Study of the Safety, Tolerability, and Pharmacokinetics of Once Weekly Zicronapine in Patients With Schizophrenia

Phase 2

Completed

• Conditions: Schizophrenia
• Interventions: Drug: Zicronapine 45 mg once weekly; Drug: Zicronapine 20 mg once weekly; Drug: Zicronapine 30 mg once weekly; Drug: Zicronapine open-label lead-in 10 mg daily; Drug: Zicronapine 10 mg daily

• Registration Number: NCT01377233
• Lead Sponsor: H. Lundbeck A/S

Brief Summary

The main purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of once weekly dosing of zicronapine, compared to daily dosing of zicronapine.

Detailed Description

The study includes 2 treatment periods. The open-label run-in period will begin at patient enrolment and continue for 3 weeks, during which all patients will receive once daily treatment with zicronapine. The double-blind period will begin at patient randomization and continue for 5 weeks, during which the patients will be assigned to one group receiving once daily treatment with zicronapine and 3 groups receiving once weekly treatment with zicronapine.

Study Timeline

• Study First Submitted: 2011-06-20
• Study First Submitted QC: 2011-06-20
• Study First Posted: 2011-06-21
• Study Start: 2011-07
• Primary Completion: 2012-02
• Disposition First Submitted: 2014-05-14
• Disposition First Submitted QC: 2014-05-14
• Disposition First Posted: 2014-05-28
• Results First Submitted: 2016-01-15
• Status Verified: 2016-02
• Results First Submitted QC: 2016-02-22
• Last Update Submitted: 2016-02-22
• Results First Posted: 2016-03-22
• Last Update Posted: 2016-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)
• A score of <=4 (moderately ill) on Clinical Global Impression - Severity of Illness (CGI-S) scale
• A total score >=60 on Positive and Negative Syndrome Scale (PANSS)
• A score of <=4 (moderate) on PANSS items: P7 (hostility) AND G8 (uncooperativeness)

Exclusion Criteria

• Acute exacerbation requiring hospitalization within the last 3 months OR requiring change of antipsychotic medication within the last 4 weeks
• Diagnosis or history of substance dependence or substance abuse according to DSM-IV-TR within the last 3 months
• Significant risk of harming himself/herself or others
• Positive serology for hepatitis A, B, C, or HIV
• Present condition that might compromise liver function
• Medical or neurological disorder or treatment that could interfere with study treatment or compliance
• Previous exposure to zicronapine

Other inclusion and exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zicronapine 45 mg once weekly	Zicronapine 45 mg once weekly	-
Zicronapine 20 mg once weekly	Zicronapine 20 mg once weekly	-
Zicronapine 30 mg once weekly	Zicronapine 30 mg once weekly	-
Zicronapine open-label lead-in 10 mg daily	Zicronapine open-label lead-in 10 mg daily	-
Zicronapine 10 mg daily	Zicronapine 10 mg daily	-

Primary Outcome Measures

Name	Time	Method
Number of Patients With Adverse Events as a Measure of Safety and Tolerability	11 weeks for open-label period; 13 weeks for double-blind period	Number of patients with treatment-emergent adverse events during each of the two study periods plus corresponding safety follow-up period. Open-label period: 3 weeks post-baseline plus 8 weeks safety follow-up (11 weeks total); Double-blind period: 5 weeks post-randomization plus 8 weeks safety follow-up (13 weeks total)

Secondary Outcome Measures

Name	Time	Method
Positive and Negative Syndrome Scale (PANSS) Total and Subscales Change From Baseline	8 weeks post-baseline (3 weeks open-label period plus 5 weeks double-blind period)	The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Clinical Global Impression Improvement Scale (CGI-I)	8 weeks post-baseline (3 weeks open-label period plus 5 weeks double-blind period)	The CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment is made independent of whether the rater believes the improvement is drug-related or not.
Clinical Global Impression Severity Scale (CGI-S) Change From Baseline	8 weeks post-baseline (3 weeks open-label period plus 5 weeks double-blind period)	The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses their clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients).

Trial Locations

Locations (4)

US001; 🇺🇸 Rockville, Maryland, United States

US004; 🇺🇸 San Diego, California, United States

US003; 🇺🇸 National City, California, United States

US002; 🇺🇸 Garden Grove, California, United States