Cancer, Pain
Conditions
Keywords
EN3267, Breakthrough Pain, Safety Study, Fentanyl Tablets
Brief summary
The purpose of this study is to evaluate the long-term safety and effectiveness of EN3267 in treating breakthrough pain episodes in opioid cancer patients who are using stable doses of opioid medication.
Detailed description
This was a Phase 3 non-randomized, open-label, multicentre study designed to evaluate the long-term safety of EN3267 in the treatment of BTcP in opioid-tolerant cancer patients. The study was conducted in 2 parts: 1. A Titration Period during which patients had up to 2 weeks to determine a single, effective dose of study medication (EN3267) for adequate treatment of BTcP, and 2. A maintenance Period of up to 12 months in which episodes of BTcP were treated with study medication.
Interventions
DRUGEN3267
EN3267 will be available in 100, 200, 300, 400, 600 (two 300 ug tablets), and 800 ug (two 400 ug tablets) doses
Sponsors
Kyowa Kirin Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or females 17 years of age or older. * Stable cancer-related pain. * Are receiving a stable, fixed-schedule oral opioid regimen equivalent to 60 to 1000 mg of oral morphine per day or transdermal fentanyl therapy equivalent to 50 to 300 µg/h, and are on a stable dose of opioid medication for relief of breakthrough pain. * Experiencing 1-4 episodes of breakthrough pain per day. * Meet the criteria defined in the Eastern Cooperative Oncology Group (ECOG) Performance Status for Grade 0, 1, or 2.
Exclusion criteria
* Have previously been exposed to EN3267. * Are pregnant or lactating. * Have uncontrolled or rapidly escalating pain. * Have any clinically significant condition that would, in the investigator's opinion, preclude participation in the study or compromise data collection. These conditions may include cardiopulmonary disease, and/or neurologic/psychologic conditions. * Are scheduled to take MAOIs (monoamine oxidase inhibitors) during the study. * Are scheduled to receive anti-neoplastic therapy that, in the investigator's opinion, will influence assessment of breakthrough pain. * Are scheduled to receive an investigational drug other than EN3267 during the course of the study. * Have hypersensitivity, allergy or contraindication to fentanyl. * Have significant prior history of substance abuse or alcohol abuse. * Would have difficulty complying with the protocol, as assessed by the investigator. * Are unable to read, write, or comprehend the English language in order to complete diaries.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluate the Long-term Safety and Effectiveness of EN3267 | screening, 2 week titration period and 12 monthly study visits |
Countries
United States
Participant flow
Recruitment details
Recruitment period was first patient screened in December 2005 to last patient screened in November 2008. Patients were recruited from Medical Institutions in the US.
Pre-assignment details
Patients with stable cancer-related pain receiving stable, fixed-schedule oral opioid regimen. Patients were not permitted to have 2 consecutive days without at least 1 episode of BTcP. This regimen was for 14 days prior to screening and was expected to remain unchanged for the titration period. Patients with ulcerative mucositis were permitted.
Participants by arm
| Arm | Count |
|---|---|
| Sublingual Fentanyl Tablet EN3267 : EN3267 will be available in 100, 200, 300, 400, 600 (two 300 ug tablets), and 800 ug (two 400 ug tablets) doses | 139 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Maintence Period | Adverse Event | 23 |
| Maintence Period | Lack of Efficacy | 4 |
| Maintence Period | Lost to Follow-up | 1 |
| Maintence Period | Other | 7 |
| Maintence Period | Physician Decision | 6 |
| Maintence Period | Protocol Violation | 4 |
| Maintence Period | Sponsor Decision | 24 |
| Maintence Period | Withdrawal by Subject | 8 |
| Titration Period | Adverse Event | 14 |
| Titration Period | Lack of Efficacy | 6 |
| Titration Period | Other | 2 |
| Titration Period | Protocol Violation | 9 |
| Titration Period | Sponsor Decision | 2 |
| Titration Period | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | Sublingual Fentanyl Tablet |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 33 Participants |
| Age, Categorical Between 18 and 65 years | 106 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 11.6 |
| Region of Enrollment United States | 139 participants |
| Sex: Female, Male Female | 76 Participants |
| Sex: Female, Male Male | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 116 / 139 |
| serious Total, serious adverse events | 46 / 139 |
Outcome results
Primary
Evaluate the Long-term Safety and Effectiveness of EN3267
Time frame: screening, 2 week titration period and 12 monthly study visits
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Titration | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with at least 1 SAE | 7 participants |
| Titration | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with an AE resulting in death | 4 participants |
| Titration | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with at least 1 AE | 64 participants |
| Titration | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with at least 1 AE causing discontinue | 14 participants |
| Maintenance | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with at least 1 SAE | 40 participants |
| Maintenance | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with at least 1 AE | 87 participants |
| Maintenance | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with at least 1 AE causing discontinue | 23 participants |
| Maintenance | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with an AE resulting in death | 15 participants |
| Overall | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with at least 1 AE causing discontinue | 37 participants |
| Overall | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with an AE resulting in death | 19 participants |
| Overall | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with at least 1 AE | 116 participants |
| Overall | Evaluate the Long-term Safety and Effectiveness of EN3267 | Patients with at least 1 SAE | 46 participants |