Table 1.

Methodological overview of DIALOGUEs 1, 2, and 4

Study CharacteristicsDIALOGUE 1DIALOGUE 2DIALOGUE 4
Clinicaltrials.gov identifier: NCT02021370aClinicaltrials.gov identifier: NCT02021409aClinicaltrials.gov identifier: NCT01975818b
RegionEurope and the Asia-PacificEurope and the Asia-PacificUnited States and Japan
DesignRandomized, double-blind, placebo-controlled, fixed-dose trialOpen-label, active comparator-controlled, variable-dose trial; comparator: darbepoetin alfaOpen-label, active comparator-controlled, variable-dose trial; comparator: epoetin alfa or beta
Patient populationMen and women (aged ≥18 yr) with a diagnosis of anemia of CKD
Main inclusion criteriaESA-naïve eGFRc <60 ml/min per 1.73 m2 but not on dialysis; mean Hb <10.5 g/dldOn stable dose of darbepoetin alfa eGFRc <60 ml/min per 1.73 m2 but not on dialysis; mean Hb 9.0–12.0 g/dleOn stable dose of epoetin alfa/beta; on dialysis; mean Hb 9.0–11.5 g/dlf
TreatmentFixed doses of molidustat (25, 50, or 75 mg once daily; 25 or 50 mg twice daily) or placebo (1:1:1:1:1:1 randomization)Molidustat (starting doses 25, 50, or 75 mg once daily) and plus optional 15, 100, and 150 mg or continued darbepoetin treatment (1:1:1:1 randomization)Molidustat (starting doses 25, 50, 75, or 150 mgg and plus optional 15, 100, 200 mg once daily) or continued epoetin treatment (final allocation, 1:1:1:0.6:1)
Primary end pointMean change in Hb level between baseline and the last 4 wk of treatment
Key secondary end pointshChange in Hb during first 12 wk of treatment; rate of change of Hb over timeResponse to treatmenti; time in target rangei; proportion of patients with Hb levels above and below target rangei
  • DIALOGUE, DaIly orAL treatment increasing endOGenoUs Erythropoietin; ESA, erythropoiesis-stimulating agents; Hb, hemoglobin.

  • a Registered December 2013.

  • b Registered October 2013.

  • c Defined according to the Modification of Diet in Renal Disease (31) or the formula devised by Matsuo et al. (32).

  • d Mean of all local laboratory Hb measurements (at least two measurements must be taken ≥2 days apart) during the 4-week screening period, with the last screening Hb measurement within 10 days before randomization, all measurements come from the same local laboratory for any given subject, and the difference between the lowest value and the highest value is ≤1.2 g/dl.

  • e Mean of all local laboratory Hb measurements (at least two measurements must be taken ≥2 days apart) during the 4-week screening period, none of the measurements can be <9.0 or >12.0 g/dl, none of the measurements can be <9.0 g/dl, all measurements must come from the same local laboratory for any given subject, and the difference between the lowest level and the highest level is ≤1.2 g/dl.

  • f Mean of all local laboratory Hb measurements (at least two measurements must be taken ≥2 days apart) during the 4-week screening period, none of the measurements can be <9.0 or >12.0 g/dl, all measurements come from the same local laboratory for any given subject, and the difference between the lowest level and the highest level is ≤1.2 g/dl.

  • g Added after a protocol amendment.

  • h For a full list of secondary end points, see Supplemental Table 2.

  • i Definitions of response and target range vary between DIALOGUE 2 and DIALOGUE 4; see Supplemental Table 2 for further information.