QUVIVIQ® Pregnancy Registry (ID-078A403)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Other
• If ‘other’, further details on the scope of the study:
  Pregnancy exposure registry
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  QUVIVIQ
• Study drug International non-proprietary name (INN) or common name:
  DARIDOREXANT HYDROCHLORIDE
• Anatomical Therapeutic Chemical (ATC) code:
  (N05CJ03) daridorexant

  daridorexant
• Medical condition to be studied:
  Maternal exposure during pregnancy

  Maternal exposure before pregnancy
• Additional medical condition(s):
  Major congenital malformations

Population studied

• Short description of the study population:
  Women with insomnia disorder, monitored in a standard-of-care setting, and pregnant at time of enrollment (prospective pregnancies) will be assigned to a specific cohort according to the insomnia medication received. Women with insomnia disorder for whom the outcome of pregnancy is known prior to enrollment (retrospective pregnancies) will be analyzed in a separate case series.
• Age groups:
  Neonate

  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  Adolescents (12 to < 18 years)

  Adults (18 to < 65 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  785

Study design details

• Study design:
  International, longitudinal, observational, prospective study.; Data collection: women’s health, adverse events, pregnancy complications and -outcomes, malformations of the infants and other outcomes.; Infants will be followed for 52 weeks after birth; maximal study duration for women is 21 months.
• Main study objective:
  The primary objective is to compare the prevalence of major congenital malformations among prospective pregnancies in women with insomnia exposed to QUVIVIQ during pregnancy (Cohort A) and women exposed to other, non-orexin receptor antagonist medications for insomnia during pregnancy (Cohort B1).
• Setting:
  Primary data will be collected from pregnant women with insomnia in a standard-of-care setting, where participants are seen regularly by their treating healthcare providers either for insomnia treatment or for regular assessment after insomnia treatment.; ; The data will be provided by the participants and healthcare providers (e.g., primary care provider, insomnia specialist, psychiatrist, obstetrician, nurse, midwife, pediatrician). ; ; Women will be followed from enrollment through the end of their pregnancy and up to 52 weeks after the infant’s birth. Infants will be followed for 52 weeks after birth. Maternal outcomes during the postpartum follow-up year (aside from safety surveillance and lactation information from breastfeeding mothers) will not be collected. ; ; There will be 3 study cohorts: ; ; Cohort A; Women with insomnia exposed to QUVIVIQ during pregnancy or within 5 half-lives prior to conception.; ; Cohort B1; Women exposed to other, non-orexin receptor antagonist medications for insomnia during pregnancy or within 5 half-lives of the respective insomnia medication prior to conception.; ; Cohort B2; Women who had no exposure to any insomnia medication during pregnancy and within 5 half-lives of any insomnia medication taken prior to conception.
• Comparators:
  Non-orexin receptor antagonist medications for insomnia (Cohort B1); No insomnia medication (Cohort B2)
• Outcomes:
  Primary outcome measure:; 1. Major congenital malformations; ; Secondary outcome measures:; 2. Pregnancy complications - pre-eclampsia; 3. Pregnancy complications - pregnancy-induced hypertension; 4. Pregnancy complications - pre-term labor; 5. Pregnancy complications - gestational diabetes; 6. Pregnancy outcomes - elective or therapeutic pregnancy termination; 7. Pregnancy outcomes - spontaneous abortion; 8. Pregnancy outcomes - fetal death or stillbirth; 9. Pregnancy outcomes - live birth; 10. Pregnancy outcomes - pre-term birth; 11. Infant outcomes - minor congenital malformations; 12. Infant outcomes - size for gestational age; 13. Infant outcomes - low birth weight; 14. Infant outcomes - infant death; 15. Infant outcomes - hospitalization for serious illness; 16. Infant outcomes - postnatal growth and development
• Data analysis plan:
  1. Prospective pregnancies - outcome of pregnancy not known at the time of enrollment:; • In the primary analysis, the prevalence of major congenital malformations in infants of women with insomnia exposed to QUVIVIQ during pregnancy or within 5 half-lives prior to conception (Cohort A) will be compared to the prevalence in infants of women unexposed to QUVIVIQ but exposed to other, non-orexin receptor antagonist medications for insomnia during pregnancy or within 5 half-lives of the respective insomnia medication prior to conception (Cohort B1). The primary analysis will use risk ratios (one-sided 97.5% CI) to compare major congenital malformations in infants between Cohort A and Cohort B1 among women with first trimester exposure to their respective insomnia medications. Women exposed to QUVIVIQ who take other medications for insomnia at any time during pregnancy will be excluded from the primary analysis. Women with known teratogen exposure during pregnancy will be included in the primary analysis.; • In a secondary analysis, the prevalence of major congenital malformations in the infants of Cohort A will be compared to the prevalence in infants of Cohort B2 (women who had no exposure to any insomnia medication during pregnancy and within 5 half-lives of any insomnia medication taken prior to conception), as well as to infants of the overall comparator cohort (Cohort B).; ; 2. Retrospective pregnancies - outcome of pregnancy known prior to enrollment:; • Women with insomnia exposed to QUVIVIQ during pregnancy or within 5 half-lives prior to conception, for whom the outcome of pregnancy was known prior to enrollment, will be analyzed in a separate case series. Analyses in this case series will primarily be qualitative.