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Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum (Quetiapine)

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ClinicalTrials.gov Identifier: NCT02978534
Recruitment Status : Recruiting
First Posted : December 1, 2016
Last Update Posted : December 1, 2016
Sponsor:
Information provided by (Responsible Party):
Crystal Clark, Northwestern University

Tracking Information
First Submitted Date November 22, 2016
First Posted Date December 1, 2016
Last Update Posted Date December 1, 2016
Study Start Date March 2016
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 28, 2016)
Change in plasma concentration/elimination [ Time Frame: 2 timepoints during pregnancy (second and third trimesters), and at four and twelve weeks postpartum ]
For patients taking the immediate release formulation, plasma levels will be obtained beginning at time 0 and at hours, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16. For patients on the extended release formulation, plasma levels will be obtained at time 0 and at hours 0.5, 1, 1.5, 2, 2,5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, and 24.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: November 28, 2016)
  • Arterial and Venous Umbilical Cord Concentration of Quetiapine and 7-N-desalylquetiapine [ Time Frame: 30 minutes ]
    Arterial and venous cord blood samples will be obtained immediately post-delivery and banked for later analysis
  • Cerebrospinal Fluid (CSF) Quetiapine and 7-N-desalkyquetiapine Concentrations [ Time Frame: CSF to be obtained within 10 minutes of the epidural placement during labor ]
  • Scores on Depression assessment, Inventory of Depression Symptomatology- Self Report (IDS-SR) [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum ]
    To determine if there is a pattern of increasing scores on self-report depression assessment (IDS-SR) and declining plasma levels. Increasing scores indicate worsening symptoms or depression episode recurrence.
  • Scores on anxiety scale, Generalized Anxiety Disorder (GAD-7) [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum ]
    To determine if there is a pattern of increasing scores on GAD-7 and declining plasma levels
  • Scores on mania assessment, Young Mania Reporting Scale (YMRS) [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum. ]
    To determine if there is a pattern of increasing scores on clinician administered mania assessment (YMRS) and declining plasma levels
  • Scores on Brief Psychosis Rating Scale (BPRS) [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum. ]
    assessment to evaluate psychotic symptoms
  • Positive responses on SAFTEE [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum. ]
    surveys general and specific side effects including somatic, behavioral, and affective symptoms
  • Delivery outcomes as determined by the Peripartum Events Scale (PES) [ Time Frame: 4 and 12 weeks postpartum ]
    assessment to quantify stressful events related to delivery.
  • Scores on the seperate domains of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum. ]
    Assesses patient perceptions in 5 domains:physical function, pain, emotional distress, social function, and fatigue.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum
Official Title Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum
Brief Summary The widespread and common use of quetiapine in childbearing and pregnant women demands more data to inform dosing and toxicity in pregnancy. The new FDA Pregnancy and Lactation Labeling Final Rule (PLLR) will go into effect on June 30th, 2015 and will replace the prior A, B, C, D, and X categories. Additionally, the PLLR will require information to aid prescribing decisions in three categories 1) Pregnancy (including labor and delivery), 2) Lactation, and 3) Females and Males of Reproductive Potential. The pregnancy category will include a subsection that will describe pharmacokinetic and pharmacodynamic characteristics of the medication in pregnancy, fetal risk, and data quality. The data collected in this study will update the FDA pregnancy pharmacokinetic section for quetiapine and inform physicians that prescribe to childbearing women.
Detailed Description

Bipolar Disorder (BD) and Schizophrenia (SCHZ) in pregnancy are associated with pregnancy complications and increased maternal mortality due to physiological and psychosocial changes independent of SGA use. Untreated BD and SCHZ have been associated with an increased risk of placental abnormalities, antepartum hemorrhage, preterm birth, pre-eclampsia, low birth-weight, intrauterine growth retardation, small for gestational age, fetal distress, neonatal hypoglycemia, stillbirth and congenital defects, and the potential for adverse neurodevelopmental outcomes. Severe maternal stress in pregnancy increases the risk for offspring mental disorders, and eye, ear, respiratory, digestive, skin, musculoskeletal, and genitourinary diseases and congenital malformations (i.e., cleft palate, cleft lip). Also, BD and SCHZ illness symptoms are linked to psychosocial consequences that result in poor perinatal outcomes including impulsivity that leads to reckless behavior such as increased indiscriminate sex and exposure to sexually transmitted infections, smoking, increased alcohol and drug use, less prenatal care, and poor nutrition. Furthermore, women with recurrence of mental illness in the perinatal period have increased risk for suicide, a leading cause of maternal death.

The only published case of quetiapine plasma concentrations in a pregnant woman included cross-sectional levels of a woman on 300 mg of quetiapine across pregnancy and postpartum. Compared to six months postpartum, the area under the curve decreased by 27%, 42%, and 18% in the first, second, and third trimester, respectively. Given the complexity of the metabolism of quetiapine to a very active metabolite, it is important to understand the altered metabolism of quetiapine and its active metabolite in pregnancy and the implication for dosing adjustments.

This study will investigate the longitudinal pharmacokinetics of quetiapine in pregnancy, delivery, and postpartum. The long-term goal of this line of research is to establish psychotropic medication dosing algorithms informed by longitudinal pharmacokinetic data to improve mental health and pregnancy outcomes for mothers with serious mental illness.

The primary aims are: 1) Determine the elimination clearance of quetiapine and its major active metabolite, 7-N-desalkyquetiapine, across pregnancy and postpartum; 2) Determine the effect of pharmacokinetic changes on symptoms and toxicity during pregnancy and postpartum, and; 3) Examine the maternal-to-cord plasma concentrations ratios of quetiapine and its major active metabolite, 7-N-desalkylquetiapine.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:

Blood serum specimen will be obtained to measure quetiapine and estradiol levels. Standard of care labs will be obtained on every participant that is eligible and signs informed consent. Participants will not have more than 50 ml of blood drawn every 8 weeks. Participants will also have the option to have blood drawn for DNA banking.

Participants in the study that elect to receive analgesia for pain related to labor and have a spinal-epidural at Northwestern University will have CSF stored and banked for future analysis.

Sampling Method Non-Probability Sample
Study Population Pregnant women taking quetiapine for the purpose of mood stabilizing will be recruited broadly from Northwestern clinical services, including Internal Medicine, OB/GYN, Family Medicine, and Psychiatry, registries, and from the local Chicagoland community. Patients that sign consent, complete the evaluation and meet criteria will be enrolled into the study.
Condition Bipolar Disorder
Intervention Drug: Quetiapine
Quetiapine concentrations will be observed in women who have already (under the guidance of a physician) decided to continue taking Quetiapine for the treatment of Bipolar Disorder (any subtype) or Schizophrenia during pregnancy.
Other Name: Seroquel
Study Groups/Cohorts Quetiapine
Patients taking quetiapine during pregnancy are eligible to participate in the study. Their dose and plasma concentration levels of quetiapine will be monitored throughout pregnancy and up to three months postpartum.
Intervention: Drug: Quetiapine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: November 28, 2016)
12
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 2020
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Age 18-45 years
  • Pregnant, second trimester
  • English-speaking
  • DSM-V diagnosis of Bipolar Disorder or Schizophrenia, any subtype
  • Medically healthy
  • Singleton gestation

Exclusion Criteria:

  • Chronic use of drugs for medical disorders, except thyroid replacement for stable hypothyroidism
  • No psychiatrist or obstetrician
  • QIDS-SR 16 positive answer 3 on item 12, "I have made specific plans for suicide or have actually tried to take my life" within the past week
  • DSM-V diagnosis of substance abuse or dependence in last 6 months, with the exception of cannabis; positive urine drug screen
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Rebecca L Newmark, BA 312-695-6010 rebecca.newmark@northwestern.edu
Contact: Crystal T Clark, MD, MSc 312-695-8648 crystal.clark@northwestern.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02978534
Other Study ID Numbers 00201540
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Crystal Clark, Northwestern University
Study Sponsor Northwestern University
Collaborators Not Provided
Investigators
Principal Investigator: Crystal T Clak, MD, MSc Northwestern University
PRS Account Northwestern University
Verification Date November 2016