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In this paper, we consider the capacitated multi-item lot sizing problem with setup times. The problem is to schedule J different items over a horizon of T periods with the objective to minimize the sum of setup cost and inventory holding cost. To achieve feasible high-quality solutions, we propose a new solution approach which hybrids Nested Partitions and Mathematical Programming (HNP-MP). Nested Partitions is a partitioning and sampling based heuristic method with a global perspective on the problem. In the proposed new method the Mathematical Programming method is implemented to calculate the promising index and to provide a good guidance on partitioning in the Nested Partitions framework. A time-oriented decomposition heuristic method, Relax-and-Fix, is also implemented to obtain good promising regions and speed up the computational process. Computational results based on benchmark test problems show that the approach is computationally tractable and is able to obtain good results. The approach outperforms other state-of-the-art approaches found in the literature.