Clinical trial NCT01041859: A Study to Evaluate the Efficacy, Safety, and Tolerability of Tapentadol ER Compared With Placebo in Patients With Chronic, Painful Diabetic Peripheral Neuropathy
Official title: A Randomized-Withdrawal, Placebo-Controlled, Study Evaluating the Efficacy, Safety, and Tolerability of Tapentadol Extended-Release (ER) in Subjects With Chronic, Painful Diabetic Peripheral Neuropathy (DPN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetic Peripheral Neuropathy
Keywords: Diabetic Peripheral Neuropathy
Painful
Polyneuropathy
Peripheral neuropathy
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
Collaborators: name: Grünenthal GmbH
First posted: 2010-01-01
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy, safety, and tolerability of orally administered tapentadol extended release (ER) at dosages of 100 to 250 mg twice daily compared with placebo in patients with moderate to severe pain due to chronic, painful diabetic peripheral neuropathy (DPN) who tolerated tapentadol (ER) and have an initial treatment effect (pain improvement) after a 3-week, open-label titration period.

Detailed description: This is a randomized-withdrawal (only patients that have an initial response to tapentadol are assigned to either tapentadol or placebo), placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability 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) an open-label (all people involved know the identity of the intervention) phase, including a 13-day screening period, a 5-day washout period (where patients are to stop taking their pain medication), a 3-day pre-titration pain-intensity evaluation period (where patients will record their pain intensity twice daily in the morning and evening), and a 3-week, open-label titration period (all patients receive tapentadol study drug), 2) a 12-week, double-blind (neither physician nor patient knows the name of the assigned drug) maintenance phase, and 3) a posttreatment phase of approximately 10 to 14 days. The study will evaluate the effectiveness of orally administered tapentadol ER versus placebo in reducing patients' pain intensity. The pain intensity will be assessed by comparing the baseline pain level to the level at week 12 of the maintenance phase. The total duration of study drug treatment for each patient will be approximately 15 weeks. Safety and tolerability will be evaluated by vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms (ECGs), standardized neurologic examinations, and monitoring of adverse events. Patients will be titrated on tapentadol ER from a starting dose of 50 mg twice daily to the patient's optimal dose ranging between 100 mg and 250 mg twice a day, or placebo. All doses of study medication will be taken orally with approximately 120 ml of water with or without food for a maximum timeframe of 15 weeks.

Eligibility criteria: Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* Significant history of pulmonary, gastrointestinal, endocrine, metabolic (except diabetes mellitus), neurological, psychiatric disorders (resulting in disorientation, memory impairment or inability to report accurately as in schizophrenia)
* 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

Primary outcomes:
measure: 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
timeFrame: Double-Blind Baseline and 12 weeks (Primary endpoint is the average pain intensity score during the last week of the maintenance period)
Secondary outcomes:
measure: 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
timeFrame: Open-label Baseline and End of Double-Blind Treatment at 15 Weeks (3 weeks open-label plus 12 weeks double-blind)
measure: Distribution of Patient Global Impression of Change at Week 12 Endpoint
timeFrame: End of Double-Blind Treatment at 12 Weeks
measure: Change From Baseline of Open-Label in the Pain Intensity Subscale of the Brief Pain Inventory (BPI) at the Week 12 Double-Blind Endpoint
timeFrame: Open-label Baseline and End of Double-Blind Treatment at 15 Weeks (3 weeks open-label plus 12 weeks double-blind)
measure: Change From Baseline in the EuroQoL-5 Dimension (EQ-5D) Health Status Index at the Week 12 Endpoint
timeFrame: Double-blind Baseline and End of Double-Blind Treatment at 12 Weeks
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Fresno
country: United States
state: California
city: Orange
country: United States
state: California
city: Redding
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Spring Valley
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Clearwater
country: United States
state: Florida
city: Hallandale Beach
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Ormond Beach
country: United States
state: Florida
city: St Petersburg
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
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state: Georgia
city: Marietta
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Eagle
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Avon
country: United States
state: Indiana
city: Evansville
country: United States
state: Indiana
city: Fishers
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state: Indiana
city: Prairie Village
country: United States
state: Kansas
city: Shreveport
country: United States
state: Louisiana
city: Owings Mills
country: United States
state: Maryland
city: Pasadena
country: United States
state: Maryland
city: Rockville
country: United States
state: Maryland
city: Brockton
country: United States
state: Massachusetts
city: Edina
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Cedarhurst
country: United States
state: New York
city: Flushing
country: United States
state: New York
city: Ny
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Valley Stream
country: United States
state: New York
city: Williamsville
country: United States
state: New York
city: Hickory
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Medford
country: United States
state: Oregon
city: Allentown
country: United States
state: Pennsylvania
city: Altoona
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: Anderson
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Bulverde
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Schertz
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Alexandria
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Virginia Beach
country: United States
state: Virginia
city: Calgary
country: Canada
state: Alberta
city: Kelowna
country: Canada
state: British Columbia
city: Barrie
country: Canada
state: Ontario
city: Hamilton
country: Canada
state: Ontario
city: Hawkesbury
country: Canada
state: Ontario
city: Sarnia
country: Canada
state: Ontario
city: Sudbury
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Dollard-Des-Ormeaux
country: Canada
state: Quebec
city: Laval
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Clinical Trial
role: STUDY_DIRECTOR
References: