /Other Enable go/no-go decisions to be based on relevant human models instead of relying on sometimes inconsistent animal data. Safety & tolerability-M aximum tolerated dose PK PD safe dose range PK Safety Efficacy PK Safety Efficacy Safety Special studies (Qol, DDI, FDI) Sub group Efficacy Safety Special studies (Qol, DDI, FDI, PE) Info for mkt Subjects Generally Healthy volunteer Generally Healthy volunteer Patients (homogenous).
Patients (heterogeneous) Patients (heterogeneous) Patients (heterogeneous) Site Single, CPU Generally Single, CPU Generally Single, Specialized hospital units Generally Multiple, Specialized hospital units Generally Multiple, Multispecialty Hospital Generally Multiple, Multispecialty Hospital Outcome PK/PD/Other Accelerator mass spectrometry (AMS) Safe dose range Bioavailability Nature of adverse drug reactions Safe dose schedule, characterization of dose response curve, Nature of adverse drug reactions Efficacy, Nature of adverse drug reactions Confirm efficacy.
Information for regulatory submission Confirm efficacy Information for Mkt Secondary: drug activity, potential therapeutic benefits Comparison with standard Comparison with competitor Prerequisites Preclinical data + EC & RA approval Preclinical data + EC & RA approval Preclinical data + Clinical+ EC & RA approval Preclinical data + Clinical+ EC & RA approval Preclinical data + Clinical+ EC & RA approval Preclinical data + Clinical+ EC & RA approval Control Generally no control Placebo or Generally no control Placebo or active Generally active Generally active.
Types – SAD & MAD Pilot & Pivotal Mandatory & optional The description of the study population should be stated in the inclusion & exclusion criteria, wherein care should be taken to identify the characteristics of the subject which impacts the endpoint. Therefore disease, concurrent illnesses and medication and other patient related confounding factors including hypersensitivity should be taken into consideration while specifying the criteria. This should include disease characteristics, demographic characteristics, and baseline values of any clinically relevant variables.
Sample I/E criteria Inclusion Criteria – A subject will be eligible only if all of the following criteria apply: a. Males or females between the ages of 18 and 50. b. No clinically important abnormal physical findings at the screening examination. c. Normal or clinically acceptable ECG. d. Normal blood pressure (systolic: 90-140 mmHg; diastolic: 50-90 mmHg) and heart rate (40-100 bpm). e. Body Mass Index of 19. 0-29. 0 (kg/m2). f.
Ability to communicate well with the investigator and to comply with the requirements of the entire study.g. Willingness to give written informed consent (prior to any study-related procedures being performed) and to be able to adhere to the study restrictions and examination schedule. Exclusion Criteria- A subject will not be eligible if any of the following criteria apply: a. Administration of any investigational drug in the period 0 to 45 days before entry to the study. b. Use of any prescription medication during the period 0 to 30 days or over-the-counter medication during the 0 to 5 days before entry to the study. c.
Donation or loss of greater than 400 ml of blood in the period 0 to 12 weeks before entry to the study. d. Serious adverse reaction or hypersensitivity to any drug. e. Inability to communicate or co-operate with the investigator because of a language problem, poor mental development or impaired cerebral function. f. History of drug dependence (except tobacco) or psychiatric illness within the past 2 years. g. Consumption of alcohol within 24 hours prior to dose administration. h. Females who are lactating or at risk of pregnancy i.
Females with a positive serum pregnancy test at screening or positive urine pregnancy test on admission to study site. j. Presence of pain incurred by unknown causes. k. History of asthma or other respiratory disease. l. History of neurologic or neuromuscular disease. m. History of hypotension or cardiovascular disease. n. History of bladder or urethral disease. o. Inability to refrain from smoking during study days. p. Any other condition which, in the opinion of the investigators, is likely to interfere with the successful collection of the measures required for the study.