A Double-Blind, Placebo-Comparison Study to Evaluate the Efficacy and Safety of ACTIQ® (Oral Transmucosal Fentanyl Citrate [OTFC®]) Treatment for Opioid-Tolerant Children and Adolescents With Breakthrough Pain

Inclusion Criteria:

1. Written informed consent of the parent or legal guardian and patient assent, when
appropriate, is obtained. (Lack of assent cannot be overturned.)

2. The child is aged 3 to under 16 years and weighs at least 15 kg.

3. The child must be using ATC opioid therapy for pain associated with cancer and be
opioid-tolerant. NOTE: This requirement is defined as the patient receiving at least
1 mg/kg/day or 40 mg/day or more of oral morphine (or an equi-analgesic dosage of
another opioid) or at least 25 mcg/hour of transdermal fentanyl for at least 7 days,
(ATC opioid therapy may be administered as patient-controlled analgesia [PCA]).

4. The child must be experiencing episodes of BTP (defined as a transient flare of pain
that requires a bolus of medication as treatment) as follows:

1. patients with cancer must be experiencing an average of at least 1 BTP episode a
day.

2. patients with non-cancer related pain must be experiencing an average of 2 BTP
episodes a day.

5. The child has an average daily pain score of 6 or less (of 10) on the FPS-R.

6. Girls who are postmenarche or sexually active must have a negative urine pregnancy
test prior to the baseline visit, must be using a medically acceptable method of
birth control, and must agree to continue use of this method for the duration of the
study (and for 30 days after participation in the study). Acceptable methods of birth
control include: barrier method with spermicide; steroidal contraceptive (eg, oral,
transdermal, implanted, or injected) in conjunction with a barrier method;
intrauterine device (IUD); or abstinence.

7. The child, in the opinion of the investigator, is able to administer ACTIQ treatment
effectively (ie, adequately moving the unit around in the mouth and sucking, not
biting, the unit).

8. The child must be an inpatient.

Exclusion Criteria:

1. The child has pain uncontrolled by therapy, as determined by the investigator, that
could adversely impact the safety of the patient or could be compromised by treatment
with ACTIQ.

2. The child has known or suspected hypersensitivities/allergies or other
contraindications to any ACTIQ component.

3. The child has received monoamine oxidase inhibitors (MAOIs) within 14 days before the
first ACTIQ treatment.

4. The child has moderate to severe oral mucositis.

5. The child has a neuromuscular disease, significant renal impairment, or significant
hepatic impairment as determined by the investigator.

6. The child has any other medical condition or is receiving concomitant
medication/therapy that would, in the opinion of the investigator, compromise the
patient’s safety or compliance with the study protocol, or compromise data
collection.

7. The child has received any experimental drug/therapy within 14 days of the first
ACTIQ treatment. NOTE: Children may not be participating concurrently in another
study when the other study requires experimental drug therapy.

8. A child's exacerbations of pain are only associated with medical procedures (such as
radiation therapy, wound dressing, and bone marrow aspiration).

9. The child is receiving any other treatment that, in the opinion of the investigator,
could interfere with the pain response.

10. For a female patient of childbearing potential: is pregnant or lactating. (Any female
patient becoming pregnant during the study will be withdrawn from the study.)

11. The child has, in the opinion of the investigator, developmental delay that would
interfere with the use of ACTIQ therapy.