Pharmacokinetic Study Comparing Topical, Rectal, and Oral Quetiapine

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT02131545

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Quetiapine, a second generation antipsychotic, is only available as oral tablets. However, topical and rectal formulations have been produced in compounding pharmacies. There is no data available suggesting that topical or rectal formulations provide serum levels similar to oral medication. In the clinical setting, when oral administration of quetiapine is not possible (for example, when a patient is extremely ill physically or mentally or both), clinicians and pharmacists have collaborated in such cases and have at times had to administer quetiapine compounded in other dosage formulations such as rectal or topical formulations. Despite clinical effectiveness of these other formulations, there are no available studies that have investigated blood levels of the drug other than the oral form. The investigators are therefore designing this pharmacokinetic study to evaluate the the systemic absorption of quetiapine in oral, rectal and topical formulations. If the investigators are able to demonstrate detectable levels from rectal and topical quetiapine formulations compared to the oral form, this knowledge will enhance clinical psychiatric practice by providing a more broad route of administration for quetiapine which is a commonly used drug for psychiatric symptoms.

Condition or Disease	Intervention/Treatment	Phase
Dementia Delirium	Drug: Quetiapine 25 mg gel applied topically Drug: Quetiapine 25 mg tablet by mouth Drug: Quetiapine 25 mg rectal suppository Drug: Quetiapine 25 mg gel applied topically	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

A Single Dose Pharmacokinetic Study of Topical and Rectal Quetiapine Compared to Oral Quetiapine in Healthy Adults

Actual Study Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Jul 1, 2016

Actual Study Completion Date :

Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Quetiapine Quetiapine 25 mg	Drug: Quetiapine 25 mg gel applied topically Quetiapine 25 mg gel applied topically; 9 serum quetiapine levels drawn over the course of 8 hours Other Names: Seroquel Drug: Quetiapine 25 mg tablet by mouth Quetiapine 25 mg tablet administered by mouth; 9 serum quetiapine levels drawn over the course of 8 hours Other Names: Seroquel Drug: Quetiapine 25 mg rectal suppository Quetiapine 25 mg suppository administered rectally; 9 serum quetiapine levels drawn over the course of 8 hours Other Names: Quetiapine Drug: Quetiapine 25 mg gel applied topically Quetiapine 75 mg gel applied topically every 4 hours for 24 hours; 6 serum quetiapine levels drawn over the course of 24 hours Other Names: Seroquel

Arm

Intervention/Treatment

Experimental: Quetiapine

Quetiapine 25 mg

Drug: Quetiapine 25 mg gel applied topically

Quetiapine 25 mg gel applied topically; 9 serum quetiapine levels drawn over the course of 8 hours

Other Names:

Seroquel

Drug: Quetiapine 25 mg tablet by mouth

Quetiapine 25 mg tablet administered by mouth; 9 serum quetiapine levels drawn over the course of 8 hours

Other Names:

Seroquel

Drug: Quetiapine 25 mg rectal suppository

Quetiapine 25 mg suppository administered rectally; 9 serum quetiapine levels drawn over the course of 8 hours

Other Names:

Quetiapine

Drug: Quetiapine 25 mg gel applied topically

Quetiapine 75 mg gel applied topically every 4 hours for 24 hours; 6 serum quetiapine levels drawn over the course of 24 hours

Other Names:

Seroquel

Outcome Measures

Primary Outcome Measures

Serum quetiapine levels after topical application (Visit 1) [8 hours]
Areas under the curve versus time
Serum quetiapine levels after oral administration (Visit 2) [8 hours (no sooner than 72 hours from end of visit 1)]
Areas under the curve versus time
Serum quetiapine levels after rectal administration (Visit 3) [8 hours (no sooner than 72 hours from end of visit 2)]
Areas under the curve versus time

Secondary Outcome Measures

Serum quetiapine levels after topical administration over 24 hours [24 hours]
Topical quetiapine applied every 4 hours for 24 hours

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy adult volunteers (18-65 years old) willing to undergo a general health screen consisting of blood pressure, heart rate, respiratory rate, height, weight, temperature, and electrocardiogram will be identified.
The below parameters must be met to be consider an adult healthy to volunteer for inclusion in this study:
Blood pressure less than 160/99 mmHg and greater than 105/50 mmHg
Heart rate between 50-100 beats per minutes
Respiratory rate between 10-30 breaths per minute
Temperature between 34 °C and 37.5°F
Corrected QT interval of < 470 msec
Liver function tests less than 1.5 times the upper limit of normal
Estimated creatinine clearance (estimated by Cockcroft Gault formulation) greater than 60 mL/min
Female participants will complete a urine pregnancy test that must result in a negative finding

Exclusion:

Allergy to quetiapine, Lipoderm or polyethylene glycol
Currently taking quetiapine
Pregnant, planning to become pregnant or breast feeding
Over or under 30% of ideal body weight
History of or active cardiovascular disease (except hypertension meeting the inclusion criteria for blood pressure), severe kidney disease (i.e. needing dialysis), or liver disease
History of schizophrenia, bipolar disorder, substance use disorders (but excluding nicotine use disorders and stable unipolar depression (See below))
Unstable unipolar depression, defined as hospitalization for depression within 1 year or changes to an antidepressant regimen within 6 months
History of seizure or seizure disorder
Parkinson's disease, Huntington's disease, tardive dyskinesia or other diagnosed movement disorder
History of/or active hematologic/oncologic illness
Dementia
Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome
History of organ transplant
History of gastric bypass
Contraindications for suppository administration
With Ostomy, chronic diarrhea
Diabetes, type 1 or type 2
Prolong corrected QT interval (>470 msec) or history of congenital long QT syndrome
Open wound(s) or unhealed wound(s) at topical medication application site (anterior forearm)
Active or latent tuberculous and currently prescribed pharmacotherapy treatments
Currently prescribed or taken with in the last 7 days, medications which have a known interaction with quetiapine or compound the risk of adverse events associated with quetiapine:

QTc prolonging medications:
Antipsychotics
Vaughan Williams Class IA, IB, IC, III antiarrhythmics
Anti-infective agents (excluding topical agents, oral penicillins, oral cephalosporins)
Antiemetics
Methadone
Cisapride
Cimetidine
Divalproex sodium/valproic acid
Tetrabenazine
Solifenacin
Tricyclic antidepressants
Tizanidine
Fingolimod
Increase quetiapine concentrations, not previously mentioned
Paroxetine
Fluoxetine
Fluvoxamine
Non-dihydropyridine calcium channel blockers (verapamil, diltiazem)
Tamoxifen
Cyclosporin (excluding ophthalmic formulation)
Nefazodone
Decrease quetiapine levels, not previously mentioned
Bosentan
Carbamazepine
Glucocorticoids
Modafinil
Primidone
St. John's wort
Barbiturates
Phenytoin

Vulnerable populations will be excluded (i.e. prisoners, wards of the state, emancipated minors, children, pregnant women)
Inability to receive telephone calls for the purpose of post-intervention follow-up
Inability or unwillingness of individual to give written informed consent
Non-English speaking populations