C-QT Analysis May Eliminate the Need for a TQT Study
PK/PD Analysis can sometimes eliminate the need for a Thorough QT/QTc (TQT) study. Using an ICH E14 accepted approach called Concentration-QT (C-QT) Analysis, Nuventra can help establish the risk of prolonging the QT interval and possibly avoid a TQT study completely. A C-QT Analysis is a low-cost and efficient service compared to running a TQT study.
Our team takes PK and 12-lead ECG data that has already been collected, or that will be collected, from standard clinical studies conducted during drug development and performs a C-QT analysis using PK/PD modeling techniques (exposure-response). If valid data are available from therapeutic and supra-therapeutic doses, then you can apply for a TQT waiver.
In other cases, a TQT study may or may not be required depending on how much information is available at supra-therapeutic doses, expectations from drug interactions, how the QT data were collected (e.g., triplicate vs single readings, manual vs computerized readings), and whether or not there is an effect of the drug on the heart rate.
If a TQT study is still required after a C-QT analysis has been completed, there is still value added because the C-QT analysis contributes to the more efficient design of a TQT study.
Nuventra matches up the PK Data and the ECG Data collected in standard clinical studies such as any combination of first time in human (FTIH), single ascending does, multiple ascending does, and proof of concept phase 2. These standard clinical studies have to be conducted regardless, but the TQT study does not. We use industry-standard software (NONMEM) and apply proven techniques that have been used to support the approval of drugs on the market. The key is to design the studies that are already planned in a way that ensures they will obtain the best data for a Concentration-QT Analysis (e.g., wide dose range, matching PK and ECG collection times, triplicate ECG readings, etc.).
Concentration-QT Analyses are only as good as the data collected during clinical development. Nuventra strongly recommends engaging clients prior to executing any studies that will support a Concentration-QT Analysis. However, we have experience conducting Concentration-QT Analysis on legacy studies as well.
- A TQT study can cost upwards of $5 million to conduct, interpret and report. The study may take over a year to complete.
- The FDA-accepted PK/PD technique, C-QT Analysis, costs $150,000 to $300,000 to assess QT/QTc prolongation.
- C-QT may result in a greater than ten fold cost saving and can be completed in just a quarter of the time compared to conducting a thorough QT/QTc study.
- Concentration-QT Analysis uses standard PK/PD modeling and simulation techniques (called exposure-response or E-R). These E-R techniques: 1) Are used in most drug development programs 2) Are readily accepted by the FDA and 3) Have supported the approval of drugs currently on the market.
|Parameter||Thorough QT/QTc (TQT) Study||Concentration-QT analysis|
|Cost||$3,000,000 to $5,000,000||$150,000 to $300,000|
|New clinical study||Yes. 40 to 60 subjects in TQT study.||No. Use existing data.|
|De-risk drug program to cardiac liability||Yes||Yes|
|Avoid clinical study||No||Yes|