Kiyohiko Nakai, Satofumi Iida, Hidenobu Aso, Masato Tobinai, Junko Hashimoto, and Takehiko Kawanishi
Chugai Pharmaceutical CO., LTD.
Objectives: M&S is a well recognized useful tool to simulate values related to certain endpoints for any clinical trials. Unfortunately, however, only limited numbers of reports are available up to now, where direct comparative analyses were conducted between the values simulated according to M&S and those actually obtained in patients. In the present study, therefore, in order to examine the validity of prospective M&S, we undertook direct comparisons between these two data sets on bone mineral density (BMD).
Methods: Modeling was performed based on both uCTx and BMD obtained in a Phase II clinical trial, where IBN was administered intravenously once a month for successive 6 months to Japanese patients with osteoporosis. The model[1] includes parameters of the dosage of IBN, uCTx and BMD was employed, and the linkage among each three parameters was analyzed. By employing this model, simulation was performed on BMD to be achievable in a Phase III clinical trial, in which IBN is to be successively administered for as long as 3 years. Finally, for the validation of the M&S, direct comparative analyses were conducted between the values simulated and those obtained in a Phase III clinical trial.
Results: At a dose level of 1 mg of IBN intravenously administered once a month, 50 percentile of the BMD changes from baseline simulated were 3.70，6.60, 7.66 and 7.91%, following 6, 12, 24 and 36 months, respectively. The median BMD changes actually observed, on the other hand, at each respective month of these treatments were found to be 4.46, 5.69, 6.87 and 8.01%. Thus, the simulated values and those actually observed well coincided with each other (the percent differences between them are below 20%).
Conclusions: The major findings that have been disclosed from the present study are the following three.
- The excellence of M&S for predicting the clinical effects of IBN against osteoporosis was verified.
- Beneficial clinical efficacies based on BMD following the treatments with IBN were found to be simulated in a quantitative manner by means of M&S.
- It can be envisaged that M&S is one of the powerful tools for significantly shortening development periods at least as far as the osteoporosis treatment is concerned.
References:
[1] Gieschke R et al. Modeling the Effects of Placebo and Calcium/Vitamin D Supplementation on the Course of Biomarkers of Bone Turnover in Osteoporotic Postmenopausal Women. 30th ESTC, 8-12 May 2003, Rome, Italy.
Reference: PAGE 22 (2013) Abstr 2700 [www.page-meeting.org/?abstract=2700]
Poster: Model evaluation