A Multicenter Trial of the Efficacy and Safety of Diclegis® for Nausea and Vomiting of Pregnancy in Pregnant Adolescents

This is a multicenter study in the treatment of NVP that will actively recruit pregnant
adolescents from approximately 14-16 study sites in the United States and Canada. After
obtaining informed consent on Day 1, a medical examination will be conducted to ensure
eligibility. Participants will be randomized to receive Diclegis or placebo. On Day 1, all
participants will take 2 tablets of study drug at bedtime. On Days 2 to 14, participants
will take 2 tablets of study drug at bedtime. The minimum dosage will be 2 tablets daily at
bedtime, increasing, when indicated, to the maximal dosage of 4 tablets per day on Days 3 to
14. Participants will be required to complete a diary daily to assess the severity of their
NVP by using the validated Pregnancy Unique Quantification of Emesis (PUQE) and to record
any AEs experienced; the Global Assessment of Well being scale will be completed only on
Days 1, 8 and 15. Participants will receive telephone calls daily to assess whether the
current dosing regimen is sufficient at relieving NVP symptoms, to review study procedures,
and to address her questions/concerns. Participants will return to the clinic for evaluation
on Day 4 (±1 day) and Day 15 (±1 day) for an end of study visit.

Eligible participants are those between 12 and 17 years of age, pregnant with a gestational
age of 7 to 15 weeks + 0 days, suffering from NVP, with a PUQE score ≥6, and who have not
responded to conservative management consisting of dietary/lifestyle advice according to the
2004 American College of Obstetrics and Gynecology (ACOG) Practice Bulletin.

Inclusion Criteria:

1. The participant is a pregnant female between the following ages: at least 12 years on
the day of recruitment (ie, Day 1) and not yet 18 years on the last day of the study
(ie, Day 15).

2. The participant must provide written informed consent and/or assent to participate in
the study, and agrees that she will follow dosing instructions and complete all
required study visits.

3. The participant's entry ultrasound indicates a viable pregnancy and confirms
gestational age of the fetus is 7-15 weeks + 0 days at the anticipated time of the
first dose of study drug provided that her NVP symptoms began If an ultrasound was performed within 4 weeks of the study entry visit, and results
can be obtained, an additional ultrasound is not necessary.

4. The participant is suffering from NVP and has a PUQE score ≥6.

5. The participant has not responded to conservative management consisting of
dietary/lifestyle advice according to the 2004 ACOG Practice Bulletin.

6. The participant agrees, if on a multivitamin, to continue on her current dose of
multivitamin for the duration of the trial.

7. The participant does not plan termination of the pregnancy.

8. On the basis of medical history, physical examination and screening laboratory tests,
the participant is judged to be in good health.

9. The participant must be able to swallow the study drug whole (ie, without splitting,
crushing, or chewing the tablets).

Exclusion Criteria:

1. The investigator confirms the participant's nausea and vomiting is of etiology other
than NVP.

2. The participant has gestational trophoblastic disease or multifetal gestation.

3. The participant has a condition for which antihistamines, in the opinion of the
investigator, are contraindicated (eg, epilepsy, alcoholism, glaucoma, chronic lung
disease, urinary retention, and heart block).

4. The participant has a known hypersensitivity to doxylamine succinate other
ethanolamine derivative antihistamines, pyridoxine hydrochloride, or any inactive
ingredient in the Diclegis or placebo formulation.

5. The participant is taking a monoamine oxidase inhibitor.

6. The participant has used antihistamines, anticholinergics, dopamine antagonists,
serotonin antagonists, ginger, or anti-emetic therapy (including acupressure,
acupuncture, homeopathic remedies, medical hypnosis, and relief bands) to treat NVP
in the previous 48 hours or plans to do so during the study.

7. The participant is using drugs that have anticholinergic activity (eg, tricyclic
antidepressants).

8. The participant is taking multivitamins containing more than 10 mg of vitamin B6 or
plans to do so during the study.

9. The participant is taking supplementary vitamin B6 in addition to any multivitamin
preparation or plans to do so during the study (e.g, total vitamin B6 greater than 10
mg).

10. The participant is currently drinking any amount of alcohol.

11. The participant has any condition that might interfere with the conduct of the study,
in the opinion of the investigator. For example, Diclegis® should be used with
caution in females with asthma, increased intraocular pressure, narrow angle
glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction and urinary bladder-neck
obstruction.

12. The participant is likely to be unable to comply with study procedures because of
inadequate cognitive or language skills.

13. The participant has received an investigational drug within 30 days before enrollment
in this study or is scheduled to receive an investigational drug during the course of
this study.

14. The participant is currently breastfeeding.