Safety and Tolerability Study of Lu AF35700 After Repeated Dosing in Patients With Schizophrenia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the tolerability and safety of Lu AF35700 after repeated oral dosing to patients with schizophrenia.

Official Title
-----------------
Interventional, Randomised, Double-blind, Placebo-controlled, Sequential Group, Multiple Dose Study Investigating the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of Lu AF35700 in Patients With Schizophrenia

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Drug: Lu AF35700
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men or women between 18 and 60 years (extremes included) BMI of ≤38 Primary diagnosis of schizophrenia according to DSM-IV-TR™ (codes 295.10, 295.20, 295.30, 295.90) Clinical Global Impression - Severity of Illness (CGI-S) score ≤4 (moderately ill) at screening and baseline PANSS total score ≤80 Score ≤4 (moderate) on the following PANSS items at screening and safety baseline: P7 (hostility), G8 (uncooperativeness) Willing to be hospitalised for 4 to 5 weeks after the Safety Baseline Visit Exclusion Criteria: The patient experienced an acute exacerbation requiring hospitalization within the last 6 months The patient experienced an acute exacerbation requiring change in antipsychotic medication (with reference to drug or dose) within the last 4 weeks The patient has a diagnosis or history of substance dependence (except nicotine) or substance abuse according to DSM-IV-TR® criteria ≤3 months prior to screening The patient smokes >20 cigarettes per day Other protocol-defined inclusion and exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lu AF35700 oral solution (1 mg/mL)<br>Planned daily doses range from 5 mg/day to 30 mg/day for 3 weeks. Weekly doses up to 75 mg/week for 3 weeks. | Drug: Lu AF35700<br> <br> |
| Placebo Comparator: Matching placebo<br>Oral solution | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute values and change from baseline in safety variables (Adverse events, clinical safety laboratory tets, vital signs, weight, and ECG) |  | Screening to day 78 (up to 8 weeks after last dose) | 
| Change from baseline in AIMS, BARS and SAS Total score | Abnormal movement rating scale | Baseline to day 21 | 
| Columbia Suicide Severity Rating Scale (C-SSRS) |  | Sceening to day 78 (up to 8 weeks after last dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day 21 area under the Lu AF35700 and Lu AF36152 plasma concentration-time curve from 0-24 hours post dose (AUC0-tau) in a daily dosing regime |  | Day 21 in the dosing period | 
| Maximum observed concentration (Cmax) of Lu AF35700 and Lu AF36152 |  | Day 1 and 21 in the dosing period | 
| Half-lives (t½) of Lu AF35700 and Lu AF36152 |  | Day 1 and 21 in the dosing period | 
| Day 14-21 area under the Lu AF35700 and LuAF36152 plasma-concentration-time curve from 0-168 hours post-dose (AUCtau) in a weekly dosing regimen |  | Day 14-21 in the dosing period |