Since 1999, the Hawaii Clinical Research Center has collaborated with sponsors in planning and conducting inpatient and outpatient studies for the purpose of generating data supportive of submissions elsewhere, primarily bridging trials for Japan. While Japan has some difficulty in conducting the necessary studies to justify new compound approvals, HCRC is pleased to do what it can to assist with this process.

Japanese residents of Hawaii and whose parents or grandparents born in Japan, are eager to participate in studies which support the introduction of contemporary medications to our sister country. They have been very willing to stay for up to two weeks within our 30-bed Hale Ekahi residential Phase I unit, or come regularly to our outpatient clinic for study visits. Recruitment is especially efficient and rapid. Study conduct, which might involve an array of specialty physicians, investigations, procedures, and resources, is a welcome challenge.

The several Japan bridging studies we have conducted so far have proceeded exceptionally well. Some of the summaries of these studies follow:

• An outpatient, open-label pharmacokinetic study of study drug following oral or topical administration in healthy middle-aged and elderly Japanese and Caucasian subjects matched by age and gender. Successfully recruited 40 Japanese and 40 Caucasian subjects within a four-week period. (January 2000)

• A seven-day, outpatient, open-label, randomized, parallel group, multiple-dose pharmacokinetic study following administration of study drug in normal, healthy male Japanese subjects. Successfully recruited 15 Japanese and 15 Caucasian subjects within a two-week period. (May 2000)

• A six-day, outpatient, single-dose, crossover comfort evaluation of study medication and comparator medication in normal, healthy Japanese subjects. Successfully recruited 19 Japanese male and 19 female subjects within a one-week period. (September 2000)

• An eight-day, outpatient, double-masked, randomized, parallel, safety study of study medication and comparator in normal, healthy male Japanese Subjects. Successfully recruited 60 Japanese subjects in three weeks. (November 2000)

• A seven-day, residential, open-label, safety study of study medication in normal, healthy male Japanese subjects. Successfully recruited 10 Japanese subjects in one week to stay at the Hale Ekahi residential unit. (April 2001)

• A nine-day, residential, double-masked, randomized multiple-dose pharmacokinetic study following administration of study medication in normal, healthy, male Japanese and Caucasian subjects. Successfully recruited 15 Japanese and 14 Caucasian subjects in three weeks to stay at the Hale Ekahi residential unit. (June 2001)

• A fifteen-day, residential, double-masked, randomized, multiple-dose, safety/pharmacokinetics study following administration of study medication in normal, healthy, male Japanese and Caucasian subjects. Successfully recruited 12 Japanese and 12 Caucasian subjects in three weeks to stay at the Hale Ekahi residential unit. (September 2001)

• A fifteen-day, residential, double-masked, randomized, multiple-dose, safety/pharmacokinetics study of study medication following administration in normal, healthy, male Japanese subjects. Successfully recruited 12 subjects in one week to stay at the Hale Ekahi residential unit. (November 2002)

• A one-month out-patient, open-label, multi-center study to assess blood concentrations, tolerability and efficacy of study drug in Japanese infants and children with Atopic dermatitis. Successfully recruited 10 Japanese infants and children aged 3 months to 12 years in two months. (November 2002)

• A residential and outpatient, double-blind, parallel group, placebo-controlled comparing pharmacokinetics, pharmacodynamics, safety and tolerability between healthy Caucasian and Japanese volunteers after single and multiple doses of study medication. Successfully recruited 40 Japanese and 40 Caucasian subjects in two months to stay at the Hale Ekahi residential unit. (April 2003)