Double-Blind, Randomized, Placebo-Controlled Trial of DA-9701 in Parkinson's Disease: PASS-GI Study

Ji-Hyun Choi, Jee-Young Lee, Jin Whan Cho, Seong-Beom Koh, Young Soon Yang, Dalla Yoo, Cheol-Min Shin, Hee Tae Kim, Ji-Hyun Choi, Jee-Young Lee, Jin Whan Cho, Seong-Beom Koh, Young Soon Yang, Dalla Yoo, Cheol-Min Shin, Hee Tae Kim

Abstract

Objectives: This study aimed to assess the efficacy of DA-9701 on gastrointestinal symptom-related quality of life in patients with Parkinson's disease on stable dopaminergic medications.

Methods: This multicenter, double-blind, placebo-controlled, phase 4 trial included a total of 144 patients with Parkinson's disease with gastrointestinal dysfunctions based on predefined criteria. Participants were randomized to take either DA-9701 or placebo for 4 weeks, and then both groups were administered DA-9701 for an additional 8 weeks while antiparkinsonian medications were unchanged. The primary outcome measure was gastrointestinal symptoms and related quality-of-life changes assessed on the Korean Nepean dyspepsia index after 4 and 12 weeks of therapy. We also evaluated the impact of DA-9701 therapy on parkinsonian motor symptoms at each time point.

Results: The gastrointestinal symptom-related quality-of-life score significantly improved in the DA-9701-treated group compared with the placebo-treated group after 4weeks (adjusted P = 0.012 by linear mixed effect model analysis). The overall gastrointestinal symptom and dyspepsia sum scores improved at 12 weeks after intervention in the DA-9701-first treated group (adjusted P = 0.002 and 0.014, respectively) and also in the placebo-first treated group (adjusted P = 0.019 and 0.039) compared with the baseline. Parkinsonian motor severity was not significantly affected by DA-9701 treatment in both groups at 4 and 12 weeks after intervention. There were no drug-related serious adverse events throughout the trial.

Conclusions: DA-9701 therapy improved gastrointestinal symptom-related quality of life, and 12 weeks of daily administration can relieve the overall severity of gastrointestinal symptoms in patients with Parkinson's disease without affecting motor symptoms. (Clinical trial identifier: NCT02775591.) © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: DA-9701; Parkinson's disease; double-blind randomized controlled trial; gastrointestinal dysfunction; quality of life.

© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Figures

FIG. 1.
FIG. 1.
Flowchart of study subjects. We screened a total of 150 participants. Among them, 65 participants in each DA‐9701 and placebo arm (a total of 130 participants) completed the first 4 weeks’ parallel intervention; 55 participants of the DA‐9701‐first and 58 participants of the placebo‐first groups (a total of 113 participants) completed all study visits.
FIG. 2.
FIG. 2.
Gastrointestinal symptoms and related QoL change after intervention. The efficacy of DA‐9701 was demonstrated in the NDI‐K QoL scores at 4 weeks compared with the placebo (adjusted P = 0.023 by a linear mixed effect model analysis). Time changes at 4 and 12 weeks in the NDI‐K QoL scores were significant in the DA‐9701 group. There were also significant time changes in the NDI‐K total symptom scores and dyspepsia sum scores in the DA‐9701 group at 12 weeks. The placebo group also showed significant time changes in the NDI‐K symptom total score and dyspepsia scores after an additional 8 weeks of DA‐9701 therapy while maintaining double blindness until the end of the trial. P values provided in each figure are comparisons between DA‐9701 and the placebo groups at 4 weeks. Asterisks designate statistically significant temporal changes in the scores in each group: * < 0.05, ** < 0.01, *** < 0.001. NDI‐K, The Nepean Dyspepsia Index–Korean version; QoL, quality of life.
FIG. 3.
FIG. 3.
Parkinsonian symptoms and PD‐related quality of life after intervention. The UPDRS motor score and the K‐PDQ39 summary index changes were not different between DA‐9701 and the placebo groups at 4 weeks (4W). There were also no significant temporal changes in the UPDRS motor scores in both groups at 4 and 12 weeks (12W). The scores in the bodily discomfort domain of K‐PDQ39 showed a tendency of improvement at 12 weeks in the DA‐9701 group but without significance with Bonferroni correction. P values provided in each figure are comparisons between DA‐9701 and the placebo groups at 4 weeks. Asterisks designate statistically significant temporal changes in the scores in each group. B0, baseline; PD, Parkinson's disease, K‐PDQ39, Korean version 39‐item Parkinson's Disease Questionnaire; UPDRS, Unified Parkinson's Disease Rating Scale.

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