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. 2020 Apr 27;5(6):801-812.
doi: 10.1016/j.ekir.2020.03.011. eCollection 2020 Jun.

The NOCTURNE Randomized Trial Comparing 2 Tolvaptan Formulations

Ronald D Perrone  1 , Arlene B Chapman  2 , Dorothee Oberdhan  3 , Frank S Czerwiec  4 , Olga Sergeyeva  5 , John Ouyang  6 , Susan E Shoaf  7
Affiliations

The NOCTURNE Randomized Trial Comparing 2 Tolvaptan Formulations

Ronald D Perrone et al. Kidney Int Rep. .

Erratum in

Abstract

Introduction: Tolvaptan, a treatment for autosomal dominant polycystic kidney disease (ADPKD), inhibits vasopressin V2 receptor signaling, which causes aquaretic adverse events (AAEs). The short-term efficacy and tolerability of a once-daily, modified-release (MR) formulation was assessed relative to the twice-daily, immediate-release (IR) formulation.

Methods: This Phase 2 multicenter, randomized (1:1:1:1), placebo-controlled, double-blind, placebo-masked, parallel-group study (NCT01451827) compared tolvaptan MR 50 mg once daily or tolvaptan MR 80 mg once daily with tolvaptan IR 60/30 mg daily split dose and placebo over 8 weeks in 177 subjects. The primary endpoint was percent change from baseline in total kidney volume (TKV) at week 3. Other endpoints included tolerability, assessed by adverse events and quality of life (QOL) measures.

Results: Mean percentage decreases in TKV at week 3 were observed for the pooled group of all (MR+IR) tolvaptan-treated subjects (-2.07%), tolvaptan MR 80 mg (-2.55%), and tolvaptan MR 50 mg (-2.46%) versus placebo (0.09%; P < 0.02 for each comparison with placebo), whereas the decrease with tolvaptan IR 60/30 mg (-1.17%; P = 0.24) did not reach significance. All tolvaptan regimens were associated with AAEs, but scores on ADPKD-specific and generic patient-reported outcome assessments showed little impact based on dosage on overall health-related QOL versus placebo.

Conclusion: Tolvaptan MR and tolvaptan IR demonstrated similar short-term efficacy, tolerability, and safety, with low impact on multiple measures of QOL. Conclusions regarding long-term efficacy are limited by the short duration of follow-up.

Keywords: autosomal dominant polycystic kidney disease; clinical trial; pharmacodynamics; pharmacotherapy; tolvaptan.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Study design. R, immediate release; MR, modified release.
Figure 2
Figure 2
Percent change from baseline in total kidney volume at week 3 (primary endpoint) and week 8. Intent-to-treat population, observed cases. ∗P < 0.05. P values are for comparisons of tolvaptan week 3 versus placebo week 3 and tolvaptan week 8 versus placebo week 8. IR, immediate release; MR, modified release; TKV, total kidney volume.
Figure 3
Figure 3
Number of (a) daytime and (b) nighttime urine voids. ∗P < 0.05 versus placebo. IR, immediate release; MR, modified release.
Figure 4
Figure 4
Twenty-four-hour urine volume. ∗P < 0.0001 versus placebo. IR, immediate release; MR, modified release.
Figure 5
Figure 5
(a) Urinary Frequency, (b) Urinary Urgency, and (c) Nocturia domain scores on the Autosomal Dominant Polycystic Kidney Disease Urinary Impact Scale. Increases in score from baseline were significantly (P < 0.001) greater for each tolvaptan group versus placebo. IR, immediate release; MR, modified release.
Figure 6
Figure 6
Subjects with spot urine osmolality <300 mOsm/kg at trough, week 3, and week 8. P values for comparison versus placebo. ∗P < 0.01; †P < 0.0001. IR, immediate release; MR, modified release.
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Comment in

  • No Change in Nocturia After NOCTURNE.
    Meijer E, Heida JE, Gansevoort RT. Meijer E, et al. Kidney Int Rep. 2020 Apr 28;5(6):762-765. doi: 10.1016/j.ekir.2020.04.014. eCollection 2020 Jun. Kidney Int Rep. 2020. PMID: 32519995 Free PMC article. No abstract available.

References

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    1. Perrone R.D., Chapman A.B., Oberdhan D. A randomized trial of modified-release versus immediate-release tolvaptan in ADPKD. Kidney Int Rep. 2020;5:790–800. - PMC - PubMed

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