Dose Ranging & MTD Studies
Dose Range-Finding Studies for Your Candidate
Dose range-finding or maximum tolerated dose (MTD) studies are the first stage of toxicology assessments that help developers identify the appropriate dose for later regulatory studies, including single and repeat dose toxicity. They also help you understand key aspects of your compound to inform GLP studies and ensure a successful IND filing.
WuXi AppTec is an experienced partner in general toxicology testing and can help you build an in vitro ADME program that includes the right dose ranging assays and associated data for successful regulatory submission.
Expert Dose Ranging & Toxicity Studies
As an end-to-end toxicology testing partner, we offer the full suite of dose studies tailored to your compound needs. Beyond dose range-finding, this includes single dose acute toxicity testing and repeat-dose chronic toxicity studies for
Dose Range Finding
Dose ranging studies help you identify proper dosage to inform later stage GLP studies.
Single Dose Acute Toxicity
Acute toxicity testing helps you identify potential adverse effects of new drug candidates.
Repeat Dose Toxicity
Chronic toxicity testing helps you evaluate the effects of repeat administration over a defined period of time.
Dose Range-Finding in Drug Development
Our dose ranging studies provide the proper data you need to inform later-stage clinical trials. Here’s an overview of which data you can expect to receive.
Example Chart
Dose range finding is a critical part of the drug development lifecycle, playing important roles through the discovery, preclinical to IND, and clinical stages.
Dose Ranging Studies FAQ
What are dose ranging studies?
Non-GLP dose range-finding (DRF) studies help drug developers select the appropriate doses for later pivotal regulatory studies.
By administering varying dose levels to different species and closely monitoring for adverse effects, drug developers can identify a range of dose levels for GLP pivotal studies. The high dose level selected is usually the maximum tolerated dose; low and middle doses are often successive half-log intervals of the high dose. For example, if your high dose is 100 mg/kg, low and mid doses are 10 and 30 mg/kg, respectively. DRF studies are needed to help determine your maximum tolerated dose.
Why are dose ranging & MTD studies necessary?
Dose range-finding studies are an essential precursor to pivotal studies:
- Single dose acute toxicity studies identify potential adverse effects of the new drug candidate.
- Repeat dose chronic toxicity studies evaluate the effects of repeat administration over a defined period of time.
Unless your clinical plan is only a single dose, your pivotal, or IND-enabling, study will more often than not be a repeat dose study for 14-28 days. This study is critical to your IND approval and requires a robust protocol, an experienced laboratory that will generate and interpret quality data, and GLP compliance. Because of the rigorous standards for GLP pivotal studies it’s important to have the best data available informing your study design before you initiate the GLP study. Dose range-finding studies are how you get there.
What can dose ranging studies tell me about my drug compound?
Dose range-finding studies help you learn a lot about your drug beyond just dose level.
For example, when you take blood samples to look at the pharmacokinetics (PK) of the drug in the animals, you can correlate signs of toxicity to the drug levels and kinetics and better design the timing of in-life parameters in your GLP study.
Look for signs of toxic effects using the following parameters:
- Body weights
- Clinical observations
- Hematology
- Clinical chemistry
- Coagulation parameters
- Necropsy
- Neurological observations (for neurological drugs)
- Cytokines (for immune-stimulating drugs)
- Flow cytometry (for immunomodulatory drugs)
Ultimately, dose range-finding studies present an excellent opportunity to learn more about your drug so you’re ready for GLP and IND filing. Use this as a chance to get the most information as possible so you can create a robust GLP study.
Are dose ranging studies cost-effective?
Toxicology studies that result in too much toxicity or none at all are not ideal. If your doses are too high, you may not have a NOAEL (No Observable Adverse Effect Level) that is used to calculate your starting dose on the clinic. If you have no toxic effects at all, and can demonstrate sufficient exposure, you may have to use a maximum feasible dose approach to assign a high dose (see again ICH M3R2 Figure 1). Dose range-finding studies can be repeated until you find the appropriate dose and route of administration. This is much more cost effective than repeating a GLP study.
How do dose ranging studies add value to my testing program?
Non-GLP dose range-finding (DRF) studies help drug developers select the appropriate doses for later pivotal regulatory studies.
What is the turnaround time for dose ranging studies?
14-28 Days
What kind of data do I get from dose ranging studies?
Dose range-finding studies help you learn a lot about your drug beyond just dose level. For example, when you take blood samples to look at the pharmacokinetics (PK) of the drug in the animals, you can correlate signs of toxicity to the drug levels and kinetics and better design the timing of in-life parameters in your GLP study.