A Long-term Safety Study With Tapentadol ER and Oxycodone CR in Patients With Moderate to Severe Pain Due to Chronic, Painful Diabetic Peripheral Neuropathy (DPN)
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety profile of orally administered tapentadol ER dosages of 100 to 250 mg twice daily in patients with chronic, painful diabetic peripheral neuropathy (DPN) over long-term exposure of up to 1 year.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a randomized, open-label, active-controlled, multicenter study evaluating the safety profile of orally administered tapentadol, using the extended release tamper-resistant formulation (TRF), at dosages of 100 to 250 mg twice daily in patients with moderate to severe pain due to chronic, painful DPN. The study consists of 1) a 13-day screening period, a 3-7-day washout period (where patients are to stop taking their pain medication), a 1-day pretitration pain-intensity evaluation period (where patients will record their 24-hour pain intensity), and a 3-week, open-label titration period (patients will receive either tapentadol ER or oxycodone CR study drug in a 3 to 1 ratio), 2) a 49-week, open-label maintenance phase, and 3) a posttreatment phase of approximately 10 to 14 days. The study will evaluate the safety and tolerability of orally administered tapentadol ER by vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms (ECGs), opioid withdrawal scales, assessment of patient-reported constipation, standardized neurologic examinations and monitoring of adverse events. Assessments of pain relief include the pain intensity numerical rating scale, and patient global impression of change scale (PGIC). The total duration of study drug treatment for each patient will be approximately 52 weeks. Titrate tapentadol ER 50 mg twice daily or oxycodone CR 10 mg twice daily to patient's optimal dose ranging between 100 mg and 250 mg twice daily or 20 and 50 mg twice daily, respectively. All doses of study medication will be taken orally with or without food for a maximum timeframe of 52 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 001 Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 52 weeks |
Drug: Tapentadol extended release (ER)
100, 150, 200, 250 mg twice daily for 52 weeks
|
| Active Comparator: 002 Oxycodone controlled release (CR) 20 30 40 50 mg twice daily for 52 weeks |
Drug: Oxycodone controlled release (CR)
20, 30, 40, 50 mg twice daily for 52 weeks
|
Outcome Measures
Primary Outcome Measures
- Number of Subjects With Treatment-emergent Adverse Events (TEAE) [Entire Study]
The number of participants who reported a TEAE during the treatment period. TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 3 days after the discontinuation of the study medication.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Man or woman aged 18 years or older
-
Patients with Type 1 or 2 diabetes mellitus must have a documented clinical diagnosis of painful diabetic peripheral neuropathy with symptoms and signs for at least 6 months, and pain present at the time of screening
-
Diagnosis must include pain plus reduction or absence of pin sensibility and/or vibration sensibility on Total Neuropathy Score - Nurse (TNSn) examination in lower and/or upper extremities at screening
-
The investigator considers the patient's blood glucose to be controlled by diet, or hypoglycemics, or insulin for at least 3 months prior to enrolling in the study (this control should be documented by figures of glycated hemoglobin (HbA1c) no greater than 11% at screening)
-
Patients have been taking analgesic medications for the condition for at least 3 months prior to screening (patients taking opioid analgesics must be dissatisfied with current treatment, and patients taking non-opioid analgesics must be dissatisfied with current analgesia)
-
Patients currently requiring opioid treatment must be taking daily doses of an opioid-based analgesic equivalent to <=160mg of oral morphine
-
Patients with baseline score for average pain intensity in the previous 24 hours of =>4 on the 11-point numerical rating scale (NRS) at the beginning of the titration period
Exclusion Criteria:
-
Significant pulmonary, gastrointestinal, endocrine, metabolic (except diabetes mellitus), neurological, psychiatric disorders (resulting in disorientation, memory impairment or inability to report accurately as in schizophrenia, Alzheimer's disease)
-
History of moderate to severe hepatic impairment
-
Severely impaired renal function
-
Clinically significant laboratory abnormalities
-
Clinically significant cardiac disease
-
History of seizure disorder or epilepsy
-
History of any other clinically significant disease that in the investigator's opinion may affect efficacy or safety assessments or may compromise patient safety during study participation.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mesa | Arizona | United States | ||
| 2 | Tucson | Arizona | United States | ||
| 3 | Fruitland Park | Florida | United States | ||
| 4 | New Port Richey | Florida | United States | ||
| 5 | Oviedo | Florida | United States | ||
| 6 | Tampa | Florida | United States | ||
| 7 | Libertyville | Illinois | United States | ||
| 8 | Franklin | Indiana | United States | ||
| 9 | Paducah | Kentucky | United States | ||
| 10 | Wellesley Hills | Massachusetts | United States | ||
| 11 | Albuquerque | New Mexico | United States | ||
| 12 | New York | New York | United States | ||
| 13 | Greenville | North Carolina | United States | ||
| 14 | Hickory | North Carolina | United States | ||
| 15 | Wilmington | North Carolina | United States | ||
| 16 | Winston Salem | North Carolina | United States | ||
| 17 | Kettering | Ohio | United States | ||
| 18 | Tulsa | Oklahoma | United States | ||
| 19 | Greer | South Carolina | United States | ||
| 20 | Dallas | Texas | United States | ||
| 21 | Odessa | Texas | United States | ||
| 22 | San Antonio | Texas | United States | ||
| 23 | Virginia Beach | Virginia | United States |
Sponsors and Collaborators
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Grünenthal GmbH
Investigators
- Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR016978
- R331333PAI3028
- KF57
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Tapentadol ER | Oxycodone CR |
|---|---|---|
| Arm/Group Description | Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 52 weeks | Oxycodone controlled release (CR) 20 30 40 50 mg twice daily for 52 weeks |
| Period Title: Overall Study | ||
| STARTED | 35 | 12 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 35 | 12 |
Baseline Characteristics
| Arm/Group Title | Tapentadol ER | Oxycodone CR | Total |
|---|---|---|---|
| Arm/Group Description | Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 52 weeks | Oxycodone controlled release (CR) 20 30 40 50 mg twice daily for 52 weeks | Total of all reporting groups |
| Overall Participants | 35 | 12 | 47 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
26
74.3%
|
9
75%
|
35
74.5%
|
| >=65 years |
9
25.7%
|
3
25%
|
12
25.5%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
57.5
(12.41)
|
60.1
(9.23)
|
58.2
(11.64)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
15
42.9%
|
2
16.7%
|
17
36.2%
|
| Male |
20
57.1%
|
10
83.3%
|
30
63.8%
|
| Region Enroll (United States of America) (participants) [Number] | |||
| Number [participants] |
35
100%
|
12
100%
|
47
100%
|
Outcome Measures
| Title | Number of Subjects With Treatment-emergent Adverse Events (TEAE) |
|---|---|
| Description | The number of participants who reported a TEAE during the treatment period. TEAE was defined as any adverse event that started or worsened on or after the start of the study medication and up to 3 days after the discontinuation of the study medication. |
| Time Frame | Entire Study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set (All randomized participants who took at least one dose of study medication). |
| Arm/Group Title | Tapentadol ER | Oxycodone CR |
|---|---|---|
| Arm/Group Description | Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 52 weeks | Oxycodone controlled release (CR) 20 30 40 50 mg twice daily for 52 weeks |
| Measure Participants | 35 | 12 |
| Number [participants] |
23
65.7%
|
11
91.7%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | Only participants who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total number of participants with Non-Serious Adverse Events. | |||
| Arm/Group Title | Tapentadol ER | Oxycodone CR | ||
| Arm/Group Description | Tapentadol extended release (ER) 100 150 200 250 mg twice daily for 52 weeks | Oxycodone controlled release (CR) 20 30 40 50 mg twice daily for 52 weeks | ||
All Cause Mortality |
||||
| Tapentadol ER | Oxycodone CR | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Tapentadol ER | Oxycodone CR | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/35 (0%) | 0/12 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Tapentadol ER | Oxycodone CR | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/35 (54.3%) | 11/12 (91.7%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 7/35 (20%) | 6/12 (50%) | ||
| Dry mouth | 3/35 (8.6%) | 1/12 (8.3%) | ||
| Constipation | 2/35 (5.7%) | 3/12 (25%) | ||
| Diarrhoea | 2/35 (5.7%) | 0/12 (0%) | ||
| Vomiting | 1/35 (2.9%) | 2/12 (16.7%) | ||
| Abdominal pain | 0/35 (0%) | 2/12 (16.7%) | ||
| General disorders | ||||
| Fatigue | 3/35 (8.6%) | 2/12 (16.7%) | ||
| Asthenia | 0/35 (0%) | 1/12 (8.3%) | ||
| Infections and infestations | ||||
| Upper respiratory tract infection | 2/35 (5.7%) | 0/12 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 1/35 (2.9%) | 1/12 (8.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 2/35 (5.7%) | 0/12 (0%) | ||
| Back pain | 1/35 (2.9%) | 1/12 (8.3%) | ||
| Myalgia | 0/35 (0%) | 1/12 (8.3%) | ||
| Nervous system disorders | ||||
| Somnolence | 3/35 (8.6%) | 3/12 (25%) | ||
| Dizziness | 1/35 (2.9%) | 1/12 (8.3%) | ||
| Headache | 1/35 (2.9%) | 3/12 (25%) | ||
| Psychiatric disorders | ||||
| Anxiety | 2/35 (5.7%) | 1/12 (8.3%) | ||
| Confusional state | 2/35 (5.7%) | 0/12 (0%) | ||
| Insomnia | 2/35 (5.7%) | 0/12 (0%) | ||
| Abnormal dreams | 0/35 (0%) | 1/12 (8.3%) | ||
| Depression | 0/35 (0%) | 1/12 (8.3%) | ||
| Euphoric mood | 0/35 (0%) | 1/12 (8.3%) | ||
| Mood swings | 0/35 (0%) | 1/12 (8.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 2/35 (5.7%) | 3/12 (25%) | ||
| Hyperhidrosis | 1/35 (2.9%) | 1/12 (8.3%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Senior Director, Clinical Leader |
|---|---|
| Organization | Johnson & Johnson Pharmaceutical Research & Development, L.L.C. |
| Phone | 609-730-4537 |
- CR016978
- R331333PAI3028
- KF57