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Pharmacokinetic Study Comparing Topical, Rectal, and Oral Quetiapine

Primary Purpose

Dementia, Delirium

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Quetiapine 25 mg gel applied topically

Quetiapine 25 mg tablet by mouth

Quetiapine 25 mg rectal suppository

Quetiapine 25 mg gel applied topically

About this trial

This is an interventional other trial for Dementia focused on measuring quetiapine, pharmacokinetics, dementia, delirium, palliative care

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Quetiapine

Arm Description

Quetiapine 25 mg

Outcomes

Primary Outcome Measures

Serum quetiapine levels after topical application (Visit 1)

Areas under the curve versus time

Serum quetiapine levels after oral administration (Visit 2)

Areas under the curve versus time

Serum quetiapine levels after rectal administration (Visit 3)

Areas under the curve versus time

Secondary Outcome Measures

Serum quetiapine levels after topical administration over 24 hours

Topical quetiapine applied every 4 hours for 24 hours

Full Information

NCT ID

NCT02131545

First Posted

May 1, 2014

Last Updated

April 21, 2017

Sponsor

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT02131545

Brief Title

Pharmacokinetic Study Comparing Topical, Rectal, and Oral Quetiapine

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Completed

Study Start Date

June 2014 (Actual)

Primary Completion Date

July 2016 (Actual)

Study Completion Date

July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dementia, Delirium

Keywords

quetiapine, pharmacokinetics, dementia, delirium, palliative care

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Quetiapine

Arm Type

Experimental

Arm Description

Quetiapine 25 mg

Intervention Type

Drug

Intervention Name(s)

Quetiapine 25 mg gel applied topically

Other Intervention Name(s)

Seroquel

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Quetiapine 25 mg tablet by mouth

Other Intervention Name(s)

Seroquel

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Quetiapine 25 mg rectal suppository

Other Intervention Name(s)

Quetiapine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Quetiapine 25 mg gel applied topically

Other Intervention Name(s)

Seroquel

Intervention Description

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

Primary Outcome Measure Information:

Title

Serum quetiapine levels after topical application (Visit 1)

Description

Areas under the curve versus time

Time Frame

8 hours

Title

Serum quetiapine levels after oral administration (Visit 2)

Description

Areas under the curve versus time

Time Frame

8 hours (no sooner than 72 hours from end of visit 1)

Title

Serum quetiapine levels after rectal administration (Visit 3)

Description

Areas under the curve versus time

Time Frame

8 hours (no sooner than 72 hours from end of visit 2)

Secondary Outcome Measure Information:

Title

Serum quetiapine levels after topical administration over 24 hours

Description

Topical quetiapine applied every 4 hours for 24 hours

Time Frame

24 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jonathan Leung, PharmD, RPh

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Pharmacokinetic Study Comparing Topical, Rectal, and Oral Quetiapine

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