Lecture 8: Drug Development II

Flashcards covering the drug development process, historical regulatory milestones, and clinical trial phases based on the lecture by Johannes Stanta.

When did Johannes Stanta participate in a Phase 1 study for Fingolimod (Novartis)?

In $2009$

According to William Witherings in $1789$, what are useful medicines in too large doses?

Useful medicines in too large doses are poisonous.

What toxic substance was contained in Elixir Sulfanilamide in $1937$, resulting in $107$ deaths?

Diethylene Glycol

What legislation was passed by Congress one year after the Elixir Sulfanilamide disaster?

The Federal Food, Drug and Cosmetic Act

Why did Sulfathiazole Tablets cause $300$ deaths in $1941$?

They were tainted with the sedative Phenobarbital.

What was the brand name of the sleeping tablet launched by Chemie Grünenthal in $1957$ that caused the Thalidomide disaster?

Contergan

How many babies were estimated to have birth defects caused by Thalidomide?

$10,000$ to $20,000$ babies

List four Contract Research Organisations (CROs) mentioned in the lecture notes.

ACM Global Lab, Charles River, LabCorp, and PPD (also Quotient).

What are the three categories of drug targets identified during basic research?

Receptors, Enzymes, and Transport proteins.

What standard of practice is required for Preclinical Development versus Clinical Development?

Preclinical Development requires GLP (Good Laboratory Practice), while Clinical Development requires GCP (Good Clinical Practice).

In animal toxicology, what do the '3R' principles stand for?

Reduce, refine, replace

What are the default rodent and non-rodent species used in animal toxicology?

The default rodent is the rat and the default non-rodent is the beagle.

What are the three dose groups used in small molecule animal toxicology studies?

Low (no toxicology), intermediate, and High (toxicology expected in target organ).

Which parameters are checked during the Clinical Pathology phase of toxicology?

Haematology/clinical chemistry, Kidney and liver function, and Coagulation.

What are the core battery studies in Safety Pharmacology?

CNS (Central Nervous System), Respiratory, and Cardiovascular.

In Safety Pharmacology, which specific cardiovascular assay measures repolarization concerns?

The hERG (kr) assay

What is the primary question addressed during Phase I of a clinical trial?

Is it safe?

How long is the typical timeline for a Phase I clinical trial process?

A $6$ month process

In the $2016$ BIA 10-2474 trial, how much higher was the dose given compared to the calculated receptor occupancy requirement?

They did $400 \times$ the dose needed.

What are the two main objectives of Phase II clinical trials (Proof of Concept)?

How much should be given to be effective, and how well does the treatment work?

How many patients are typically involved in a Phase III clinical trial?

$1000+$ patients

What is the focus of Phase IV clinical trials?

Post marketing surveillance to detect rare or long-term adverse effects.

Why was the appetite suppressant Sibutramine withdrawn from the market in $2010$?

Due to heart attack and stroke risks.

What adverse effects led to the withdrawal of the anti-obesity drug Rimonabant in $2008$?

Severe depression and suicide

Why was the narcotic painkiller Hydromorphone withdrawn in July $2005$?

High risk of accidental overdose with alcohol.