Recombinant Human Prolactin for Lactation Induction

The efficacy of recombinant human prolactin (r-hPRL) for treatment of primary lactation
insufficiency in women with prolactin deficiency, either congenital or acquired, will be
examined. Subjects will participate in an open-label study of r-hPRL administration for
prolactin deficiency. On study day 1, subjects will be seen between 8 and 10 am. A baseline
prolactin level will be obtained. Subjects will subsequently be taught to use a breast pump
by a designated lactation consultant and will pump for 10 minutes at each breast,
simultaneously or sequentially. Any milk production will be recorded, along with milk volume
throughout the study. Prolactin levels will be obtained every 10 minutes for 60 minutes after
pumping begins, then every 30 minutes for a total of 3 hours. At 3 hours, r-hPRL 60 mg/kg
will be administered SC. Blood will be drawn every 2 hours for 8 hours to obtain a peak
prolactin level. Vital signs will be monitored every 15 minutes for the first hour, then
every 2 hours for a total of 8 hours. Subjects will again pump both breasts 0, 3 and 6 hours
after the r-hPRL injection, to maintain an every 3 hour schedule. Any milk production will be
recorded. Subjects will administer their second dose of SC r-hPRL 12 hours after the first
dose.

Subjects will continue every 12 hour SC r-hPRL administration for the next 28 days. They will
also pump every 3 hours, with the exception of a 5 hour break for sleep at one time during
the 24 hours, as long as the total number of pumping episodes equals 8. Subjects will record
any milk production and will call as soon as any milk is expressed. When the first milk is
produced, the infant will not be allowed to suckle at the breast until the milk is tested and
readministered to the infant in a controlled setting to avoid any potential risks or r-hPRL
exposure to the infant in the interim. After each pumping episode, if no milk is produced
mothers will be encouraged to let their infants feed at the breast using a Lact-Aid device.

Subjects will be seen in the GCRC, weekly for 28 days. At each visit, subjects will have a
breast exam for galactorrhea and a baseline prolactin level, then subjects will administer
their own SC r-hPRL injection and pump at 0, 3 and 6 hours after r-hPRL administration, as
described above. Any milk production will be recorded. In addition, at the end of week 1 and
on the final day, r-hPRL will be administered, blood will be drawn every 2 hours for
prolactin levels as on the first day of the injection, for a total of 8 hours, and subjects
will pump and milk volume will be recorded at 0, 3 and 6 hours after r-hPRL administration.

When at least 0.25 cc of milk is produced by pumping, it will be sent for a prolactin level
measurement to determine whether levels are elevated compared to levels in the control milk.
If the prolactin level is not elevated, milk will be readministered to the infant. When
breast milk is first given to the infants, they will be monitored in the GCRC under the
supervision of a neonatologist, with vital signs, including temperature, measured every hour
after feeding for 4 hours. The mother will also record stool and gastric output and any
changes noted in the quality or quantity of output for the following 24 hours. If any
significant and adverse changes in vital signs or gastric output are observed, any additional
stored breast milk will be discarded and the study stopped. After the prolactin level in milk
has been documented in the normal range and milk readministered to the infant under
supervision in the GCRC, mothers will continue to pump immediately after the am r-hPRL dose,
but at all other times will be encouraged to breastfeed.

When at least 1 cc of milk is available, milk composition will also be analyzed for fat,
protein, glucose, lactose and IgA levels (see Procedure for Analyzing Collected Milk, above).
Studies in mothers of premature infants will be performed before starting this protocol. If
the level of any of these components is 50% below the lower limit of normal, breast milk will
be supplemented with formula at a ratio determined by the neonatologist to ensure that all
nutrients are received.

After completing 28 days of every 12 hour r-hPRL administration, breast milk production will
continue to be monitored for a 14 day control period. Subjects will be seen at 7 and 14 days
after their final prolactin injection. After a baseline prolactin level is drawn, milk will
be pumped until the breasts are emptied. Blood will be drawn at baseline and then every 10
minutes for 60 minutes, then every 30 minutes for a total of 3 hours to obtain a prolactin
peak.

Inclusion Criteria:

- Healthy women, aged 18-45 years

- Prolactin deficiency due to congenital deficiency, surgery or radiation, or Sheehan's
syndrome during the current or previous pregnancies, for women who desire to
breastfeed their infants.

- Postpartum at the time of study participation

- Milk must fail to come in by 2-4 days after delivery.

- Prolactin levels will be less than the lower limit of normal for the assay performed.
If a subject is postpartum, prolactin levels will be less than the normal range for
postpartum women (<= 138.0 ± 11.9 ng/mL).

- Free T4 index must be normal either on or off thyroid hormone replacement.

- Fasting am cortisol or 1 hour Cortrosyn 0.25 mg stimulated cortisol must be normal
(>18 mg/dL). If it is not normal, subjects must be on glucocorticoid replacement and
have no symptoms of adrenal insufficiency.

- History of normal spontaneous puberty or Tanner stage V breast development after
previous estrogen replacement therapy.

Exclusion Criteria:

- Current use of medications known to increase or decrease prolactin

- Anatomical breast abnormalities

- Previous mammoplasty

- Breast augmentation

- Current use of hormonal contraception

- Allergies to mannitol

- Medications contraindicated for breastfeeding mothers