This is a single-center, randomized, cross-over placebo controlled study to evaluate the changes in tear volume by P-321 Ophthalmic Solution and Placebo. The study will enroll subjects with tear deficient dry eye disease to receive sequentially one of two treatment sequences: P-321 Ophthalmic Solution then Placebo or Placebo then P-321. The study will consist of two Phases: In each Phase, subjects will be treated with P-321 Ophthalmic Solution under the same study design.