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PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFECTS OF RO6889450 (RALMITARONT) IN PATIENTS WITH SCHIZOPHRENIA OR SCHIZOAFFECTIVE DISORDER AND NEGATIVE SYMPTOMS

BP40283

104

This study was conducted at 45 centers in 4 countries, which were United States, Ukraine, Japan and Spain.

104 participants were randomized 1:1:1 to RO6889450 45 mg, RO6889450 150 mg, or placebo (prior to protocol v.5; RO6889450 45 mg arm was removed thereafter), or RO6889450 150 mg, RO6889450 300 mg, or placebo (after protocol v.5) for 12 weeks in addition to their usual antipsychotic therapy.

Overall, RO6889450 at a dose of 45 mg QD, 150 mg QD and 300 mg QD was considered safe and well tolerated in this study in participants with schizophrenia. The most frequently reported AEs (>=5% in RO6889450 45 mg/150 mg/300 mg group) were lip pain, fatigue, non-cardiac chest pain, nasopharyngitis, upper respiratory tract infection, pain in extremity, dizziness, dizziness postural, rash. Most AEs were considered mild or moderate.

Primary outcome measures: Although the primary endpoint for efficacy in this study was change from baseline at Week 12 in the BNSS avolition/apathy subscore, change from baseline in the PANSS-NSFS score was used as the primary endpoint for the interim analysis. Results of the interim analysis did not show a treatment benefit of RO6889450 compared to placebo. There was no difference in terms of the primary or secondary efficacy endpoints. Secondary outcome measures: See above

Results of the interim analysis did not show a treatment benefit of RO6889450. RO6889450 at a dose of 45 mg, 150 mg and 300 mg was considered safe and well tolerated in this study in participants with schizophrenia. The observed RO6889450 concentrations and the population PK model-predicted PK parameters were within the expected range based on previous clinical studies.

No

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https://jrct.mhlw.go.jp/latest-detail/jRCT2031200287

Clinical trials information

Chugai Pharmaceutical Co., Ltd.

1-1 Nihonbashi-Muromachi 2-Chome, Chuo-ku Tokyo

clinical-trials@chugai-pharm.co.jp

Clinical trials information

Chugai Pharmaceutical Co., Ltd.

1-1 Nihonbashi-Muromachi 2-Chome, Chuo-ku Tokyo

+81-120-189-706

clinical-trials@chugai-pharm.co.jp

Complete

Jan. 31, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. Patients with a DSM-5 diagnosis of schizophrenia or schizoaffective disorder as confirmed by the MINI
2. Stable treatment with a D2/5HT2A antagonist or pure D2 antagonists, or a D2 partial agonist for a minimum of six months and receiving no more than two antipsychotics
3. Medically stable during the prior three months
4. Participant is an outpatient with no psychiatric hospitalizations within the prior six months
5. PANSS-NSFS of 18 or higher
6. The following rating on items of the PANSS: (a) less than 5 on G8 (uncooperativeness), P1 (delusions), P3 (hallucinations), P4 (excitement/hyperactivity), and P6 (suspiciousness/persecution); (b) less than 4 on P7 (hostility), and G14 (poor impulse control)
7. Has an informant who is considered reliable by the Investigator
8. BMI between 18-40 kg/m2 inclusive
9. A woman is eligible to participate if she is not pregnant, not breastfeeding, and agrees to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 28 days after the last dose of study drug

1. Moderate to severe substance use disorder within six months (excluding nicotine) as defined by DSM-5
2. Any ESRS-A CGI subscore greater than or equal to 3
3. Other current DSM-5 diagnosis (e.g., bipolar disorder, major depressive disorder)
4. PANSS item G6 (depression) greater than or equal to 5
5. Significant risk of suicide or harming him- or herself or others according to the Investigator's judgment
6. A prior or current general medical condition that might be impairing cognition or other psychiatric functioning
7. Positive result at screening for hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or HIV-1 and HIV-2. HCV antibody positive participants are eligible if HCV RNA is negative
8. Tardive dyskinesia that is moderate to severe or requires treatment
9. History of neuroleptic malignant syndrome
10. Average triplicate QTcF interval greater than 450 msec for males and 470 msec for females or other clinically significant abnormality on screening ECG based on centralized reading
11. Clinically significant abnormalities in laboratory safety test results
12. Significant or unstable physical condition that in the investigator's judgment might require a change in medication or hospitalization during the course of the study
13. On more than one antidepressant, or if on one antidepressant, a change in dose within 28 days prior to screening
14. History of clozapine treatment
15. History of treatment with electroconvulsive therapy (ECT)
16. Concomitant use of prohibited medications
17. Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenomorphine, methadone, cannabinoids, cocaine, and barbiturates
18. Receipt of an investigational drug within 28 days or five times the half-life of the investigational drug (whichever is longer) before the first study drug administration
19. Donation of blood over 400 mL within three months prior to screening
20. Diagnosis of COVID-19 infection (confirmed or presumptive) 4 weeks prior to screening or during screening. Participants can be re-screened after 4 weeks of full recovery in addition to Investigator and/or institutional approval to enroll

Both

Schizophrenia

RO6889450:150 mg or 300 mg QD
placebo:QD

Efficacy
BNSS

Safety, Efficacy, Phamacokinetics
CGI-S, CGI-I, PANSS, BNSS, DPAS, Observation, PK

+81-3-5213-0028

June. 26, 2020

United States/Spain/Ukraine