Regulatory Open Forum

I would like to conduct a clinical study of an approved drug, co-administered with additional free excipient, for the approved indication/patient population. Although the excipient is already present in the approved formula, in this application it will also be co-administered as an additive with the intent of improving bioavailability.

Co-administration will not result in higher API exposure, therefore we do not anticipate that additional safety data will be required for exposure to the API at the approved dose level. Regarding the excipient: because it is already present in the approved formula, and is a common excipient used in many other pharmaceuticals, safety data providing an adequate exposure margin for the higher dose level may already be publicly available. Could this safety data be referenced to circumvent the need for a stand-alone toxicology study of the excipient at the higher dose level?

In terms of the clinical trial design: our thought is to study the novel therapy of approved drug+free excipient vs the approved drug alone as a comparator in a Phase 2/3 type study. The study would be designed to demonstrate whether bioavailability in the co-administration arm is superior to the approved drug only arm as a primary endpoint; the original 'approval' endpoints for the indication could be secondary or co-primary endpoints. Would it be appropriate to propose moving directly into a Phase 2/3 study such as this, given the circumstances? And how would the approved drug be sourced for the study, if the study is not sponsored by the company that licensed it originally?

Thank you for your help.

I would like to conduct a clinical study of an approved drug, co-administered with additional free excipient, for the approved indication/patient population. Although the excipient is already present in the approved formula, in this application it will also be co-administered as an additive with the intent of improving bioavailability.

Co-administration will not result in higher API exposure, therefore we do not anticipate that additional safety data will be required for exposure to the API at the approved dose level. Regarding the excipient: because it is already present in the approved formula, and is a common excipient used in many other pharmaceuticals, safety data providing an adequate exposure margin for the higher dose level may already be publicly available. Could this safety data be referenced to circumvent the need for a stand-alone toxicology study of the excipient at the higher dose level?

In terms of the clinical trial design: our thought is to study the novel therapy of approved drug+free excipient vs the approved drug alone as a comparator in a Phase 2/3 type study. The study would be designed to demonstrate whether bioavailability in the co-administration arm is superior to the approved drug only arm as a primary endpoint; the original 'approval' endpoints for the indication could be secondary or co-primary endpoints. Would it be appropriate to propose moving directly into a Phase 2/3 study such as this, given the circumstances? And how would the approved drug be sourced for the study, if the study is not sponsored by the company that licensed it originally?

Thank you for your help.

I would like to conduct a clinical study of an approved drug, co-administered with additional free excipient, for the approved indication/patient population. Although the excipient is already present in the approved formula, in this application it will also be co-administered as an additive with the intent of improving bioavailability.

Co-administration will not result in higher API exposure, therefore we do not anticipate that additional safety data will be required for exposure to the API at the approved dose level. Regarding the excipient: because it is already present in the approved formula, and is a common excipient used in many other pharmaceuticals, safety data providing an adequate exposure margin for the higher dose level may already be publicly available. Could this safety data be referenced to circumvent the need for a stand-alone toxicology study of the excipient at the higher dose level?

In terms of the clinical trial design: our thought is to study the novel therapy of approved drug+free excipient vs the approved drug alone as a comparator in a Phase 2/3 type study. The study would be designed to demonstrate whether bioavailability in the co-administration arm is superior to the approved drug only arm as a primary endpoint; the original 'approval' endpoints for the indication could be secondary or co-primary endpoints. Would it be appropriate to propose moving directly into a Phase 2/3 study such as this, given the circumstances? And how would the approved drug be sourced for the study, if the study is not sponsored by the company that licensed it originally?

Thank you for your help.