B035: Qualifying for pediatric exclusivity–challenges in study design

• Published in: American journal of hypertension 2000-04, Vol.13 (S2), p.66A-67A
• Main Authors: Burriss, S.W., Cargo, P.H., Humphrey, D.M., Rolf, C.N., Gillen, M.V., O'Kelly, R.L.
• Format: Article
• Language: English
• Subjects: exclusivity; hypertension; Pediatric; trial design
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(00)00824-4

The 1997 Food and Drug Administration Modernization Act (FDAMA) requires FDA to develop, prioritize, and publish a list of approved drugs for which additional pediatric information may produce health benefits in the pediatric population. Under this regulation, NDA holders may obtain 6 months additional product exclusivity in exchange for conducting FDA approved pediatric research. In June 1998, Wyeth-Ayerst and Procter & Gamble Pharmaceuticals began developing a pediatric clinical study program to satisfy these requirements and to address any potential safety and ethical concerns. The FDA Written Request outlined four possible trial designs for dose ranging information, safety data and pharmacokinetics (PK) data in four specific pediatric age groups. Three protocols were developed to address the FDA Written Request: two PK studies (children aged 0–6 years and children aged 6–15 years) and a safety and efficacy study (diagrammed below) Figure 1:Figure 1.*Doses of Bisop/HCTZ were escalated as needed to achieve BP control (defined as a sitting SBP and/or DBP ≤90th percentile for age, sex and height). The HCTZ arm of the study provided an active control to further establish the bisoprolol dose response. 145 patients were screened by a total of 23 investigators. 110 patients were randomized; 9 patients were dropped after randomization. Recruitment activities included: investigator chart review, referrals from primary care physicians, BP screening at local schools and community advertising. The submission was completed March 6, 2000.