The abuse of prescription drugs, such as opioids, stimulants, and central nervous system (CNS) depressants has become a prominent public health concern in the United States and around the world. Due to the increasing rate of prescription drug abuse, regulatory requirements for the abuse potential assessment of CNS-active drugs have become increasingly stringent, particularly in the US (i.e., FDA). The process by which new molecular entities (NMEs) are evaluated by sponsors and reviewed by regulators has evolved over time, with many biopharmaceutical companies now being required to conduct a human abuse potential/human abuse liability (HAP/HAL) study.

Human abuse potential studies are typically conducted as single-dose, double-blind, randomized, placebo and active-controlled, crossover studies that evaluate the subjective effects of the investigational drug in “recreational” (non-dependent) drug users. The comparison with placebo is used to make conclusions about ‘absolute’ abuse potential (i.e., determining whether the drug has any intrinsic abuse potential). The comparison with the active comparator, a scheduled drug with known abuse liability, is used to make conclusions about ‘relative’ abuse potential. The data from HAP studies is important towards developing abuse-related drug product labeling and in determining whether a NME will be scheduled under the DEA’s Controlled Substances Act.

Over the last 20 years, the team at Dr. Vince Clinical Research has developed deep experience in the design, planning, and conduct of HAP studies, taking into consideration the unique subject population, critical endpoints, and operational complexities which are crucial towards successful study execution.

In order to conduct Human Abuse Potential studies, comprehensive pharmacy capabilities are required. DVCR’s pharmacy team has over 50 years’ experience in clinical pharmacology studies, including extensive expertise with the handling and manipulation of study drugs for various routes of administration in HAP/HAL clinical trials. These include, but are not limited to injectable formulations (e.g., IV, IM), nasal insufflation, and powder in capsule (PIC).

For those studies requiring blinding of the reference therapy, our team utilizes over-encapsulation as an effective strategy in maintaining the blind. Not only does our team have the ability to provide accurate individual doses for trial volunteers, but our state-of-the-art cGMP pharmacy includes a USP-795 compliant non-sterile compounding room. This room features independent narrow spectrum 570nm amber LED lights for handling photosensitive API study drug. In addition, any API powder requiring weighing for batch preparation will be performed using our analytical balance. The balance is housed within a Type B PowderSafe™ enclosure outfitted with a HEPA filter and resides on an anti-vibration table to improve balance performance.

Volunteer Recruitment and Retention for HAL Studies

Targeted volunteer recruitment is a critical element in the success of Human Abuse Liability studies. HAP studies are to be conducted in experienced drug users who have experience using drugs which are in the same pharmacological class as the investigational product. The use of drug-naïve subjects has not been validated scientifically as being able to provide accurate information on the abuse potential of a drug.

Therefore, having a robust database of potential study volunteers that have experience abusing the drug class and are able to meaningfully discriminate between the selected positive control and the placebo is essential in the successful operational conduct of these complex clinical trials. Furthermore, it is imperative that Sponsors plan accordingly to account for potential volunteer dropouts in order to ensure that the study is adequately powered.

DVCR maintains an active database of substance users that have experience abusing various drug classes. The 2017 FDA Guidance Assessment of Abuse Potential of Drugs notes that “Sponsors should include a fair representation of races and sexes as participants in clinical trials so that clinically significant differences in response can be detected. The FDA Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs (1993) should be followed (2).” DVCR is committed to both speed and diversity in recruitment and facilitates these goals with luxurious amenities for trial volunteers to enjoy