Impaired absorption of weakly basic drugs in patients with reduced gastric acidity can lead to loss of efficacy of the therapeutic agent. Hence, a robust formulation which can provide adequate exposure in achlorhydric patients is imperative to achieve the desired efficacy. In this report, formulation development of a weakly basic Merck compound A is described. Compound A shows lower solubility at higher pH and thus is prone to reduced exposure under conditions of achlorhydria, as the compound's solubility increases only in environments of less than pH 2. Several formulations with or without an acidifier were developed and characterized by in vitro dissolution and in gastric pH modified dog model to assess their bioperformance in high gastric pH conditions. To predict the bioperformance of these formulations in humans, a dissolution based absorption model was developed and validated against the observed PPI-interaction data in the clinic and the gastric pH-adjusted dog data. An additional absorption model was developed to allow for incorporation of the dog PK data to provide translation of preclinical to clinical exposure. Based on the in vitro dissolution, in silico absorption modeling and preclinical in vivo data, a citric acid-based formulation (F2) was selected for a human pharmacokinetic study. This study showed that exposures from F2 were not meaningfully different in the presence of proton pump inhibitor (PPI) as compared to non-PPI, thus confirming that the F2 formulation was successful in overcoming the achlorhydria effect. These efforts also highlighted that the complementary use of in vitro/in silico/in vivo (IVISIV) tools may be a helpful strategy in the development of formulations to overcome the achlorhydria effect and achieve adequate exposure in patients with high gastric pH.