Trial Outcomes & Findings for A Study to Evaluate the Efficacy, Safety, and Tolerability of Tapentadol ER Compared With Placebo in Patients With Chronic, Painful Diabetic Peripheral Neuropathy (NCT NCT01041859)
NCT ID: NCT01041859
Last Updated: 2013-09-11
Results Overview
For this twice daily pain assessment, the patients were to indicate the level of pain experienced over the previous 12 hours on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
460 participants
Primary outcome timeframe
Double-Blind Baseline and 12 weeks (Primary endpoint is the average pain intensity score during the last week of the maintenance period)
Results posted on
2013-09-11
Participant Flow
In a 3-week open-label (OL) period, patients titrated to an optimal dose between 100 mg and 250 mg twice daily. Patients with \>=1-point reduction in pain intensity at the end of OL period were randomized. 38 of 358 who completed OL were not randomized: \<1-pt reduction(28), withdrew consent(4), non-compliant(2), adverse events(1), other reason(3).
Participant milestones
| Measure |
OL Tapentadol
Tapentadol extended release (ER) 50 100 150 200 250 mg twice daily for 3 weeks
|
DB Tapentadol ER
Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 12 weeks
|
DB Placebo
Double-Blind Placebo Control Group
|
|---|---|---|---|
|
Open-Label Titration
STARTED
|
459
|
0
|
0
|
|
Open-Label Titration
COMPLETED
|
358
|
0
|
0
|
|
Open-Label Titration
NOT COMPLETED
|
101
|
0
|
0
|
|
Double-Blind Maintenance
STARTED
|
0
|
166
|
152
|
|
Double-Blind Maintenance
COMPLETED
|
0
|
120
|
107
|
|
Double-Blind Maintenance
NOT COMPLETED
|
0
|
46
|
45
|
Reasons for withdrawal
| Measure |
OL Tapentadol
Tapentadol extended release (ER) 50 100 150 200 250 mg twice daily for 3 weeks
|
DB Tapentadol ER
Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 12 weeks
|
DB Placebo
Double-Blind Placebo Control Group
|
|---|---|---|---|
|
Open-Label Titration
Adverse Event
|
69
|
0
|
0
|
|
Open-Label Titration
Lack of Efficacy
|
3
|
0
|
0
|
|
Open-Label Titration
Lost to Follow-up
|
1
|
0
|
0
|
|
Open-Label Titration
Physician Decision
|
1
|
0
|
0
|
|
Open-Label Titration
Protocol Violation
|
1
|
0
|
0
|
|
Open-Label Titration
Other
|
7
|
0
|
0
|
|
Open-Label Titration
Noncompliance With Study Drug
|
8
|
0
|
0
|
|
Open-Label Titration
Withdrawal by Subject
|
11
|
0
|
0
|
|
Double-Blind Maintenance
Adverse Event
|
0
|
23
|
13
|
|
Double-Blind Maintenance
Lack of Efficacy
|
0
|
3
|
11
|
|
Double-Blind Maintenance
Lost to Follow-up
|
0
|
1
|
0
|
|
Double-Blind Maintenance
Physician Decision
|
0
|
2
|
1
|
|
Double-Blind Maintenance
Protocol Violation
|
0
|
1
|
3
|
|
Double-Blind Maintenance
Other
|
0
|
6
|
2
|
|
Double-Blind Maintenance
Noncompliance With Study Drug
|
0
|
2
|
6
|
|
Double-Blind Maintenance
Withdrawal by Subject
|
0
|
8
|
9
|
Baseline Characteristics
A Study to Evaluate the Efficacy, Safety, and Tolerability of Tapentadol ER Compared With Placebo in Patients With Chronic, Painful Diabetic Peripheral Neuropathy
Baseline characteristics by cohort
| Measure |
DB Tapentadol ER
n=166 Participants
Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 12 weeks
|
DB Placebo
n=152 Participants
Double-Blind Placebo Control Group
|
Total
n=318 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
122 Participants
n=5 Participants
|
109 Participants
n=7 Participants
|
231 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
44 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Age Continuous
|
58.5 years
STANDARD_DEVIATION 10.63 • n=5 Participants
|
59 years
STANDARD_DEVIATION 9.00 • n=7 Participants
|
58.7 years
STANDARD_DEVIATION 9.87 • n=5 Participants
|
|
Sex: Female, Male
Female
|
67 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
131 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
99 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
187 Participants
n=5 Participants
|
|
Region Enroll
Canada
|
24 participants
n=5 Participants
|
22 participants
n=7 Participants
|
46 participants
n=5 Participants
|
|
Region Enroll
USA
|
142 participants
n=5 Participants
|
130 participants
n=7 Participants
|
272 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Double-Blind Baseline and 12 weeks (Primary endpoint is the average pain intensity score during the last week of the maintenance period)Population: Intent-to-treat (ITT) population. Last observation carried forward (LOCF) was used to impute pain score after discontinuation
For this twice daily pain assessment, the patients were to indicate the level of pain experienced over the previous 12 hours on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine".
Outcome measures
| Measure |
DB Tapentadol ER
n=165 Participants
Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 12 weeks
|
DB Placebo
n=152 Participants
Double-Blind Placebo Control Group
|
|---|---|---|
|
Change From Double-Blind Baseline of the Average Pain Intensity Based on an 11-point Numerical Rating Scale(NRS) Over the Last Week of the Maintenance Period at Week 12
|
0.28 units on a scale
Standard Deviation 2.04
|
1.3 units on a scale
Standard Deviation 2.43
|
SECONDARY outcome
Timeframe: Open-label Baseline and End of Double-Blind Treatment at 15 Weeks (3 weeks open-label plus 12 weeks double-blind)Population: Intent-to-treat (ITT) population. Last observation carried forward (LOCF) was used to impute pain score after discontinuation.
The NRS was a twice-daily pain assessment in which patients were to indicate the level of pain experienced over the previous 12 hours on an 11-point scale with a score of 0 indicating "no pain" and a score of 10 indicating "pain as bad as you can imagine".
Outcome measures
| Measure |
DB Tapentadol ER
n=166 Participants
Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 12 weeks
|
DB Placebo
n=152 Participants
Double-Blind Placebo Control Group
|
|---|---|---|
|
Responder Analysis: Proportion of Patients With At Least 50% Improvement From Baseline of Open-Label on the Numerical Rating Scale (NRS) at the Week 12 Endpoint
|
40.4 percentage of participants
2.04
|
28.9 percentage of participants
2.43
|
SECONDARY outcome
Timeframe: End of Double-Blind Treatment at 12 WeeksPopulation: Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point
Patient Global Impression of Change (PGIC) is a patient-rated assessment of overall neuropathic pain since the start of treatment using a categorical scale 1-7, where 1 is 'very much improved' and 7 is 'very much worse'
Outcome measures
| Measure |
DB Tapentadol ER
n=150 Participants
Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 12 weeks
|
DB Placebo
n=139 Participants
Double-Blind Placebo Control Group
|
|---|---|---|
|
Distribution of Patient Global Impression of Change at Week 12 Endpoint
Very much improved
|
28.7 percentage of participants
2.04
|
14.4 percentage of participants
2.43
|
|
Distribution of Patient Global Impression of Change at Week 12 Endpoint
Much improved
|
37.3 percentage of participants
|
30.9 percentage of participants
|
|
Distribution of Patient Global Impression of Change at Week 12 Endpoint
Minimally improved
|
21.3 percentage of participants
|
20.9 percentage of participants
|
|
Distribution of Patient Global Impression of Change at Week 12 Endpoint
Not changed
|
8.0 percentage of participants
|
18.7 percentage of participants
|
|
Distribution of Patient Global Impression of Change at Week 12 Endpoint
Minimally worse
|
2.0 percentage of participants
|
5.0 percentage of participants
|
|
Distribution of Patient Global Impression of Change at Week 12 Endpoint
Much worse
|
1.3 percentage of participants
|
7.9 percentage of participants
|
|
Distribution of Patient Global Impression of Change at Week 12 Endpoint
Very much worse
|
1.3 percentage of participants
|
2.2 percentage of participants
|
SECONDARY outcome
Timeframe: Open-label Baseline and End of Double-Blind Treatment at 15 Weeks (3 weeks open-label plus 12 weeks double-blind)Population: Intent-to-treat (ITT) population. Last observation carried forward (LOCF) endpoint.
The BPI is a 12-item questionnaire to evaluate the intensity of pain and the degree to which pain interferes with function. It includes 4 items assessing current pain intensity and pain at its worst, least, and on average over the past day using an 11-point scale from 0 = no pain to 10 = pain as bad as you can imagine. The pain intensity subscale score is defined as the mean of the scores from these 4 items.
Outcome measures
| Measure |
DB Tapentadol ER
n=147 Participants
Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 12 weeks
|
DB Placebo
n=137 Participants
Double-Blind Placebo Control Group
|
|---|---|---|
|
Change From Baseline of Open-Label in the Pain Intensity Subscale of the Brief Pain Inventory (BPI) at the Week 12 Double-Blind Endpoint
|
-3.0 units on a scale
Standard Deviation 2.16
|
-2.3 units on a scale
Standard Deviation 2.33
|
SECONDARY outcome
Timeframe: Double-blind Baseline and End of Double-Blind Treatment at 12 WeeksPopulation: Intent-to-treat (ITT) population. Last observation carried forward (LOCF) endpoint.
EQ-5D has 5 items (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) rated on a categorical scale of 1-3 with 1=no problems, 2=some problems, 3=extreme problems. The health state index is a weighted combination of the 5 items. It has a range of 0 to 1, with 0=deceased and 1=full health.
Outcome measures
| Measure |
DB Tapentadol ER
n=146 Participants
Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 12 weeks
|
DB Placebo
n=135 Participants
Double-Blind Placebo Control Group
|
|---|---|---|
|
Change From Baseline in the EuroQoL-5 Dimension (EQ-5D) Health Status Index at the Week 12 Endpoint
|
0.00 units on a scale
Standard Deviation 0.203
|
-0.10 units on a scale
Standard Deviation 0.257
|
Adverse Events
OL Tapentadol
Serious events: 11 serious events
Other events: 296 other events
Deaths: 0 deaths
DB Tapentadol ER
Serious events: 8 serious events
Other events: 86 other events
Deaths: 0 deaths
DB Placebo
Serious events: 9 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
OL Tapentadol
n=459 participants at risk
Tapentadol extended release (ER) 50 100 150 200 250 mg twice daily for 3 weeks
|
DB Tapentadol ER
n=166 participants at risk
Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 12 weeks
|
DB Placebo
n=152 participants at risk
Double-Blind Placebo Control Group
|
|---|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal Disorder
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/459
|
0.60%
1/166
|
0.66%
1/152
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/459
|
0.60%
1/166
|
0.66%
1/152
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Gastrointestinal disorders
Gastrointestinal Haemorrhage
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Infections and infestations
Diabetic Foot Infection
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Infections and infestations
Gastroenteritis Viral
|
0.22%
1/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Infections and infestations
Diverticulitis
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Infections and infestations
Localised Infection
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Infections and infestations
Necrotising Fasciitis
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Metabolism and nutrition disorders
Dehydration
|
0.44%
2/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Metabolism and nutrition disorders
Diabetes Mellitus Inadequate Control
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Vascular disorders
Arterial Stenosis Limb
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Vascular disorders
Hypotension
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Vascular disorders
Hypertension
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Cardiac disorders
Acute Coronary Syndrome
|
0.00%
0/459
|
0.60%
1/166
|
0.66%
1/152
|
|
Cardiac disorders
Angina Unstable
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Cardiac disorders
Atrial Fibrillation
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Cardiac disorders
Coronary Artery Disease
|
0.00%
0/459
|
0.00%
0/166
|
1.3%
2/152
|
|
Cardiac disorders
Coronary Artery Occlusion
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Cardiac disorders
Myocardial Ischaemia
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Nervous system disorders
Syncope
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Nervous system disorders
Balance Disorder
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Nervous system disorders
Dizziness
|
0.22%
1/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Nervous system disorders
Presyncope
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Nervous system disorders
Tremor
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Psychiatric disorders
Suicidal Ideation
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Skin and subcutaneous tissue disorders
Dry Gangrene
|
0.00%
0/459
|
0.60%
1/166
|
0.00%
0/152
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Eye disorders
Vision Blurred
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
General disorders
Chest Pain
|
0.65%
3/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Injury, poisoning and procedural complications
Contusion
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Injury, poisoning and procedural complications
Fall
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Injury, poisoning and procedural complications
Skull Fractured Base
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Injury, poisoning and procedural complications
Subdural Haematoma
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Injury, poisoning and procedural complications
Traumatic Brain Injury
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Investigations
Electrocardiogram Change
|
0.22%
1/459
|
0.00%
0/166
|
0.00%
0/152
|
|
Renal and urinary disorders
Urinary Retention
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Surgical and medical procedures
Coronary Arterial Stent Insertion
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
|
Surgical and medical procedures
Coronary Artery Bypass
|
0.00%
0/459
|
0.00%
0/166
|
0.66%
1/152
|
Other adverse events
| Measure |
OL Tapentadol
n=459 participants at risk
Tapentadol extended release (ER) 50 100 150 200 250 mg twice daily for 3 weeks
|
DB Tapentadol ER
n=166 participants at risk
Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 12 weeks
|
DB Placebo
n=152 participants at risk
Double-Blind Placebo Control Group
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
24.4%
112/459
|
20.5%
34/166
|
9.2%
14/152
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
46/459
|
12.0%
20/166
|
3.9%
6/152
|
|
Gastrointestinal disorders
Diarrhoea
|
5.2%
24/459
|
6.6%
11/166
|
6.6%
10/152
|
|
Gastrointestinal disorders
Constipation
|
11.8%
54/459
|
5.4%
9/166
|
0.00%
0/152
|
|
Gastrointestinal disorders
Dry Mouth
|
8.7%
40/459
|
4.8%
8/166
|
1.3%
2/152
|
|
Nervous system disorders
Dizziness
|
17.0%
78/459
|
7.2%
12/166
|
1.3%
2/152
|
|
Nervous system disorders
Somnolence
|
10.7%
49/459
|
6.0%
10/166
|
0.66%
1/152
|
|
Nervous system disorders
Headache
|
9.6%
44/459
|
2.4%
4/166
|
5.3%
8/152
|
|
Psychiatric disorders
Insomnia
|
3.1%
14/459
|
5.4%
9/166
|
2.6%
4/152
|
|
Psychiatric disorders
Anxiety
|
2.0%
9/459
|
4.2%
7/166
|
5.3%
8/152
|
|
General disorders
Fatigue
|
9.6%
44/459
|
7.2%
12/166
|
0.66%
1/152
|
|
Infections and infestations
Nasopharyngitis
|
1.1%
5/459
|
5.4%
9/166
|
2.6%
4/152
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.4%
34/459
|
3.6%
6/166
|
0.00%
0/152
|
Additional Information
Director, Clinical Leader
Janssen Research&Development
Phone: 609-730-6777
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER