Diazoxide Choline Extended-release Tablets in Prader-Willi Syndrome: A Randomized, Double-blind, Withdrawal Period Study.

Background

We assessed the efficacy and safety of diazoxide choline extended-release (DCCR) tablets for the treatment of hyperphagia in adults and children four years of age and older with Prader-Willi syndrome.

我们评估了二氮嗪胆碱缓释（DCCR）片剂治疗4岁及以上普拉德-威利综合症患者过度进食的疗效和安全性。

Methods

We conducted a 16-week, randomized withdrawal study in children and adults with Prader-Willi syndrome and hyperphagia.

我们开展了一项为期16周的随机撤药研究，研究对象为患有普拉德-威利综合征和暴食症的儿童及成人。

Participants who previously completed randomized (13-week DCCR or placebo) and open-label (2.5-4.5 years DCCR) studies were randomized 1:1 to receive once-daily DCCR or placebo.

先前完成随机（13周DCCR或安慰剂）和开放标签（2.5-4.5年DCCR）研究的参与者被随机1:1分配，每天一次接受DCCR或安慰剂。

The primary endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total score change from baseline to 16 weeks.

主要终点是临床试验过食问卷（HQ-CT）总分从基线到16周的变化。

Secondary endpoints included Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I); exploratory endpoints included weight and body mass index (BMI) z-score.

次要终点包括临床总体印象严重程度（CGI-S）和改善（CGI-I）；探索性终点包括体重和体质指数（BMI）z分数。

Results

Seventy-seven participants were randomized (DCCR:38; placebo:39).

共有77名参与者被随机分配（DCCR：38人；安慰剂：39人）。

Statistically significant increases in HQ-CT from baseline to week 16 were observed with placebo vs DCCR [least square (LS) mean (standard error) change 7.6 (1.09)] with placebo and 2.6 (1.12) with DCCR; P = .0022.

从基线到第16周，与DCCR相比，安慰剂组的HQ-CT显示出统计学上显著的增加[最小二乘（LS）均值（标准误）变化安慰剂为7.6（1.09），DCCR为2.6（1.12）；P = .0022]。

CGI scores favored DCCR but were not significantly changed.

CGI评分倾向于DCCR，但变化不显著。

Consistent with the hyperphagia response, the placebo cohort gained more weight and increased their BMI z-score more than the DCCR cohort [LS mean weight difference (95% confidence interval) -1.6 kg (-3.1, -0.1)]; LS mean z-score difference was -0.09 (-0.17, -0.01).

与过度进食反应一致，安慰剂组比DCCR组体重增加更多，BMI z分数增加更多[最小二乘法平均体重差异（95%置信区间）-1.6公斤（-3.1，-0.1）]；最小二乘法平均z分数差异为-0.09（-0.17，-0.01）。

Adverse events were similar with both treatments, with no serious adverse events in the DCCR arm.

两种治疗的不良事件相似，DCCR组中没有严重不良事件。

Conclusions

Continued DCCR treatment was superior to placebo for hyperphagia.

持续使用DCCR治疗对于治疗贪食症优于安慰剂。

DCCR appears to offer meaningful therapeutic benefits for people with Prader-Willi syndrome.

DCCR似乎为患有普拉德-威利综合症的人群提供了有意义的治疗益处。