The MiniMox project aims to develop and qualify a paediatric formulation of moxidectin suitable for children from one to three years of age, to determine an appropriate dose of the formulation for this age range and to assemble data for submission to the US FDA in support of adding the paediatric formulation to the US FDA prescribing information.

AIM 1. Establish moxidectin’s paediatric formulation target product characteristics

The paediatric formulation target product characteristics are the prerequisite for initiation of pharmaceutical development (see AIM 3). They will be defined with up to three candidates selected for pharmaceutical development. This aim will be achieved through a review of potential paediatric formulation options taking into account the physicochemical characteristics of moxidectin, the manufacturability, and the acceptability.

AIM 2. ‘End-user’ feedback obtained on ‘End-user facing’ paediatric formulation target product characteristics

‘End-user facing’ formulation characteristics include taste, but also include posology and appearance – for example, options that include chewable forms, forms that can be mixed with soft foods or liquid formulations for swallowing should also be considered. To date, formulations that can be given to children as young as one year of age as a soft paste or mixed with soft foods have emerged as either acceptable or preferred, with liquids and gels considered least preferred. However, understanding of preferences of people in rural African areas is still limited and we will study this in onchocerciasis endemic areas in Cameroon. The outcome will complement the technical evaluation of formulation options (AIM 1) in the choice of formulations selected for pharmaceutical development (AIM 3).

AIM 3. Manufacture of selected formulations emerging from AIM 1 and AIM 2 with scale up of one formulation and release as Clinical Trial Material for AIM 4

Leading to this overall objective, MDGH will fund development of the manufacture of up to 3 candidate formulations likely to meet the target product characteristics at small batch scale. The formulation samples will permit assessment of the physicochemical characteristics of the moxidectin paediatric formulations, their manufacturability, and the suitability of current drug product release/stability assays for the new formulation(s). Based on this work, MDGH will scale the manufacture of one of these formulations to cGMP standards and conduct the testing required by cGMP for releasing Clinical Trial Material.

AIM 4. Determine the bioequivalence of the selected paediatric formulation with the approved 2 mg tablet formulation in a clinical study in Ghana

Bioavailability of the paediatric formulation and the FDA approved 2 mg tablet formulation will be quantified and bioequivalence will be demonstrated, providing input into AIM 5 and the data required for submission to the US FDA in support of addition of the paediatric formulation to the prescribing information (AIM 6). A bioequivalence clinical study, designed in compliance with best practice and regulatory guidance, will be performed in Ghana to evaluate the bioequivalence of the paediatric formulation to the FDA-approved 2 mg tablet. The design as reflected in the document ‘Essential Information on the clinical trial’ follows a typical bioequivalence model.

AIM 5. Enhancement of existing population pharmacokinetic model of moxidectin in children and adults and determination of paediatric dose

An enhancement of the moxidectin population pharmacokinetic model that has already been developed, which facilitates the evaluation of the impact of formulation changes, helps design future paediatric pharmacokinetic studies to minimise blood sampling and estimates an appropriate dose of the new paediatric formulation for 1 to 3 year old children. In addition to enhancing this model with the paediatric data from study MDGH-MOX-1006, MDGH will also utilise the data generated in the bioequivalence study to enhance their population pharmacokinetic model of moxidectin in children and adults.

AIM 6. Submission of supplemental New Drug Application to the US FDA in support of addition of the paediatric formulation to the US prescribing information

The paediatric formulation will be added to the US FDA moxidectin prescribing information. To achieve this, MDGH will prepare the submission once all data are available.

See “Work Packages” for further details on the clinical trials.