Clinical Trials Lecture Slides PDF

CLINICAL TRIALS Ma. Adeline G. Antonio, RPH, MS PHARM Facilitator, SLU-SNS Dept. Of Pharmacy 1st- Semester, AY 2020- 2021 Contents 1. IND product and 2. Phases of application Clinical Trials 3. Patent 4. Treatment IND  Instructions: 1. Read t...

CLINICAL TRIALS Ma. Adeline G. Antonio, RPH, MS PHARM Facilitator, SLU-SNS Dept. Of Pharmacy 1st- Semester, AY 2020- 2021 Contents 1. IND product and 2. Phases of application Clinical Trials 3. Patent 4. Treatment IND  Instructions: 1. Read through the slides. 2. Click on the links as instructed to further explore the topic /s. 3. Go to the Google Form to answer the assessment questions.  Investigational New Drug IND products are NEW drug vacccine or biological for FDA approval IND Application submitted by a sponsor or innovator company who wished to conduct a Terminologies clinical trial on an IND product Institutional Review Board (IRB) 5 experts and lay people who ensure the rights and welfare of human subjects Contents of the Investigational New Drug Application Click on the link to read on the preparation of the IND application https://www.researchgate.net/publication/287300821_The_Preparation_of_ a_Preclinical_Dossier_to_Support_an_Investigational_New_Drug_IND_App lication_and_First-in-Human_Clinical_Trial Meaning of NEW DRUG 1. New molecular entity (NME) 2. New active ingredient (new salt, new non-covalent derivative, new ester) 3. New dosage form NEW AI 4. New combination DF C 5. New formulation or new manufacturer F 6. New indication [no longer used] I 7. Drug already marketed without an approved NDA 8. OTC (over-the-counter) switch 9. New indication submitted as distinct NDA, consolidated with original NDA after approval 10. New indication submitted as distinct NDA - not consolidated POPULATION for Clinical Trials 20-80 healthy volunteers PHASE 1 100- 300 patients PHASE 2 300- +1000 patients PHASE 3   Use single sub-therapeutic doses given to 10 to 15 subjects  Yield initial pharmacological and pharmacokinetic data  Used to decide which of their drug candidates has the best Phase 0 pharmacokinetic parameters for humans. Human Microdose Studies  PHASE 1 20-80 PARTICIPANTS Objective Design 1. Assess the safety and 1. Single ascending design (SAD) studies by giving tolerability to the drug escalating single doses to small groups/cohorts until maximum tolerability is reached 2. Food effect studies 2. Mutiple Ascending dose (MAD) studies by giving escalating multiple doses to small groups /cohorts until maximum tolerability is reached SAD design MAD design By what mechanism does grapefruit juice increase or decrease drug plasma concentrations? Click the link to know about this interaction! https://www.youtube.com/watch?v=LhQ0wvJ4kJ0  PHASE 2 100- 300 participants Objective Design 1. Controlled design where different doses 1. Continue Phase 1 assessment arecompared to a pacebo (negative control) of efficacy and safety and active comparator drug (positive 2. Establish therapeutic doses control) 2. 12 – 16 weeks duration 3. Phase 2a to assess the dosing 3. Blinding techniques requirements while 2b focuses on drug efficacy Is it ethical to give a placebo to clinical trial participants? Click link to read on what a study found out. https://gcp.nidatraining.org/modules/6/pdf  PHASE 3 Objective Design 1. long- term safety data 1. Done under “daily clinical life” conditions meaning outpatient basis 2. drug’s overall benefit- risk relationship 2. Controlled design where different doses are compared to a pacebo (negative 3. Phase 3a aka Pivotal study data control) and active comparator drug collation to include in NDA application (positive control) 4. Phase 3b obtains additional safety 3. 6-12 months duration data, support publication, marketing 4. Double- blind cross- over study claims and prepares market launch  Do you think all clinical trial participants consent to the protocols? Click on the link to read on Informed Consent https://gcp.nidatraining.org/modules/6/pdf  PHASE 4 POST MARKETING SURVEILLANCE Objective Design 1. Pharmacovigilance 1. in real- world settings 2. Larger population 2. Assess effectiveness 3. Longer duration 4. Testing on certain new population 3. Assess cost- effectiveness ie. pregnant women 4. Meet regulatory requirements on changes in labeling, risk management/ minimization action plan  A patent is a right of the innovator company to enjoy a period of marketing exclusivity or monopoly to allow the company to recoup the cost of developing the drug product. Applicable also to extensions when there is change in color, shape or a PATENT new version, which will also require new clinical trials. Benefits A patent is an exclusive right that allows the inventor to exclude others from making, using, or selling the product of his invention during the life of the patent. Patent owners may also give permission to, or license, other parties to use their inventions on mutually agreed terms. Owners may also sell their invention rights to someone else, who then becomes the new owner of the patent.  The term of a patent shall be twenty (20) years from the filing date of the application. The patent must be maintained yearly, starting from the 5th year. Maintenance is by paying the annual fee upon the expiration of four (4) years from the Term of date the application was published. Payment of the annual fee may be made 3 months before the due date. Patent If the annual fee is not paid, the patent application shall be deemed withdrawn Eligibility or the patent shall be considered as lapsed from the day following the expiration of the period within which the annual fee was due. A grace period of six (6) months shall be granted for the payment of the annual fee, upon payment of the prescribed surcharge for delayed payment.  What are the pharmacologic categories of the 3 products with the highest sales? 56 DRUGS PATENTS EXPIRING IN 2020- 2022 What happens when a drug Click on the link to help you answer the patent expires? questions provided here. https://www.greyb.com/drug-patents- expiring-2020-2021-2022/ Do these mean the same thing???  TREATMENT INVESTIGATIONAL NEW DRUGS Made available to desperately ill patients as early in the development stage as possible (Phase III) , IF : 1. Evidence of efficacy and safety are present 2. No comparable alternate drug is available 3. Patients are not eligible to be in a definitive clinical trial due to their condition  ORPHAN DRUGS These are drugs that prevent, diagnose or treat rare diseases; where manufacturers are granted a 7-year exclusive marketing for the product. A rare disease is defined as a disease/condition that affects