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A clinical pharmacology trial, which examines the safety and pharmacodynamics of an investigational drug, is typically the first time that the drug is administered to humans. We are, therefore, often forced to maintain some restrictions on the trial conditions; for example, incremental doses in succeeding stages may be necessary when safety is concerned, and the repetition of the treatment on the same subject may be restricted in terms of the imposition on and convenience of subjects. The present paper investigated optimal trial designs under such restrictions, adopting Ds-optimality (D-optimality for subset) as the criterion. In order to identify the optimal design, all admissible designs that satisfy the restrictions were listed in a lexical order and their optimality was compared. As a result, it was revealed that a relatively high number of subjects were allocated lower doses in the optimal design when the increment restriction was regarded as relevant, whereas more reasonable designs were identified as optimal when the restrictions were modified.