Safety, Tolerability, PD & PK of Calcipotriene 0.005% Foam, Under Maximal Use in 12-16 Year Olds With Plaque Psoriasis

This Phase 1 multicenter, open-label, repeat-dose study is designed to evaluate the safety,
tolerability, pharmacodynamics, and pharmacokinetics of calcipotriene foam, 0.005%, applied
topically to adolescent subjects with moderate plaque psoriasis (defined as a score of 3 on
the Investigator's Static Global Assessment [ISGA]) involving a minimum of 10% body surface
area (BSA) excluding the face and scalp, and a minimum of 20% scalp involvement. Subjects
will be enrolled no more than 2 weeks after Screening. Approximately 30 eligible subjects,
ages 12 to 16 years, inclusive, will be enrolled to ensure 20 completing subjects.
Calcipotriene foam will be applied as a thin layer twice a day for 14 days and once on Day 15
on all treatment areas. Blood samples for the evaluation of albumin adjusted calcium, intact
parathyroid hormone (iPTH), alkaline phosphatase, magnesium, and phosphorus will be taken at
Screening and on Day 1 (before the first dose), Day 15 (3 to 9 hours after dosing), and on
Day 22 if the results from Day 15 show any abnormalities. Serum 25-OH vitamin D
concentrations will be evaluated on Day 1 (before the first dose). Safety and tolerability
will be evaluated throughout the treatment period and a 7 day follow-up period. Blood samples
for pharmacokinetic (PK) evaluation will be collected on Days 1 and 15. Urine samples for
evaluation of calcium/creatinine ratio will be collected before dosing on Days 1 and 15.

Inclusion Criteria:

1. Male or female subjects, ages 12 to 16 years, inclusive, at the time of consent.

2. Plaque psoriasis involving 10% body surface area (excluding the scalp and face).

3. 20% scalp involvement (excluding the body and face).

4. Clinical diagnosis of mild to moderate plaque psoriasis, as defined by an ISGA score
at Screening of 3 on a scale of 0 to 4.

5. The ability and willingness of the subject and the subject's primary caregiver to
follow all study procedures, attend all scheduled visits, and successfully complete
the study.

5. The subject's parent(s) or legal guardian must have the ability to understand and sign a
written informed consent form and a Health Insurance Portability and Accountability Act
(HIPAA) authorization form, which must be obtained prior to participation in this study.
The HIPAA authorization may be incorporated in the informed consent form. Also, the
subject's assent must be obtained and documented.

Exclusion Criteria:

1. Any inflammatory skin disease in the treatment area that may confound the evaluation
of the plaque psoriasis (eg, atopic dermatitis, contact dermatitis, tinea corporis).

2. Current diagnosis of unstable forms of psoriasis in the treatment area, including
guttate, erythrodermic, exfoliative, or pustular psoriasis.

3. Use of any topical product (including sunscreen, creams, ointments, lotions, and
powders) applied on or near the treatment area within 48 hours prior to enrollment.

4. Use of topical treatments that have a known beneficial effect on psoriasis, including
but not limited to corticosteroids, retinoids, vitamin D derivatives, coal tar,
tazarotene, or anthralin, medicated shampoos within 2 weeks prior to enrollment.

5. Use of nonbiologic systemic antipsoriatic therapy (eg, corticosteroids, retinoids,
methotrexate, cyclosporine, other immunosuppressive agents), biologic therapy (eg,
alefacept, etanercept, efalizumab), or phototherapy (eg, ultraviolet A, psoralen and
ultraviolet A, ultraviolet B) within 4 weeks prior to enrollment.

6. Use or need for initiation of any nonpsoriatic therapy that might affect psoriasis
(including antimalarials, adrenergic receptor blockers, interferon, or lithium) within
4 weeks prior to enrollment.

7. Use of medications that affect or change calcium and parathyroid hormone (PTH)
concentrations or interfere with the measurement of calcium or PTH concentrations
within 4 weeks prior to enrollment.

8. Known difficult venous access beyond that expected for subject age.

9. Any serious skin disorder or any chronic medical condition that is not well
controlled.

10. Positive urine drug screen result for alcohol, cotinine, or drugs of abuse at the time
of Screening.

11. Average daily ingestion of more than 2000 mg of elemental calcium or more than 1000 IU
of vitamin D within 2 weeks prior to enrollment.

12. Current drug or alcohol abuse.

13. History of hypersensitivity, known allergy, or other adverse reaction to calcipotriene
or other vitamin D analogs or to any component of the study product.

14. Current or past history of hypercalcemia, vitamin D toxicity, severe renal
insufficiency, or severe hepatic disorders.

15. Use of any investigational therapy within 4 weeks prior to enrollment.

16. Pregnant, breastfeeding, or sexually active female subjects of childbearing potential
(after menarche) who are not practicing an acceptable method of contraception.
Acceptable methods of contraception include one of the following highly effective
methods of contraception (ie, Pearl Index <1.0%): complete abstinence from intercourse
or 2 forms of barrier contraception (diaphragm plus spermicide for females, condom
plus spermicide for males), or systemic contraceptives (combined or progesterone only)
used in combination with a condom. The subject must agree to use an acceptable method
of contraception from 2 weeks prior to administration of study product, throughout the
study, and for 28 days after completion or premature discontinuation from the study.

17. Current immunosuppression.

18. Albumin-adjusted serum calcium at Screening that is outside the normal reference
range.

19. Any other condition that, in the judgment of the investigator, would put the subject
at unacceptable risk for participation in the study.