Trial Outcomes & Findings for An Efficacy and Safety Study of Extended Release (ER) Tramadol Hydrochloride (HCl)/Acetaminophen in Participants With Chronic Low-Back Pain (NCT NCT01112267)

NCT ID: NCT01112267

Last Updated: 2013-07-24

Results Overview

The percentage of participants with extent of reduction in pain intensity greater than or equal to 30 percent was reported. Pain intensity change rate was calculated by Visual Analog Scale (VAS) score at baseline minus VAS score at Day 29 divided by VAS score at Baseline. VAS is a 10 centimeter (cm) scale. Intensity of pain range: 0 cm=no pain to 10 cm=worst possible pain.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

248 participants

Primary outcome timeframe

Baseline up to Day 29

Results posted on

2013-07-24

Participant Flow

Participant milestones

Participant milestones
Measure
Tramadol HCl/Acetaminophen
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Overall Study
STARTED
126
122
Overall Study
Treated
125
120
Overall Study
COMPLETED
92
104
Overall Study
NOT COMPLETED
34
18

Reasons for withdrawal

Reasons for withdrawal
Measure
Tramadol HCl/Acetaminophen
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Overall Study
Adverse Event
24
6
Overall Study
Withdrawal by Subject
3
5
Overall Study
Protocol Violation
5
3
Overall Study
Participants not compliant
1
2
Overall Study
Participants not receive any study drug
1
2

Baseline Characteristics

An Efficacy and Safety Study of Extended Release (ER) Tramadol Hydrochloride (HCl)/Acetaminophen in Participants With Chronic Low-Back Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Tramadol HCl/Acetaminophen
n=125 Participants
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
n=120 Participants
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Total
n=245 Participants
Total of all reporting groups
Age Continuous
59.93 Years
STANDARD_DEVIATION 10.72 • n=5 Participants
60.39 Years
STANDARD_DEVIATION 9.87 • n=7 Participants
60.16 Years
STANDARD_DEVIATION 10.29 • n=5 Participants
Sex: Female, Male
Female
94 Participants
n=5 Participants
89 Participants
n=7 Participants
183 Participants
n=5 Participants
Sex: Female, Male
Male
31 Participants
n=5 Participants
31 Participants
n=7 Participants
62 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 29

Population: Full analysis set (FAS) population included all participants who had received investigational product and had at least 1 data of measurement of primary efficacy endpoint.

The percentage of participants with extent of reduction in pain intensity greater than or equal to 30 percent was reported. Pain intensity change rate was calculated by Visual Analog Scale (VAS) score at baseline minus VAS score at Day 29 divided by VAS score at Baseline. VAS is a 10 centimeter (cm) scale. Intensity of pain range: 0 cm=no pain to 10 cm=worst possible pain.

Outcome measures

Outcome measures
Measure
Tramadol HCl/Acetaminophen
n=85 Participants
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
n=90 Participants
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Percentage of Participants With Reduction in Pain Intensity
57.65 Percentage of Participants
Interval 47.14 to 68.15
41.11 Percentage of Participants
Interval 30.95 to 51.28

PRIMARY outcome

Timeframe: Baseline and Day 29

Population: The FAS population included all the participants who had received investigational product and had at least 1 data of measurement of primary efficacy endpoint.

Change in pain intensity experienced by participants over the last 48 hours was measured on Day 29 against Baseline with VAS. VAS is a 10 cm scale. Intensity of pain range: 0 cm=no pain to 10 cm=worst possible pain.

Outcome measures

Outcome measures
Measure
Tramadol HCl/Acetaminophen
n=85 Participants
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
n=90 Participants
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Change From Baseline in Pain Intensity at Day 29
Baseline
6.334 Unit on a scale
Standard Deviation 1.383
6.000 Unit on a scale
Standard Deviation 1.331
Change From Baseline in Pain Intensity at Day 29
Change at Day 29
2.299 Unit on a scale
Standard Deviation 1.764
1.549 Unit on a scale
Standard Deviation 1.578

SECONDARY outcome

Timeframe: Day 8, Day 15 and Day 29

Population: the FAS population included all the participants who had received investigational product and had at least 1 data of measurement of primary efficacy endpoint.

Pain relief was measured in 6 stages to assess the participant's pain relief. Extent of pain relief was measured on a scale ranging from 4 to -1, where 4=complete disappearance, 3=fair relief, 2=moderate relief, 1=slight relief, 0=no change and -1=pain worsening. Relief more than 'slight relief (1)' was considered as pain relief success.

Outcome measures

Outcome measures
Measure
Tramadol HCl/Acetaminophen
n=85 Participants
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
n=90 Participants
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Percentage of Participants With Pain Relief
Day 8: Slight relief (n=82,88)
70.73 Percentage of participants
Interval 60.88 to 80.58
53.41 Percentage of participants
Interval 42.99 to 63.83
Percentage of Participants With Pain Relief
Day 15: Slight relief (n=85,89)
82.35 Percentage of participants
Interval 74.25 to 90.46
65.17 Percentage of participants
Interval 55.27 to 75.07
Percentage of Participants With Pain Relief
Day 29, Slight relief (85,89)
81.18 Percentage of participants
Interval 72.87 to 89.49
77.53 Percentage of participants
Interval 68.86 to 86.2

SECONDARY outcome

Timeframe: Baseline and Day 29

Population: The FAS population included all the participants who had received investigational product and had at least 1 data of measurement of primary efficacy endpoint.

The quality of life of participants was evaluated by SF-36 Korean version questionnaire. It is composed of 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Participants answered to the questionnaire of 36 questions; and physical, social, and psychological health status were assessed. It ranges 0 to 100, and higher score indicates better quality of life, But in "Reported (Rptd.) Health Transition" domain higher score indicates worse quality of life.

Outcome measures

Outcome measures
Measure
Tramadol HCl/Acetaminophen
n=85 Participants
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
n=90 Participants
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Change From Baseline in Short Form (SF)-36 Score at Day 29
Baseline: Physical functioning
46.71 Unit on a scale
Standard Deviation 20.71
47.94 Unit on a scale
Standard Deviation 20.80
Change From Baseline in Short Form (SF)-36 Score at Day 29
Change at Day 29: Physical functioning (n=83,87)
9.82 Unit on a scale
Standard Deviation 18.35
6.67 Unit on a scale
Standard Deviation 15.99
Change From Baseline in Short Form (SF)-36 Score at Day 29
Baseline: Role physical
44.93 Unit on a scale
Standard Deviation 24.18
49.51 Unit on a scale
Standard Deviation 26.17
Change From Baseline in Short Form (SF)-36 Score at Day 29
Change at Day 29: Role Physical (n=83,87)
16.04 Unit on a scale
Standard Deviation 23.89
8.69 Unit on a scale
Standard Deviation 22.62
Change From Baseline in Short Form (SF)-36 Score at Day 29
Baseline: Bodily pain
34.66 Unit on a scale
Standard Deviation 14.46
35.99 Unit on a scale
Standard Deviation 13.89
Change From Baseline in Short Form (SF)-36 Score at Day 29
Change at Day 29: Bodily pain (n=83,87)
19.39 Unit on a scale
Standard Deviation 18.99
17.69 Unit on a scale
Standard Deviation 14.84
Change From Baseline in Short Form (SF)-36 Score at Day 29
Baseline: General health
43.56 Unit on a scale
Standard Deviation 17.92
48.11 Unit on a scale
Standard Deviation 17.05
Change From Baseline in Short Form (SF)-36 Score at Day 29
Change at Day 29: General health (n=83,87)
7.36 Unit on a scale
Standard Deviation 14.41
2.77 Unit on a scale
Standard Deviation 12.58
Change From Baseline in Short Form (SF)-36 Score at Day 29
Baseline: Vitality
38.82 Unit on a scale
Standard Deviation 19.93
42.71 Unit on a scale
Standard Deviation 17.83
Change From Baseline in Short Form (SF)-36 Score at Day 29
Change at Day 29: Vitality (n=83,87)
11.14 Unit on a scale
Standard Deviation 20.55
5.82 Unit on a scale
Standard Deviation 18.94
Change From Baseline in Short Form (SF)-36 Score at Day 29
Baseline: Social functioning
64.26 Unit on a scale
Standard Deviation 22.59
64.58 Unit on a scale
Standard Deviation 26.98
Change From Baseline in Short Form (SF)-36 Score at Day 29
Change at Day 29: Social functioning (n=83,87)
11.75 Unit on a scale
Standard Deviation 25.70
6.61 Unit on a scale
Standard Deviation 20.60
Change From Baseline in Short Form (SF)-36 Score at Day 29
Baseline: Role emotional
61.76 Unit on a scale
Standard Deviation 27.41
61.57 Unit on a scale
Standard Deviation 29.34
Change From Baseline in Short Form (SF)-36 Score at Day 29
Change at Day 29: Role emotional (n=83,87)
8.13 Unit on a scale
Standard Deviation 28.93
7.47 Unit on a scale
Standard Deviation 28.25
Change From Baseline in Short Form (SF)-36 Score at Day 29
Baseline: Mental Health
61.06 Unit on a scale
Standard Deviation 19.03
60.56 Unit on a scale
Standard Deviation 19.34
Change From Baseline in Short Form (SF)-36 Score at Day 29
Change at Day 29: Mental Health (n=83,87)
20.48 Unit on a scale
Standard Deviation 23.20
18.39 Unit on a scale
Standard Deviation 24.61
Change From Baseline in Short Form (SF)-36 Score at Day 29
Baseline: Rptd. health transition
65.00 Unit on a scale
Standard Deviation 24.76
63.61 Unit on a scale
Standard Deviation 20.92
Change From Baseline in Short Form (SF)-36 Score at Day 29
Change at Day 29: Rptd. health transition(n=83,87)
-18.07 Unit on a scale
Standard Deviation 25.99
-6.90 Unit on a scale
Standard Deviation 30.19

SECONDARY outcome

Timeframe: Baseline and Day 29

Population: FAS population included all participants who had received investigational product and had at least 1 data of measurement of primary efficacy endpoint.

The ODI Korean version was used to assess the participant's functionality. The ODI is a low back pain-specific, validated instrument that consists of questions related to limitations in performing specific activities of daily living and 1 question related to pain intensity. The ODI is a self-administered questionnaire consists of 10 sections. Each section consists of 6 statements ranked from 0 to 5 (0=good to 5=worse). Total score is the sum of score obtained in each section and ranges from 0 to 50. A higher score represents greater disability.

Outcome measures

Outcome measures
Measure
Tramadol HCl/Acetaminophen
n=85 Participants
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
n=90 Participants
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Change From Baseline in Oswestry Disability Index (ODI) Korean Version Score at Day 29
Baseline
39.626 Unit on a scale
Standard Deviation 12.239
38.126 Unit on a scale
Standard Deviation 13.518
Change From Baseline in Oswestry Disability Index (ODI) Korean Version Score at Day 29
Change at Day 29 (n=87,83)
11.216 Unit on a scale
Standard Deviation 11.856
7.178 Unit on a scale
Standard Deviation 13.879

SECONDARY outcome

Timeframe: Day 29

Population: The FAS population included all the participants who had received investigational product and had at least 1 data of measurement of primary efficacy endpoint. Here 'N' signifies those participants who were evaluated for this outcome measure.

Global assessment on investigational product was done by investigator on how well the investigational product controlled chronic (lasting a long time) low back pain. Assessment was done by categories 'Very bad (-2)' 'Bad (-1)' 'Not changed (0) 'Good (1)' and 'Very good (2)'. Assessment better than "Good" was considered as pain improvement success. Percentage of participants with pain improvement success is reported here.

Outcome measures

Outcome measures
Measure
Tramadol HCl/Acetaminophen
n=80 Participants
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
n=83 Participants
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Percentage of Participants With Investigator's Global Assessment on Investigational Product
81.25 Percentage of participants
Interval 72.7 to 89.8
69.88 Percentage of participants
Interval 60.01 to 79.75

SECONDARY outcome

Timeframe: Day 29

Population: The FAS population included all the participants who had received investigational product and had at least 1 data of measurement of primary efficacy endpoint. Here 'N' signifies those participants who were evaluated for this outcome measure.

Global assessment on investigational product was done by participants on how well the investigational product controlled chronic (lasting a long time) low back pain. Assessment was done by categories 'Very bad (-2)' 'Bad (-1)' 'Not changed (0) 'Good (1)' and 'Very good (2)'. Assessment better than "Good" was considered as pain improvement success. Percentage of participants with pain improvement success is reported here.

Outcome measures

Outcome measures
Measure
Tramadol HCl/Acetaminophen
n=80 Participants
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
n=83 Participants
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Percentage of Participants With Participants' Global Assessment on Investigational Product
76.25 Percentage of participants
Interval 66.92 to 85.58
72.29 Percentage of participants
Interval 62.66 to 81.92

Adverse Events

Tramadol HCl/Acetaminophen

Serious events: 1 serious events
Other events: 102 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 52 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Tramadol HCl/Acetaminophen
n=125 participants at risk
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
n=120 participants at risk
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
0.80%
1/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29

Other adverse events

Other adverse events
Measure
Tramadol HCl/Acetaminophen
n=125 participants at risk
Participants received 1 tablet containing fixed dose of combination of tramadol hydrochloride (HCl) 75 milligram (mg) /acetaminophen Extended Release (ER) 650 mg orally once daily on Days 1 to 3, 1 tablet twice daily (tramadol HCl 150 mg/acetaminophen 1300 mg) on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Placebo
n=120 participants at risk
Participants received 1 tablet of matching placebo once daily orally on Days 1 to 3, 1 tablet twice daily on Days 4 to 7, then 1 or 2 tablets twice daily on Days 8 to 28.
Infections and infestations
Nasopharyngitis
0.00%
0/125 • Baseline up to Day 29
2.5%
3/120 • Baseline up to Day 29
Musculoskeletal and connective tissue disorders
Myalgia
0.00%
0/125 • Baseline up to Day 29
2.5%
3/120 • Baseline up to Day 29
Metabolism and nutrition disorders
Decreased appetite
4.8%
6/125 • Baseline up to Day 29
3.3%
4/120 • Baseline up to Day 29
Nervous system disorders
Headache
8.8%
11/125 • Baseline up to Day 29
5.0%
6/120 • Baseline up to Day 29
Nervous system disorders
Dizziness
27.2%
34/125 • Baseline up to Day 29
8.3%
10/120 • Baseline up to Day 29
Nervous system disorders
Somnolence
14.4%
18/125 • Baseline up to Day 29
3.3%
4/120 • Baseline up to Day 29
Renal and urinary disorders
Dysuria
3.2%
4/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29
Gastrointestinal disorders
Dry mouth
4.0%
5/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29
Gastrointestinal disorders
Nausea
36.0%
45/125 • Baseline up to Day 29
10.0%
12/120 • Baseline up to Day 29
Gastrointestinal disorders
Constipation
18.4%
23/125 • Baseline up to Day 29
3.3%
4/120 • Baseline up to Day 29
Gastrointestinal disorders
Abdominal pain
2.4%
3/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29
Gastrointestinal disorders
Dyspepsia
10.4%
13/125 • Baseline up to Day 29
10.0%
12/120 • Baseline up to Day 29
General disorders
Thirst
2.4%
3/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29
Psychiatric disorders
Insomnia
4.8%
6/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29
Skin and subcutaneous tissue disorders
Pruritus
14.4%
18/125 • Baseline up to Day 29
3.3%
4/120 • Baseline up to Day 29
Skin and subcutaneous tissue disorders
Hyperhidrosis
3.2%
4/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29
Skin and subcutaneous tissue disorders
Urticaria
2.4%
3/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29
Skin and subcutaneous tissue disorders
Rash
2.4%
3/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29
Skin and subcutaneous tissue disorders
Cold sweating
2.4%
3/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29
Gastrointestinal disorders
Vomiting
16.8%
21/125 • Baseline up to Day 29
4.2%
5/120 • Baseline up to Day 29
Gastrointestinal disorders
Abdominal discomfort
0.00%
0/125 • Baseline up to Day 29
3.3%
4/120 • Baseline up to Day 29
General disorders
Face oedema
2.4%
3/125 • Baseline up to Day 29
0.00%
0/120 • Baseline up to Day 29

Additional Information

Therapeutic area Scientist

Janssen Korea/ Seoul

Phone: +82-2-2094-4802

Results disclosure agreements

  • Principal investigator is a sponsor employee PI cannot provide the any trial related information to external parties' without mutual agreement with the sponsor. This is valid even after the contract is canceled.
  • Publication restrictions are in place

Restriction type: OTHER