A Safety and Efficacy Study of Oral Tapentadol Extended-Release in Japanese Participants

Phase 3

Completed

Conditions: Neoplasms

Interventions: Drug: Tapentadol ER
Drug: Morphine SR

Registration Number: NCT01309386

Lead Sponsor: Janssen Pharmaceutical K.K.

Brief Summary: The purpose of this study is to evaluate the conversion rate based on the number of participants achieving pain control and safety within 1 week after switching the opioid (morphine-like medications) analgesics (drug used to control pain), when tapentadol extended-release (ER) (JNS024ER) is orally administered to participants treated with around-the-clock opioid analgesics, for their moderate to severe (very serious, life threatening) chronic (lasting a long time) malignant (cancerous) tumor-related (a mass in a specific area) cancer (abnormal tissue that grows and spreads in the body) pain.

Detailed Description: This is a randomized (study drug assigned by chance), open-label (a medical research study in which participants and researchers are told which treatments the participants are receiving, "unblinded"), parallel-arm (participants receive 1 of 2 possible interventions during the same time frame throughout the study), optimal dose-titration, multicenter (when more than one hospital or medical school team work on a medical research study) study evaluating the conversion rate based on the number of participants achieving pain control and safety within 1 week after switching from an ongoing around-the-clock opioid analgesic (morphine sustained-release \[SR\], oxycodone controlled-release, or fentanyl transdermal) to tapentadol ER or morphine SR, for their moderate to severe chronic, malignant tumor-related cancer pain. The study consists of 2 periods: 1 to 2 week screening period, followed by 8-week open-label treatment period. During the study period, participants will be hospitalized or outpatient. However, it is preferable to be hospitalized 1 week before and 1 week after to evaluate efficacy before and after switching opioids for securing participants' safety. At Day 1, participants will receive either tapentadol ER or morphine SR twice daily. During the treatment period, the dose of the study drug will be titrated to the participant's optimal dose. The participants will receive either tapentadol ER or morphine SR twice daily for 8 weeks. The maximum dose allowed for tapentadol ER will be 500 milligram (mg) daily or morphine SR 140 mg daily throughout the study. Efficacy is primarily evaluated using pain intensity score on an 11 point Numerical Rating Scale (an 11-point NRS is used to measure the pain level where 0=no pain to 10=pain as bad as you can imagine). Participants' safety will also be monitored.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 100

Inclusion Criteria

Participants with documented clinical diagnosis (determination of the cause of a medical problem) of any type of cancer (abnormal tissue that grows and spreads in the body)
Participants with mean 24-hour Numerical Rating Scale (NRS) score (11-point NRS used to measure the pain level for the past 24-hours where 0=no pain to 10=pain as bad as you can imagine) during 3 days (Day -4 to Day -2) before randomization (study drug assigned by chance) less than 4.0
Women must be post-menopausal, surgically sterile, or before entry and throughout the study practicing an effective method of birth control
Participants using immediate-release (IR) morphine hydrochloride (HCl) or oxycodone HCl hydrate as rescue medication (rescue medications are medicines that may be administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation) for breakthrough pain
Participants treated with around-the-clock opioid (morphine-like medications) therapy for moderate to severe (very serious, life threatening) chronic (lasting a long time), malignant (cancerous) tumor-related (a mass in a specific area) cancer (abnormal tissue that grows and spreads in the body) pain using one of the following opioid analgesics (drug used to control pain) before randomization: morphine SR tablet less than or equal to 120 milligram (mg) per day, oxycodone hydrochloride controlled release (CR) tablet: 15 mg to 80 mg per day, durotep MT (fentanyl transdermal [through the skin] matrix) patch less than or equal to 8.4 mg per patch, fentos tape less than or equal to 4 mg per tape, or oneduro patch less than or equal to 3.4 mg per patch

Exclusion Criteria

Participants with complicated uncontrolled/clinically significant arrhythmia (uneven heart beat)
Participants who had received rescue doses 3 times or more daily within 3 days (Day -4 to Day -2) before the randomization
History of surgery intended for the cure of the primary disease or for the treatment of cancer pain within 28 days before screening
Participants who had application of radiotherapy (treatment of cancer using x-rays), nerve block, or stimulation analgesia within 7 days before screening
Participants with known allergies (over sensitivity to a substance), hypersensitivity, or intolerance to opioid analgesics or its excipients

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tapentadol ER	Tapentadol ER	Tapentadol extended-release (ER) (JNS024ER) oral tablets 100 to 400 milligram (mg) daily for 8 weeks (maximum dose could be up to 500 mg daily), as per Investigator's discretion.
Morphine SR	Morphine SR	Morphine sustained-release (SR) oral tablets 30 to 120 mg daily for 8 weeks (maximum dose could be up to 140 mg daily), as per Investigator's discretion.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Pain Control	Week 1	Pain control was considered to be achieved for participants who met both of the following criteria for any consecutive 3 days during the first week of treatment period: a) Change from baseline of mean 24 hour numerical rating scale (NRS) (an 11-point NRS is used to measure the pain level where 0=no pain to 10=pain as bad as you can imagine) score less than +1.5, and b) when the frequency of rescue medication was twice or less per day.

Secondary Outcome Measures

Name	Time	Method
Average Change From Baseline in Amount of Rescue Medication Over Time	Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8	Rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. Supplemental analgesics (drug used to control pain) were used as rescue medication. Average amount was the averages of all doses recorded during the baseline period or during each week (Week 1, 2, 3, 4, 5, 6, 7 and 8).
Change From Baseline in Numerical Rating Scale (NRS) at Week 1, 2, 3, 4, 5, 6, 7 and 8	Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8	Average pain intensity was assessed using an 11-point NRS to measure the pain level for the past 24-hours where 0=no pain to 10=pain as bad as you can imagine.
Number of Participants Who Discontinued Study Treatment Due to Lack of Efficacy	Baseline up to Week 8	Number of participants who discontinued the treatment due to lack of efficacy were assessed throughout the study.
Number of Participants With Patient Global Impression of Change (PGIC)	Week 1, 4 and 8	The PGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved".
Total Number of Days of Rescue Medication Over Time	Baseline up to Week 8	Total number of days of rescue medication over time were assessed. Rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. Supplemental analgesics (drug used to control pain) were used as rescue medication.
Number of Doses of Rescue Medication Over Time	Baseline up to Week 8	Number of doses of rescue medication over time were assessed. Rescue medications are medicines that are administered to the participants when the efficacy of the study drug is not satisfactory, or the effect of the study drug is too great and is likely to cause a hazard to the participant, or to manage an emergency situation. Supplemental analgesics (drug used to control pain) were used as rescue medication.