Clinical trial NCT01165281: A Safety and Efficacy Study of JNS024 Extended Release (ER) in Japanese and Korean Patients With Chronic Malignant Tumor-Related Cancer Pain
Official title: A Randomized, Double-Blind, Active Controlled, Optimal Dose Titration, Multicenter Study to Evaluate the Safety and Efficacy of Oral JNS024 Extended Release (ER) in Japanese and Korean Subjects With Moderate to Severe Chronic Malignant Tumor Related Cancer Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain
Keywords: Pain
R331333 (JNS024ER, CG5503), tapentadol (NUCYNTA)
Opioid analgesic
Oxycodone CR (OXYCONTIN CR)
Chronic malignant tumor related cancer pain
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2010-07-19
Enrollment: 343
Sex: ALL
Minimum age (years): 20
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of R331333 (referred to as JNS024 Extended-Release (ER) or CG5503) compared with an active comparator (oxycodone Controlled Release (CR)) in Japanese and Korean patients with chronic, malignant, tumor-related cancer pain.

Detailed description: This is a randomized (study drug assigned by chance), double-blind (neither the patient nor the study staff will know the identity of the study drug assigned to each patient), multicenter study to evaluate the safety and efficacy of orally (by mouth) administered R331333 (referred to as JNS024 extended release \[ER\] capsules or CG5503) in dosages of 25 mg to 200 mg twice daily compared with orally administered capsules of oxycodone controlled release (CR) in dosages of 5 mg to 40 mg twice daily over 4 weeks in Japanese and Korean patients with moderate to severe chronic malignant tumor-related cancer pain who require around-the-clock opioid therapy (treatment with narcotic analgesics or pain relievers) and are dissatisfied with the pain relief they are experiencing from current treatment. The active control, oxycodone CR, is being used in this study because it is an opioid analgesic approved for the treatment of moderate to severe pain. Approximately 212 Japanese patients and approximately 100 Korean patients who meet screening criteria for the study will be enrolled in the study and will enter the titration period of the study where they will receive a starting dosage of either JNS024 ER 25 mg twice daily or oxycodone CR 5 mg twice daily. The dose of study drug for each patient will be titrated (increased) to the optimal dose until sufficient analgesia (pain relief) is achieved (ie, up to a maximum dose of JNS024 ER 200 mg twice daily or Oxycodone CR 40 mg twice daily). When the dosage of study drug is increased, the safety will be confirmed at the study visit or by telephone on the day after the dose is increased. Once an optimal dose of study drug is determined, the patient will continue to receive that dose during the maintenance period in the study. Patients will participate in the study for total of approximately 6 weeks; during this time patients will receive study drug for 4 weeks (titration and maintenance periods combined). During the study, if a patient experiences breakthrough pain (pain that occurs for short periods of time between doses of study drug), treatment with rescue medication (morphine immediate release \[IR\] 5 mg) will be given. In addition, patients will be allowed to continue to take stable doses of non-opioid analgesics (non-narcotic pain medications for mild to moderate pain) that they were taking at the time of study entry and may reduce the dosage or discontinue their use during the study. During the study, blood samples will be collected from patients at protocol-specified time points to determine the concentration of study drug after administration. The safety of patients will be monitored during the study by evaluating adverse events and findings from clinical laboratory tests, physical examinations, vital signs measurements, and electrocardiogram (ECG) measurements reported. The primary outcome measure in the study will be the change from baseline to the last 3 days of study drug administration in the average pain intensity score using an 11 point numerical rating scale (NRS). Patients will receive R331333 (referred to as JNS024 ER or CG5503) by mouth with or without food at a starting dose of 25 mg twice daily to be increased if necessary to a maximum dose of 200 mg twice daily for a total of 4 weeks (titration and maintenance periods combined) OR double-blind oxycodone CR by mouth with or without food at a starting dose of 5 mg twice daily to be increased if necessary to a maximum dose of 40 mg twice daily for a total of 4 weeks.

Eligibility criteria: Inclusion Criteria:

* Documented clinical diagnosis of any type of cancer
* Diagnosis of chronic malignant tumor-related cancer pain with an average score for pain intensity in the past 24 hours of \>=4 on the 11-point numerical rating scale (NRS) on the day of randomization (Day -1)
* Have not received treatment with opioid analgesics within 28 days before screening (Note: codeine phosphate \[\<=60 mg/d\] or dihydrocodeine phosphate \[\<=30 mg/d\] for antitussive use are allowed)
* Dissatisfied with pain relief by the current treatment and for whom the investigator or designee judges that treatment with opioid analgesics is required

Exclusion Criteria:

* Have complicated with uncontrolled/clinically significant arrhythmia
* Have previous or concurrent presence of any disease which may develop increased intracranial pressure, disturbance of consciousness, lethargy, or respiratory problems such as traumatic encephalopathy with cerebral contusion, intracranial hematoma, disturbance of consciousness, brain tumor, cerebral infarction, transient ischemic attack, epilepsy or convulsive diseases
* Have history of alcohol and/or drug abuse
* Have any disease for which opioids are contraindicated such as serious respiratory depression of serious chronic obstructive pulmonary disease, bronchial asthma attack, cardiac failure secondary to chronic pulmonary disease, paralytic ileus, status epileptics, tetanus, strychnine poisoning, acute alcohol poisoning, hypersensitivity to opium alkaloid, hemorrhagic colitis, or bacterial diarrhea

Primary outcomes:
measure: Change From Baseline to the Last 3 Days of Study Drug Administration (Last Observation Carried Forward) in the Score for Average Pain Intensity on an 11-point Numerical Rating Scale
timeFrame: Baseline, Last 3 Days of Study Drug Administration (4 weeks)
Secondary outcomes:
measure: Percentage of Patients in Patient Global Impression of Change (PGIC) Score Categories
timeFrame: Baseline, Endpoint of the 4-week Treatment Period
measure: Frequency of Rescue Medication Use for the Double-blind Treatment Period
timeFrame: 4 weeks
measure: Total Daily Dose of Rescue Medication Use for the Double-blind Treatment Period
timeFrame: 4 weeks
measure: Proportion of Patients With Various Levels of Pain Improvement (Responders)
timeFrame: Baseline, Last 3 Days of Study Drug Administration (4 weeks)
measure: Proportion of Patients Entering the Maintenance Period
timeFrame: 4 weeks
measure: Number of Patients Who Discontinued Due to Lack of Efficacy
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Chiba
country: Japan
city: Fukui
country: Japan
city: Fukushima
country: Japan
city: Fukuyama
country: Japan
city: Fushimi
country: Japan
city: Hamamatsu
country: Japan
city: Hirosaki
country: Japan
city: Hitachi
country: Japan
city: Itami
country: Japan
city: Iwakuni
country: Japan
city: Izumo
country: Japan
city: Kamogawa
country: Japan
city: Kanuma
country: Japan
city: Kobe
country: Japan
city: Kumagaya
country: Japan
city: Kumamoto
country: Japan
city: Kure
country: Japan
city: Kyoto
country: Japan
city: Matsumoto
country: Japan
city: Matsusaka
country: Japan
city: Miyazaki
country: Japan
city: Nagoya
country: Japan
city: Natori
country: Japan
city: Niigata
country: Japan
city: Ogori
country: Japan
city: Ohta
country: Japan
city: Okayama
country: Japan
city: Osaka
country: Japan
city: Saga
country: Japan
city: Saku
country: Japan
city: Sapporo
country: Japan
city: Sendai
country: Japan
city: Sunto
country: Japan
city: Takarazuka
country: Japan
city: Takasaki
country: Japan
city: Tokyo
country: Japan
city: Tomakomai
country: Japan
city: Toyama
country: Japan
city: Toyonaka
country: Japan
city: Ube
country: Japan
city: Yamagata
country: Japan
city: Yamanashi
country: Japan
city: Yokohama
country: Japan
city: Busan
country: Korea, Republic of
city: Chungcheongbuk-Do
country: Korea, Republic of
city: Dae-Gu
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Deajun
country: Korea, Republic of
city: Gyeonggi-Do
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Jinju-Si
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Imanaka K, Tominaga Y, Etropolski M, van Hove I, Ohsaka M, Wanibe M, Hirose K, Matsumura T. Efficacy and safety of oral tapentadol extended release in Japanese and Korean patients with moderate to severe, chronic malignant tumor-related pain. Curr Med Res Opin. 2013 Oct;29(10):1399-409. doi: 10.1185/03007995.2013.831816. Epub 2013 Aug 23.