Efficacy/Safety Study of ACTIQ® for Opioid-Tolerant Children and Adolescents With Breakthrough Pain (BTP)

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00236041
• Other study ID #: C8278b/202/BP/US-CA
• Status: Completed
• Phase: Phase 2
• First received: October 7, 2005
• Last updated: May 8, 2014
• Start date: April 2004
• Est. completion date: August 2006

Study information

• Verified date: May 2014
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to evaluate the efficacy of ACTIQ treatment for the management of breakthrough pain (BTP) compared to placebo treatment in children with cancer and non-cancer pain who are receiving around-the-clock (ATC) opioid therapy and who require additional therapy for BTP episodes. This will be determined by the analysis of the pain intensity (PI), measured by the Faces Pain Scale-Revised (FPS-R) administered 15 minutes after the start of each unit of study drug with an optimal ACTIQ dosage.

Description:

The primary objective of the study is to evaluate the efficacy of ACTIQ treatment for the management of breakthrough pain (BTP) compared to placebo treatment in children with pain who are receiving around-the-clock (ATC) opioid therapy and who require additional therapy for BTP episodes. This will be determined by the analysis of the pain intensity (PI), measured by the Faces Pain Scale-Revised (FPS-R) administered 15 minutes after the start of each unit of study drug with an optimal ACTIQ dosage.

The secondary objectives are:

• to evaluate the characteristics of BTP in children with pain, including their response to treatment

• to evaluate the efficacy of ACTIQ treatment compared to placebo treatment for these children with regard to time to adequate analgesia by utilizing a stop watch to measure the time for each unit of study drug in the double blind phase

• to evaluate the efficacy of ACTIQ treatment compared to placebo treatment for these children by assessing the occurrence of inadequate analgesia as assessed by the use of rescue medication

• to evaluate the efficacy of ACTIQ treatment compared to placebo treatment for these children by assessing the numbers of patients who withdraw from the study because of inadequate analgesia

• to evaluate the efficacy of ACTIQ treatment compared to placebo treatment for these children by assessing the duration of analgesic effect by using the FPS-R administered at approximately 30, 45, and 60 minutes after the start of each unit of study drug after an optimal dosage is obtained

• to determine the distribution of optimal doses of ACTIQ treatment for these children by age group (3 to under 6 years, 6 to under 11 years, and 11 to under 16 years)

• to establish a safe and effective titration scheme for ACTIQ in these children during the open label phase

• to evaluate the safety of ACTIQ treatment for these children through the assessment of adverse events, clinical laboratory assessments (serum chemistry and hematology), vital sign measurements (including blood pressure, heart rate, and respiration rate), hemoglobin-oxygen saturation level (SpO2, measured via pulse oximetry), electrocardiograms (ECGs), physical examinations, and level of sedation (measured by the University of Michigan Sedation Scale [UMSS])

• to characterize the pharmacokinetics profile of ACTIQ (fentanyl citrate) in these children

• to investigate the exposure and efficacy relationship between plasma concentration of fentanyl and clinical measures of analgesia

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 15 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breakthrough Pain
• Cancer

Intervention

Drug:
• ACTIQ®

Locations

Country	Name	City	State
Puerto Rico	San Jorge Childrens Medical	San Juan
United States	Akron Children's Hospital	Akron	Ohio
United States	University of New Mexico	Albuquerque	New Mexico
United States	Scottish Rite Children's Medical Center	Atlanta	Georgia
United States	Children's Hospital at Montefiore	Bronx	New York
United States	Children's Memorial Center	Chicago	Illinois
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Duke University Hospital	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Childrens Medical Center	Hartford	Connecticut
United States	Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Kapi'olani Medical Center	Honolulu	Hawaii
United States	University Hospitals of Iowa	Iowa City	Iowa
United States	Nemours Childrens Clinic	Jacksonville	Florida
United States	Children's Hospital of Arkansas	Little Rock	Arkansas
United States	UCLA Pediatric Pain Program	Los Angeles	California
United States	Childrens Hospital of Wisconsin	Milwaukee	Wisconsin
United States	West Virginia University	Morgantown	West Virginia
United States	Vanderbilt University Medical	Nashville	Tennessee
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Childrens Hospital of Orange	Orange	California
United States	Lucille Packard Childrens Hospital	Palo Alto	California
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Children's Cancer and Blood Disorders Center	San Antonio	Texas
United States	Methodist Hospital	San Antonio	Texas
United States	Sacred Heart Medical Center	Spokane	Washington
United States	Cardinal Glennon Children's Hospital	St. Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York
United States	St. Joseph's Children's Hospital	Tampa	Florida
United States	Children's National Medical Center	Washington	District of Columbia
United States	Tod Children's Hospital	Youngstown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Cephalon

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain intensity differences as measured by the FPS-R
Secondary	Time to adequate analgesia
Secondary	Duration of analgesia
Secondary	Percentage of BTP episodes requiring rescue medication, or for which oversedation occurs
Secondary	Amount of rescue medication
Secondary	Distribution of optimal doses