The Significance of Deviation in Time From the 12-hour Standard Serum-clozapine Monitoring.

The Significance of Deviation in Time From the 12-hour Standard Serum-clozapine Monitoring

The role of Therapeutic Drug Monitoring (TDM) in clozapine dose adjustment have been debated. Blood samples for s-clozapine monitoring should be drawn 12 hours post dose.

The scope of this trial is to describe changes of s-clozapine and s-N-desmethyl-clozapine within the range of 10-14 hours after the last administration of clozapine .

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Procedure: Blood sampling; Drug: Clozapine

Detailed Description

Several factors can influence s-clozapine and thereby the occurence of dose-related adverse reactions and level of treatment response. The role of Therapeutic Drug Monitoring (TDM) in clozapine dose adjustment have been debated. Blood samples for s-clozapine monitoring are recommended to be drawn 12 hours post dose. Uncertainty regarding the timing of blood sampling and the individual pharmakokinetics for clozapine +/- 2 hours from the 12-hour timepoint, leads to uncertainty regarding the comparability of serum concentrations and the information hold within them.

The scope of this trial is to describe changes of s-clozapine and s-N-desmethyl-clozapine within the range of 10-14 hours after the last administration of clozapine .

In addition we want to investigate if any of the following covariates might affect the change of s-clozapine and s-N-desmethyl-clozapine: Sex, age, BMI, co-medications, signs of infection, caffeine intake and smoking.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • København Ø
    • Copenhagen, København Ø, Denmark, 2100
      • Psychiatric Centre Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 < 65
• Diagnosed with schizophrenia according to the criteria of ICD10 (International Classification of Diseases, World Health Organization) or the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the American Psychiatric Association)
• Unchanged dose of clozapine for the last 30 days
• Usual time of clozapine evening-dose administration between 9 and 12 pm.

Exclusion Criteria:

• Significant drug or alcohol abuse that affects participation in this trial
• Non- or partial compliance of clozapine the day before the trial (assessed by interview)
• Unresponsive by telephone the evening before the trial
• Consumption of clozapine in the morning on the day of the trial
• Significant change in smoking habits within the last 30 days (assessed by interview)
• Significant change of caffeine intake within the last 7 days (assessed by interview)
• Modified use of other antipsychotics within the last 30 days
• Within the last 30 days (7 days for hormone based contraceptives) changes in the use of other medications that can affect s- clozapine during the trial : ( fluvoxamine, ciprofloxacin, hormone based contraceptives, carbamazepine , phenytoin , rifampicin, omeprazole )
• Females who are pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clozapine; treatment as usual: administration of clozapine between 9 and 12 pm. Blood sampling 10 -14 hours post drug administration	Procedure: Blood sampling; blood samples for s-clozapine and s-desmethyl-clozapine analysis are collected at 10, 11, 12, 13 and 14 hours post evening-clozapine-administration; Drug: Clozapine; Registration of the exact time of drug administration. Also postponement of any morning clozapine administration until ended blood sampling.; Other Names: Leponex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage change in serum-clozapine	10 - 14 hours post drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage change in serum-clozapine (multiple shorter ranges)	< 10 -14 hours post dose

Collaborators and Investigators

• Sponsor: Anders Fink-Jensen, MD, DMSci
• Collaborators: Rigshospitalet, Denmark; University of Copenhagen

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: November 13, 2015
• First Submitted That Met QC Criteria: December 6, 2015
• First Posted (Estimate): December 9, 2015

Study Record Updates

• Last Update Posted (Estimate): February 25, 2016
• Last Update Submitted That Met QC Criteria: February 24, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Schizophrenia, Clozapine, TDM, Serum Concentration
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; GABA Agents; GABA Antagonists; Clozapine
• Other Study ID Numbers: CLO-MEAS; 2015-002520-82 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO