A Phase 2 Study of Tapentadol Extended-Release (JNS024ER) ) in Japanese Participants With Chronic Pain Due to Diabetic Neuropathic Pain or Postherpetic Neuralgia

• Sponsor: Janssen Pharmaceutical K.K. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01124617
• Collaborator: (none)
• Enrollment: 91
• Locations: 32
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the efficacy and safety of tapentadol extended-release (ER) tablets in Japanese participants with moderate to severe chronic (lasting a long time) pain due to painful diabetic peripheral neuropathy (pain in the extremities related to diabetes-induced nerve damage) or postherpetic neuralgia (pain lasting after condition has healed).

Condition or Disease	Intervention/Treatment	Phase
Pain; Diabetic Neuropathies; Neuralgia; Postherpetic Neuralgia	Drug: Tapentadol; Drug: Placebo	Phase 2

Detailed Description

This is a randomized (study drug assigned by chance), multi-center (when more than one hospital or medical school team works on a medical research study), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-control (participants are randomly assigned to a test treatment or to an identical-appearing treatment that does not contain the test drug), and parallel-group (each group of participant will be treated at the same time) comparison study in Japanese participants with chronic pain due to painful diabetic peripheral neuropathy or postherpetic neuralgia. The duration of study will be 14 weeks. The study consists of 3 parts: Screening (1 Week before study commences on Day 1); Treatment (12 weeks and will include titration period [from the initiation of the study treatment to determination of the individual's maintenance dose] and maintenance period [from completion of the titration period up to12 week]); and Follow-up (1 Week). Tapentadol hydrochloride ER oral tablet or matching placebo will be administered twice daily for 12 weeks. Efficacy of the participants will primarily be evaluated through Numerical Rating Scale (NRS). Participants' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase II Study of JNS024ER in Japanese Subjects With Chronic Pain Due to Diabetic Neuropathic Pain or Postherpetic Neuralgia
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tapentadol Tapentadol hydrochloride extended-release(ER) will be administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Drug: Tapentadol; Tapentadol hydrochloride extended-release(ER) will be administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.; Other Names: JNS024ER
Placebo Comparator: Placebo Matching Placebo will be administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.	Drug: Placebo; Matching Placebo will be administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Average Numerical Rating Scale (NRS) Score at Week 12 [Baseline and Week 12]

   Participants were asked to assess the average pain intensity on an 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number on the scale applicable to their pain. Baseline pain score is defined as the average pain intensity score over the last 3 days prior to the randomization. Change from Baseline in NRS score is the mean NRS score at Week 12 minus mean NRS score at Baseline.

Secondary Outcome Measures

1. Change From Baseline in Average Numerical Rating Scale (NRS) Score at Week 1 to 11 [Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11]

   Participants were asked to assess the average pain intensity on an 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number on the scale applicable to their pain. Baseline pain score is defined as the average pain intensity score over the last 3 days prior to the randomization. Change from Baseline in NRS score is the mean NRS score at corresponding week minus mean NRS score at Baseline.

2. Percentage of Participants With Treatment Response Based on Numerical Rating Scale (NRS) [Week 12]

   Percentage of participants with treatment response in mean NRS score by greater than equal to 30 or 50 percent (%) in the last week from baseline were considered as responders. Participants were asked to assess the average pain intensity on an 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number applicable to their pain on the scale.

3. Number of Participants With Categorical Scores on Patient's Global Impression of Change (PGIC) Scale [Week 8 and Week 12]

   The PGIC is a 7-point scale that requires the participants to assess how much their illness has improved or worsened relative to a Baseline state at the beginning of the intervention. The response options are 1 = very much improved, 2 = much improved, 3 = minimally improve, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.

4. Number of Participants With Categorical Scores on Physician's Global Assessment Scale [Week 8 and Week 12]

   Physician's Global Assessment Scale assesses the therapeutic efficacy (effectiveness) of the study drug for pain control on a 2-point scale of "effective" and "ineffective".

5. Change From Baseline in Pain Interference Subscale Score Based on Brief Pain Inventory (Short Form) (BPI-sf) Scale [Baseline and Week 12]

   The BPI-sf consists of 15 Items (Item 1:presence of pain; Item 2:pain location; Items 3 to 6:pain severity; Item 7:status of pain treatment; Item 8:efficacy of pain treatment; and Items 9a to 9g: interference of pain with daily life). Pain interference sub-scale score ranges from 0 (do not interfere) to 10 (completely interferes). Higher scores indicates worsening. Total score is defined as the mean scores from Items 3, 4, 5, 6 and 9 recorded on an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. Lower score indicates an improvement in pain.

6. Change From Baseline in Pain Subscale Score Based on Brief Pain Inventory (Short Form) (BPI-sf) Scale [Baseline and Week 12]

   The BPI-sf consists of 15 Items (Item 1:presence of pain; Item 2:pain location; Items 3 to 6:pain severity; Item 7:status of pain treatment; Item 8:efficacy of pain treatment; and Items 9a to 9g: interference of pain with daily life). Pain Sub-scale score ranges from 0 (absent [no pain]) to 10 (extreme [pain as bad as you can image]). Higher scores indicates worsening. Total score is defined as the mean scores from Items 3, 4, 5, 6 and 9 recorded on an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. Lower score indicates an improvement in pain.

7. Change From Baseline in Brief Pain Inventory (Short Form) (BPI-sf) Total Score at Week 12 [Baseline and Week 12]

   The BPI-sf consists of 15 Items (Item 1:presence of pain; Item 2:pain location; Items 3 to 6:pain severity; Item 7:status of pain treatment; Item 8:efficacy of pain treatment; and Items 9a to 9g: interference of pain with daily life). Total score is defined as the mean scores from Items 3, 4, 5, 6 and 9 recorded on an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. Lower score indicates an improvement in pain.

8. Change From Baseline in Sleep Latency Based on Sleep Questionnaire at Week 12 [Baseline and Week 12]

   Sleep Latency was related to "How long after bedtime or lights out did the participant fall asleep last night ". Decrease in time indicates an improvement.

9. Change From Baseline in Time Slept Based on Sleep Questionnaire at Week 12 [Baseline and Week 12]

   Time slept was related to "How long did the participant sleep last night". The mean change for the time in hours slept during the last night was reported.

10. Number of Participants With Awakenings Based on Sleep Questionnaire [Baseline and Week 12]

    Number of awakenings was related to "How many times did the participant wake up during the night". Lesser number signifies better sleep.

11. Number of Participants With Response Based on Overall Quality of Sleep Questionnaire [Baseline and Week 12]

    Participants rated the overall quality of sleep last night as excellent, good, fair and poor.

12. Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Scores at Week 12 [Baseline and Week 12]

    The SF-36v2 is 36-item form related to 8 health concepts (physical functioning, role physical, role emotional, general health, social functioning, bodily pain, vitality, mental health) and 2 summary scores (physical and mental component summary). Physical functioning, role physical and bodily pain contribute to physical component; role emotional, social functioning and mental health contribute to mental component; and social functioning, vitality, and general health contribute to both. All scores are based on a scale from 0 to 100, with higher scores defining more favorable health state.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants with chronic pain due to painful diabetic neuropathy or postherpetic neuralgia continuing for at least 12 weeks before consent

• Participants with adjuvant analgesics (antidepressants, antiepileptics and diabetic peripheral neuropathy drugs) or non-opioid treatment and dissatisfied with current treatment (in sense of efficacy and/or safety) for at least consecutive 14 days during the 12 weeks before consent

• Participants have not experienced treatment with conventional opioids, except for the following cases: Short term use of opioid analgesics for treatment of post-operative acute pain more than 30 days before consent; and temporal use of codeine phosphate or dihydrocodeine phosphate for purposes other than pain relief (for example, for antitussive) more than 2 days before consent

• Mean pain intensity score of greater than or equal to 5 on an 11-point Numerical Rating Scale during 48 hours before consent and the Investigator or Sub-investigator considers that the participant should be treated with an opioid analgesic

• HbA1c within 4 weeks before consent less than or equal to 11percent (in participants with diabetic neuropathic pain)

Exclusion Criteria:

• Participants have been treated or treated with a monoamine oxidase inhibitor within 14 days before consent

• Current or a history of epilepsy or convulsive disorders or hypersensitivity to opioid analgesics

• Suggested of intracranial hypertension (for example, traumatic encephalopathy)

• Participants who have complicated condition with uncontrolled or clinically significant arrhythmia, or neuropsychiatric disorders

• Participants with moderately to severely impaired hepatic function, or severely impaired renal function

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chigasaki		Japan
2		Chuo-Ku		Japan
3		Fukuoka		Japan
4		Inashiki		Japan
5		Isesaki		Japan
6		Izumisano		Japan
7		Kanuma		Japan
8		Katsushika-Ku		Japan
9		Kawaguchi		Japan
10		Kooriyama		Japan
11		Kurume		Japan
12		Kyoto		Japan
13		Matsue		Japan
14		Matsumoto		Japan
15		Minato-Ku		Japan
16		Mitaka		Japan
17		Nagano		Japan
18		Nagoya-City		Japan
19		Nagoya		Japan
20		Obihiro		Japan
21		Ohta-Ku		Japan
22		Ohtsu		Japan
23		Okayama		Japan
24		Omuta		Japan
25		Osaka		Japan
26		Sapporo		Japan
27		Sendai		Japan
28		Setagaya		Japan
29		Shimotsuga		Japan
30		Tokyo		Japan
31		Ube		Japan
32		Yokohama		Japan

Sponsors and Collaborators

• Janssen Pharmaceutical K.K.

Investigators

• Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Pharmaceutical K.K.
• ClinicalTrials.gov Identifier: NCT01124617
• Other Study ID Numbers: CR017002; JNS024ER-JPN-N22
• First Posted: May 17, 2010
• Last Update Posted: Jan 13, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by Janssen Pharmaceutical K.K.: Chronic pain; Diabetic Neuropathic Pain; Neuralgia, Postherpetic; Tapentadol hydrochloride extended-release; JNS024ER; Placebo
• Additional relevant MeSH terms: Neuralgia; Diabetic Neuropathies; Neuralgia, Postherpetic; Chronic Pain; Tapentadol

Study Results

Participant Flow

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Period Title: Overall Study
STARTED	60	31
COMPLETED	41	25
NOT COMPLETED	19	6

Baseline Characteristics

Arm/Group Title	Tapentadol	Placebo	Total
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.	Total of all reporting groups
Overall Participants	60	31	91
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.6 (12.98)	68.6 (11.60)	65.9 (12.61)
Sex: Female, Male (Count of Participants)
Female	26 43.3%	14 45.2%	40 44%
Male	34 56.7%	17 54.8%	51 56%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Average Numerical Rating Scale (NRS) Score at Week 12
Description	Participants were asked to assess the average pain intensity on an 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number on the scale applicable to their pain. Baseline pain score is defined as the average pain intensity score over the last 3 days prior to the randomization. Change from Baseline in NRS score is the mean NRS score at Week 12 minus mean NRS score at Baseline.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all the randomly assigned participants who received at least 1 dose of study drug and had at least 1 post-randomization efficacy data. Last observation carried forward (LOCF) method was used to impute missing values.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	31
Baseline	6.7 (1.15)	6.9 (1.35)
Change at Week 12	-2.6 (2.23)	-2.6 (2.65)

2. Secondary Outcome

Title	Change From Baseline in Average Numerical Rating Scale (NRS) Score at Week 1 to 11
Description	Participants were asked to assess the average pain intensity on an 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number on the scale applicable to their pain. Baseline pain score is defined as the average pain intensity score over the last 3 days prior to the randomization. Change from Baseline in NRS score is the mean NRS score at corresponding week minus mean NRS score at Baseline.
Time Frame	Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11

Outcome Measure Data

Analysis Population Description

FAS included all the randomly assigned participants who received at least 1 dose of study drug and had at least 1 post-randomization efficacy data.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	31
Change at Week 1	-0.7 (1.15)	-0.2 (0.52)
Change at Week 2	-1.1 (1.47)	-0.9 (1.47)
Change at Week 3	-1.5 (1.75)	-1.1 (1.59)
Change at Week 4	-1.8 (1.88)	-1.6 (1.78)
Change at Week 5	-2.1 (1.87)	-1.7 (2.09)
Change at Week 6	-2.3 (1.97)	-2.0 (2.41)
Change at Week 7	-2.3 (2.10)	-2.2 (2.55)
Change at Week 8	-2.4 (2.12)	-2.4 (2.50)
Change at Week 9	-2.5 (2.20)	-2.4 (2.56)
Change at Week 10	-2.6 (2.22)	-2.6 (2.51)
Change at Week 11	-2.6 (2.25)	-2.4 (2.66)

3. Secondary Outcome

Title	Percentage of Participants With Treatment Response Based on Numerical Rating Scale (NRS)
Description	Percentage of participants with treatment response in mean NRS score by greater than equal to 30 or 50 percent (%) in the last week from baseline were considered as responders. Participants were asked to assess the average pain intensity on an 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number applicable to their pain on the scale.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS included all the randomly assigned participants who received at least 1 dose of study drug and had at least 1 post-randomization efficacy data.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	31
Greater than or equal to 30% treatment response	48.3 80.5%	41.9 135.2%
Greater than or equal to 50% treatment response	33.3 55.5%	38.7 124.8%

4. Secondary Outcome

Title	Number of Participants With Categorical Scores on Patient's Global Impression of Change (PGIC) Scale
Description	The PGIC is a 7-point scale that requires the participants to assess how much their illness has improved or worsened relative to a Baseline state at the beginning of the intervention. The response options are 1 = very much improved, 2 = much improved, 3 = minimally improve, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Time Frame	Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who received study drug & had at least 1 post-randomization efficacy data. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure & 'n' signifies those participants who were evaluable for this measure at given time points.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	46	26
Week 8: Very Much Improved (n = 46, 26)	7 11.7%	4 12.9%
Week 8: Much Improved (n = 46, 26)	16 26.7%	7 22.6%
Week 8: Minimally Improved (n = 46, 26)	16 26.7%	10 32.3%
Week 8: No Change (n = 46, 26)	6 10%	2 6.5%
Week 8: Minimally Worse (n = 46, 26)	1 1.7%	2 6.5%
Week 8: Much Worse (n = 46, 26)	1 1.7%	1 3.2%
Week 8: Very Much Worse (n = 46, 26)	0 0%	0 0%
Week 12: Very Much Improved (n = 40, 25)	6 10%	2 6.5%
Week 12 : Much Improved (n = 40, 25)	18 30%	9 29%
Week 12 : Minimally Improved (n = 40, 25)	13 21.7%	11 35.5%
Week 12 : No Change (n = 40, 25)	2 3.3%	2 6.5%
Week 12 : Minimally Worse (n = 40, 25)	0 0%	0 0%
Week 12 : Much Worse (n = 40, 25)	1 1.7%	1 3.2%
Week 12 : Very Much Worse (n = 40, 25)	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants With Categorical Scores on Physician's Global Assessment Scale
Description	Physician's Global Assessment Scale assesses the therapeutic efficacy (effectiveness) of the study drug for pain control on a 2-point scale of "effective" and "ineffective".
Time Frame	Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who received study drug & had at least 1 post-randomization efficacy data. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure & 'n' signifies those participants who were evaluable for this measure at given time points.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	46	26
Week 8: Effective (n = 46, 26)	41 68.3%	19 61.3%
Week 8: Ineffective (n = 46, 26)	5 8.3%	7 22.6%
Week 12: Effective (n = 40, 25)	35 58.3%	20 64.5%
Week 12 : Ineffective (n = 40, 25)	5 8.3%	5 16.1%

6. Secondary Outcome

Title	Change From Baseline in Pain Interference Subscale Score Based on Brief Pain Inventory (Short Form) (BPI-sf) Scale
Description	The BPI-sf consists of 15 Items (Item 1:presence of pain; Item 2:pain location; Items 3 to 6:pain severity; Item 7:status of pain treatment; Item 8:efficacy of pain treatment; and Items 9a to 9g: interference of pain with daily life). Pain interference sub-scale score ranges from 0 (do not interfere) to 10 (completely interferes). Higher scores indicates worsening. Total score is defined as the mean scores from Items 3, 4, 5, 6 and 9 recorded on an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. Lower score indicates an improvement in pain.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who received study drug & had at least 1 post-randomization efficacy data. 'n' signifies those participants who were evaluable for this measure at given time points.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	31
Baseline (n=60, 31)	4.7 (2.13)	4.6 (2.20)
Week 12 (n=25,40)	-2.6 (1.92)	-2.1 (2.48)

7. Secondary Outcome

Title	Change From Baseline in Pain Subscale Score Based on Brief Pain Inventory (Short Form) (BPI-sf) Scale
Description	The BPI-sf consists of 15 Items (Item 1:presence of pain; Item 2:pain location; Items 3 to 6:pain severity; Item 7:status of pain treatment; Item 8:efficacy of pain treatment; and Items 9a to 9g: interference of pain with daily life). Pain Sub-scale score ranges from 0 (absent [no pain]) to 10 (extreme [pain as bad as you can image]). Higher scores indicates worsening. Total score is defined as the mean scores from Items 3, 4, 5, 6 and 9 recorded on an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. Lower score indicates an improvement in pain.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who received study drug & had at least 1 post-randomization efficacy data. 'n' signifies those participants who were evaluable for this measure at given time points.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	31
Baseline (n=60, 31)	6.2 (1.19)	6.3 (1.22)
Week 12 (n=25,40)	-3.0 (1.72)	-2.6 (2.35)

8. Secondary Outcome

Title	Change From Baseline in Brief Pain Inventory (Short Form) (BPI-sf) Total Score at Week 12
Description	The BPI-sf consists of 15 Items (Item 1:presence of pain; Item 2:pain location; Items 3 to 6:pain severity; Item 7:status of pain treatment; Item 8:efficacy of pain treatment; and Items 9a to 9g: interference of pain with daily life). Total score is defined as the mean scores from Items 3, 4, 5, 6 and 9 recorded on an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. Lower score indicates an improvement in pain.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all the randomly assigned participants who received at least 1 dose of study drug and had at least 1 post-randomization efficacy data. 'n' signifies those participants who were evaluable for this measure at given time points.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	31
Baseline (n=60,31)	5.2 (1.58)	5.2 (1.52)
Change at Week 12 (n=40,25)	-2.7 (1.64)	-2.3 (2.29)

9. Secondary Outcome

Title	Change From Baseline in Sleep Latency Based on Sleep Questionnaire at Week 12
Description	Sleep Latency was related to "How long after bedtime or lights out did the participant fall asleep last night ". Decrease in time indicates an improvement.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who received study drug & had at least 1 post-randomization efficacy data. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure & 'n' signifies those participants who were evaluable for this measure at given time points.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	30
Baseline (n=60, 30)	45.4 (65.78)	34.7 (28.62)
Change at Week 12 (n=40, 24)	-11.1 (49.15)	-3.1 (30.17)

10. Secondary Outcome

Title	Change From Baseline in Time Slept Based on Sleep Questionnaire at Week 12
Description	Time slept was related to "How long did the participant sleep last night". The mean change for the time in hours slept during the last night was reported.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all the randomly assigned participants who received at least 1 dose of study drug and had at least 1 post-randomization efficacy data. 'n' signifies those participants who were evaluable for this measure at given time points.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	31
Baseline (n=60, 31)	5.8 (1.29)	6.4 (1.97)
Change at Week 12 (n=40,25)	0.3 (1.71)	0.3 (1.58)

11. Secondary Outcome

Title	Number of Participants With Awakenings Based on Sleep Questionnaire
Description	Number of awakenings was related to "How many times did the participant wake up during the night". Lesser number signifies better sleep.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all the randomly assigned participants who received at least 1 dose of study drug and had at least 1 post-randomization efficacy data. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants who were evaluable for this measure at given time points.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	30
Baseline: 0 awakening (n=60,30)	17 28.3%	3 9.7%
Baseline: 1 awakening (n=60,30)	16 26.7%	9 29%
Baseline: 2 awakenings (n=60,30)	10 16.7%	10 32.3%
Baseline: 3 awakenings (n=60,30)	8 13.3%	6 19.4%
Baseline: 4 awakenings (n=60,30)	5 8.3%	1 3.2%
Baseline: > or = 5 awakenings (n=60,30)	4 6.7%	1 3.2%
Week 12 : 0 awakening (n=40,25)	12 20%	3 9.7%
Week 12 : 1 awakening (n=40,25)	14 23.3%	8 25.8%
Week 12 : 2 awakenings (n=40,25)	9 15%	7 22.6%
Week 12 : 3 awakenings (n=40,25)	1 1.7%	4 12.9%
Week 12 : 4 awakenings (n=40,25)	3 5%	2 6.5%
Week 12 : > or = 5 awakenings (n=40,25)	1 1.7%	1 3.2%

12. Secondary Outcome

Title	Number of Participants With Response Based on Overall Quality of Sleep Questionnaire
Description	Participants rated the overall quality of sleep last night as excellent, good, fair and poor.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all the randomly assigned participants who received at least 1 dose of study drug and had at least 1 post-randomization efficacy data. 'n' signifies those participants who were evaluable for this measure at given time points.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	31
Baseline: Excellent (n=60,31)	0 0%	1 3.2%
Baseline: Good (n=60,31)	35 58.3%	12 38.7%
Baseline: Fair (n=60,31)	22 36.7%	16 51.6%
Baseline: Poor (n=60,31)	3 5%	2 6.5%
Week 12 : Excellent (n=60,31)	4 6.7%	0 0%
Week 12 : Good (n=40,25)	28 46.7%	17 54.8%
Week 12 : Fair (n=40,25)	6 10%	8 25.8%
Week 12 : Poor (n=40,25)	2 3.3%	0 0%

13. Secondary Outcome

Title	Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Scores at Week 12
Description	The SF-36v2 is 36-item form related to 8 health concepts (physical functioning, role physical, role emotional, general health, social functioning, bodily pain, vitality, mental health) and 2 summary scores (physical and mental component summary). Physical functioning, role physical and bodily pain contribute to physical component; role emotional, social functioning and mental health contribute to mental component; and social functioning, vitality, and general health contribute to both. All scores are based on a scale from 0 to 100, with higher scores defining more favorable health state.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS included all the randomly assigned participants who received at least 1 dose of study drug and had at least 1 post-randomization efficacy data. 'n' signifies those participants who were evaluable for this measure at given time points.

Arm/Group Title	Tapentadol	Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.	Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
Measure Participants	60	31
Physical Functioning: Baseline (n=60,31)	68.6 (21.88)	61.0 (24.20)
Role-Physical: Baseline (n=60,31)	70.1 (27.95)	64.3 (28.15)
Bodily Pain: Baseline (n=60,31)	36.2 (16.74)	38.8 (14.50)
General Health: Baseline (n=60,31)	45.7 (16.73)	44.7 (17.51)
Vitality: Baseline (n=60,31)	48.8 (23.49)	50.4 (22.47)
Social Functioning: Baseline (n=60,31)	72.9 (26.66)	80.2 (27.72)
Role-Emotional: Baseline (n=60,31)	68.9 (30.91)	68.5 (28.19)
Mental Health: Baseline (n=60,31)	57.6 (24.54)	61.8 (22.04)
Mental Summary: Baseline (n=60,31)	43.9 (12.27)	47.6 (10.65)
Physical Summary: Baseline (n=60,31)	36.0 (16.11)	31.7 (16.48)
Physical Functioning: Change at Week 12 (n=40,25)	5.4 (13.65)	4.8 (14.89)
Role-Physical: Change at Week 12 (n=40,25)	6.6 (21.74)	4.8 (22.26)
Bodily Pain: Change at Week 12 (n=40,25)	10.5 (15.43)	7.0 (15.57)
General Health: Change at Week 12 (n=40,25)	-0.4 (10.74)	0.2 (11.83)
Vitality: Change at Week 12 (n=40,25)	9.4 (19.09)	6.8 (22.31)
Social Functioning: Change at Week 12 (n=40,25)	8.1 (21.47)	2.0 (37.27)
Role-Emotional: Change at Week 12 (n=40,25)	6.0 (27.02)	5.7 (25.65)
Mental Health: Change at Week 12 (n=40,25)	7.8 (17.02)	9.0 (23.98)
Mental Summary: Change at Week 12 (n=40,25)	4.5 (7.85)	3.3 (11.48)
Physical Summary: Change at Week 12 (n=40,25)	4.4 (11.22)	2.8 (11.56)

Adverse Events

Time Frame	Baseline up to Week 12
Adverse Event Reporting Description	An adverse event is any untoward medical occurrence in a clinical study participant administered with study treatment. It can be any unfavorable and unintended sign/abnormal finding, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Arm/Group Title	Tapentadol		Placebo
Arm/Group Description	Tapentadol hydrochloride extended-release(ER) was administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.		Matching Placebo was administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.
All Cause Mortality
	Tapentadol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tapentadol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/60 (6.7%)		3/31 (9.7%)
Cardiac disorders
Angina pectoris	1/60 (1.7%)		0/31 (0%)
Gastrointestinal disorders
Vomiting	1/60 (1.7%)		0/31 (0%)
General disorders
Drug withdrawal syndrome	1/60 (1.7%)		0/31 (0%)
Infections and infestations
Urinary tract infection	0/60 (0%)		1/31 (3.2%)
Nervous system disorders
Loss of consciousness	0/60 (0%)		1/31 (3.2%)
Psychiatric disorders
Delirium	1/60 (1.7%)		0/31 (0%)
Skin and subcutaneous tissue disorders
Diabetic ulcer	0/60 (0%)		1/31 (3.2%)
Other (Not Including Serious) Adverse Events
	Tapentadol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/60 (86.7%)		26/31 (83.9%)
Blood and lymphatic system disorders
Anaemia	0/60 (0%)		1/31 (3.2%)
Iron deficiency anaemia	1/60 (1.7%)		0/31 (0%)
Ear and labyrinth disorders
Motion sickness	1/60 (1.7%)		0/31 (0%)
Endocrine disorders
Hypothyroidism	0/60 (0%)		1/31 (3.2%)
Eye disorders
Retinal haemorrhage	1/60 (1.7%)		1/31 (3.2%)
Chalazion	0/60 (0%)		1/31 (3.2%)
Diabetic retinopathy	1/60 (1.7%)		0/31 (0%)
Macular oedema	0/60 (0%)		1/31 (3.2%)
Ocular hyperaemia	0/60 (0%)		1/31 (3.2%)
Trichiasis	0/60 (0%)		1/31 (3.2%)
Gastrointestinal disorders
Nausea	19/60 (31.7%)		0/31 (0%)
Constipation	16/60 (26.7%)		0/31 (0%)
Vomiting	11/60 (18.3%)		1/31 (3.2%)
Diarrhoea	4/60 (6.7%)		2/31 (6.5%)
Abdominal discomfort	4/60 (6.7%)		1/31 (3.2%)
Abdominal distension	0/60 (0%)		1/31 (3.2%)
Dry mouth	1/60 (1.7%)		0/31 (0%)
Gastritis	1/60 (1.7%)		0/31 (0%)
Irritable bowel syndrome	0/60 (0%)		1/31 (3.2%)
Periodontitis	1/60 (1.7%)		0/31 (0%)
Stomatitis	1/60 (1.7%)		0/31 (0%)
General disorders
Drug withdrawal syndrome	5/60 (8.3%)		0/31 (0%)
Thirst	5/60 (8.3%)		0/31 (0%)
Malaise	3/60 (5%)		1/31 (3.2%)
Pain	1/60 (1.7%)		1/31 (3.2%)
Pyrexia	2/60 (3.3%)		0/31 (0%)
Asthenia	0/60 (0%)		1/31 (3.2%)
Chest pain	1/60 (1.7%)		0/31 (0%)
Fatigue	0/60 (0%)		1/31 (3.2%)
Feeling abnormal	1/60 (1.7%)		0/31 (0%)
Feeling hot	1/60 (1.7%)		0/31 (0%)
Irritability	1/60 (1.7%)		0/31 (0%)
Oedema	1/60 (1.7%)		0/31 (0%)
Hepatobiliary disorders
Hepatic function abnormal	1/60 (1.7%)		1/31 (3.2%)
Infections and infestations
Nasopharyngitis	7/60 (11.7%)		4/31 (12.9%)
Gastroenteritis	3/60 (5%)		1/31 (3.2%)
Cystitis	0/60 (0%)		1/31 (3.2%)
Herpes simplex	1/60 (1.7%)		0/31 (0%)
Otitis media	1/60 (1.7%)		0/31 (0%)
Sinusitis	0/60 (0%)		1/31 (3.2%)
Tinea pedis	0/60 (0%)		1/31 (3.2%)
Tonsillitis	0/60 (0%)		1/31 (3.2%)
Upper respiratory tract infection	1/60 (1.7%)		0/31 (0%)
Injury, poisoning and procedural complications
Fall	1/60 (1.7%)		0/31 (0%)
Wound	1/60 (1.7%)		0/31 (0%)
Investigations
Blood urine present	3/60 (5%)		0/31 (0%)
Liver function test abnormal	2/60 (3.3%)		1/31 (3.2%)
Blood creatine phosphokinase increased	2/60 (3.3%)		0/31 (0%)
Blood pressure increased	1/60 (1.7%)		1/31 (3.2%)
Protein urine present	2/60 (3.3%)		0/31 (0%)
Electrocardiogram ST segment depression	1/60 (1.7%)		0/31 (0%)
Gamma-glutamyltransferase increased	1/60 (1.7%)		0/31 (0%)
Glycosylated haemoglobin increased	0/60 (0%)		1/31 (3.2%)
Neutrophil count increased	1/60 (1.7%)		0/31 (0%)
White blood cell count increased	1/60 (1.7%)		0/31 (0%)
Eosinophil percentage increased	0/60 (0%)		1/31 (3.2%)
Lymphocyte percentage decreased	1/60 (1.7%)		0/31 (0%)
Blood alkaline phosphatase increased	1/60 (1.7%)		0/31 (0%)
Metabolism and nutrition disorders
Decreased appetite	9/60 (15%)		1/31 (3.2%)
Hypoglycaemia	2/60 (3.3%)		0/31 (0%)
Dehydration	0/60 (0%)		1/31 (3.2%)
Hyperglycaemia	1/60 (1.7%)		0/31 (0%)
Hyperlipidaemia	1/60 (1.7%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/60 (0%)		1/31 (3.2%)
Muscular weakness	0/60 (0%)		1/31 (3.2%)
Pain in extremity	1/60 (1.7%)		0/31 (0%)
Spinal osteoarthritis	1/60 (1.7%)		0/31 (0%)
Facet joint syndrome	1/60 (1.7%)		0/31 (0%)
Nervous system disorders
Somnolence	17/60 (28.3%)		3/31 (9.7%)
Dizziness	5/60 (8.3%)		2/31 (6.5%)
Headache	4/60 (6.7%)		2/31 (6.5%)
Autonomic nervous system imbalance	1/60 (1.7%)		0/31 (0%)
Dizziness postural	1/60 (1.7%)		0/31 (0%)
Radial nerve palsy	1/60 (1.7%)		0/31 (0%)
Psychiatric disorders
Insomnia	5/60 (8.3%)		0/31 (0%)
Anxiety	1/60 (1.7%)		0/31 (0%)
Depression	1/60 (1.7%)		0/31 (0%)
Listless	1/60 (1.7%)		0/31 (0%)
Renal and urinary disorders
Dysuria	1/60 (1.7%)		0/31 (0%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	2/60 (3.3%)		0/31 (0%)
Dyspnoea	1/60 (1.7%)		0/31 (0%)
Hypoventilation	1/60 (1.7%)		0/31 (0%)
Rhinitis allergic	1/60 (1.7%)		0/31 (0%)
Tachypnoea	0/60 (0%)		1/31 (3.2%)
Skin and subcutaneous tissue disorders
Xeroderma	2/60 (3.3%)		1/31 (3.2%)
Eczema	2/60 (3.3%)		0/31 (0%)
Erythema	2/60 (3.3%)		0/31 (0%)
Pruritus	2/60 (3.3%)		0/31 (0%)
Rash	2/60 (3.3%)		0/31 (0%)
Dermatitis	1/60 (1.7%)		0/31 (0%)
Hyperhidrosis	1/60 (1.7%)		0/31 (0%)
Ingrowing nail	1/60 (1.7%)		0/31 (0%)
Prurigo	1/60 (1.7%)		0/31 (0%)
Pruritus generalised	1/60 (1.7%)		0/31 (0%)
Vascular disorders
Hypertension	2/60 (3.3%)		0/31 (0%)
Hypotension	1/60 (1.7%)		0/31 (0%)
Hot flush	1/60 (1.7%)		0/31 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.