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A Phase 3 clinical trial of MLD-55 in pediatric patients with depression

A clinical trial of MLD-55 in pediatric patients with depression

128

In the open-label period, the proportion of males and females was 29.7% and 70.3%, respectively. The mean age at IC(SD, the same hereinafter) was 14.9(1.7) years. The baseline CDRS-R total score(at start of drug administration) was 65.8(13.5), and the baseline CGI-S(at start of drug administration) was 4.7(0.8). In the double-blind period, the proportion of males in the MLD-55 group and placebo group was 28.2% and 31.7%, respectively(same group order follows); and the proportion of females was 71.8% and 68.3%, respectively. The age at IC was 14.7(1.6) years and 15.0(1.9) years, respectively. The baseline CDRS-R total score(at start of double-blind period) was 26.7(5.2) and 26.8(5.2), respectively. The baseline CGI-S(at start of double-blind period) was 1.9(0.3) and 1.9(0.4), respectively.

The study drug was administered to 128 patients who completed the screening period and entered the open-label period. Of the 118 patients who reached week 12 of the open-label period, 80 patients met remission or response criteria and were randomized to the double-blind period(39 to MLD-55 and 41 to placebo). The most common reasons for discontinuation in the open-label period were incompatibility with the double-blind period continuation criteria of remission or response. The most common reason for discontinuation in the double-blind period were lack of efficacy of the investigational drug in both the MLD-55 and placebo groups.

In the open-label period, incidence of AEs and adverse drug reactions(ADRs) were 78.9% and 60.2%, respectively. The severity of most AEs was mild or moderate. Two patients experienced severe AEs, 1 patient experienced serious AEs and 6 patients experienced AEs leading to discontinuation. Of these, a causality relationship with the investigational drug could not be denied in 2 of the severe AEs, 1 of the serious AEs and 4 of the 6 AEs leading to discontinuation. In the double-blind period, AE incidence was 82.1% and 56.1% in the MLD-55 and placebo groups, respectively, and ADR incidence was 23.1% and 22.0%, respectively. The severity of most AEs was mild or moderate. In the MLD-55 group, 2 patients experienced severe AEs, 3 patients experienced serious AEs, and 2 patients experienced AEs leading to discontinuation, compared to none in the placebo group. None of these AEs were causally related to MLD-55.

The primary endpoint, time to relapse, showed no statistically significant difference between the MLD-55 and placebo groups(p=0.051, log-rank test). In the Cox proportional hazards model, the estimated hazard ratio[two-sided 95% confidence interval] for relapse in the placebo group versus the MLD-55 group was 2.96[0.94, 9.30].

The secondary endpoints, the relapse rate was 10.3% in the MLD-55 group and 26.8% in the placebo group, with no statistically significant difference between the two groups(p=0.085, Fisher's exact test). The mean change(SD, the same hereinafter) in CDRS-R total score from start of double-blind period to week 48(LOCF) was -2.1(11.4) in the MLD-55 group and 3.3(12.9) in the placebo group, a statistically significant lower value in the MLD-55 group compared with placebo(p= 0.048, ANCOVA). The change in CGI-S from start of double-blind period to week 48(LOCF) was -0.1(1.0) in the MLD-55 group and 0.4(1.1) in the placebo group, a statistically significant lower value in the MLD-55 group compared with placebo (p=0.025, ANCOVA). At week 48(WOCF), the rate of CGI-S worsening was 7.7% in the MLD-55 group and 34.1% in the placebo group, a statistically significant lower value in the MLD-55 group(p=0.005, Fisher's exact test).CGI-I at week 48(LOCF) was 1.6(1.0) in the MLD-55 group and 2.1(1.1) in the placebo group, a statistically significant lower value in the MLD-55 group compared with placebo(p=0.030, ANCOVA). The rate of improvement in CGI-I at week 48(LOCF) was 84.6% in the MLD-55 group and 70.7% in the placebo group, with no statistically significant difference between the groups(p=0.183, Fisher's exact test).

Superiority of MLD-55 over placebo for relapse prevention in Japanese adolescents 12 to 17 years of age with MDD could not be verified with time to relapse evaluated by log-rank test.

Dec. 07, 2023

https://www.liebertpub.com/doi/10.1089/cap.2023.0048

No

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Mochida Pharmaceutical Co., Ltd.

7, Yotsuya 1-chome, Shinjuku-ku, Tokyo 160-8515, Japan

clinical.trials.contact@mochida.co.jp

Mochida Pharmaceutical Co., Ltd.

7, Yotsuya 1-chome, Shinjuku-ku, Tokyo 160-8515, Japan

+81-3-3225-6303

webmaster@mochida.co.jp

completed

Feb. 15, 2019

Interventional

A multi-center, randomized, double-blind, placebo-controlled, parallel-group, study

treatment purpose

3

Patients with a primary diagnosis of major depressive disorder or persistent depressive disorder completely meeting the criteria of major depressive episode throughout the preceding 1 year according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)

(1)Patients with a complication or history of any of the following DSM-5-classified diseases:
- Bipolar and related disorders
- Schizophrenia spectrum and other psychotic disorders
(2)Patients with a history of suicidal behavior (suicide attempt, interrupted suicide attempts) based on C-SSRS within one year prior to screening.

Both

Major depressive disorder

investigational material(s)
Generic name etc : MLD-55
INN of investigational material : escitalopram
Therapeutic category code : 117 Psychotropic agents
Dosage and Administration for Investigational material : oral administration

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

safety
efficacy
- Efficacy
Time to relapse
- Safety
Adverse events

safety
efficacy
pharmacokinetics
- Efficacy
Relapse
Change in CDRS-R total score
- Safety
Adverse Reactions
- Pharmacokinetics
Plasma levels of escitalopram

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Sept. 21, 2018