Study of REN-1654 in Patients With Sciatica Pain

Sciatica Clinical Trial

Official title:

REN-1654 in Sciatica: A Phase 2, Randomized, Double-Blind, Placebo Controlled, Multi-Center Study in Subjects With Pain Due to Lumbosacral Radiculopathy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00107055
• Other study ID #: REN-1654-2-03
• Status: Active, not recruiting
• Phase: Phase 2
• First received: April 4, 2005
• Last updated: June 23, 2005
• Start date: December 2003
• Est. completion date: April 2005

Study information

• Verified date: June 2005
• Source: Renovis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to gain initial safety and efficacy data on the experimental agent REN-1654 in patients with pain that radiates down the leg(s), and is typical of sciatica (lumbosacral radiculopathy). These patients will usually have a herniated disc that is causing compression on the nerves coming out of the spinal column.

Description:

This is a multi-center, randomized, double-blind, placebo-controlled study to determine the efficacy and tolerability of REN-1654 in subjects with sciatica. After screening and baseline clinical assessments, subjects will be randomly assigned to receive REN 1654 100 mg or matching placebo, once daily for 3 weeks. Leg pain, back pain and other efficacy measures will be assessed at 1 and 3 weeks after initiation of treatment. A subset of patients will undergo analysis of blood levels of REN-1654 during the course of the study (pharmacokinetics). Subjects will discontinue treatment after 3 weeks and return after a further 3 weeks off therapy for a final clinical assessment 6 weeks after initiation of treatment. If a subject does not return for follow-up, an effort will be made by telephone to document their clinical status and whether other interventions have been made.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 72
• Est. completion date: April 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Males or females, ages 18 to 55, able and willing to provide written informed consent to participate in the study.

• Able to read, understand and follow the study instructions, including completion of pain intensity rating scales.

• Leg pain radiating to or below the knee in a dermatomal pattern, diagnosed as being due to sciatica or lumbar or lumbosacral radiculopathy, the onset of which occurred 2 to 12 weeks prior to initiation of study treatment.

• Leg pain severity on a screening Categorical Pain Intensity Rating (for the prior 24 hour period) of at least 4, using an 11-point categorical pain intensity scale with 0 = no pain and 10 = worst pain imaginable.

• Leg pain on a screening Categorical Pain Intensity Rating rated as more severe than back pain.

• Positive straight leg raising (SLR) test as defined in Appendix B of this protocol.

• Subjects who are compliant in maintaining a Pain Diary between screening and baseline visits, and who record a 24-hour average Categorical Pain Intensity Rating score of at least 4 or greater on at least 3 days during the week prior to baseline visit.

• Subject who can maintain stable pharmacologic treatments for sciatica symptoms taken prior to dosing including analgesics, anti-inflammatory medications (e.g. NSAIDS), antidepressants, anticonvulsants, anxiolytics, or muscle relaxants. Subjects must be on stable doses of such medications for 2 weeks prior to the baseline visit, and maintained on the same doses throughout the study. Medications taken on an as-needed basis are permitted, and subjects will be asked to record daily usage of such medications in the subject diary.

• Subjects who at screening are receiving adjunctive analgesic therapy such as acupuncture or biofeedback should either discontinue it or establish a schedule of treatments that will remain consistent for 2 weeks prior to the baseline visit, and throughout the study.

• Subject with screening laboratory values within normal limits, or if abnormal must be considered not clinically significant and in the opinion of the Investigator not to place the subjects at risk.

• If female, must be post-menopausal, surgically sterile, not currently pregnant (verified by a screening pregnancy test) or nursing, and using a reliable contraception method such as intrauterine device (IUD), hormonal birth control pills, or double barrier method (male condom, female condom or diaphragm with spermicidal jelly).

• If male, must agree to use double-barrier methods of contraception.

Exclusion Criteria:

• History of peripheral neuropathy or any other pain conditions with pain intensity equal to or greater than the pain associated with sciatica.

• Motor loss in a muscle corresponding to the affected dermatome graded as more than “trace”.

• History of cauda equina syndrome, symptomatic scoliosis, spondylolisthesis (degenerative or isthmic), ankylosing spondylitis, rheumatoid arthritis or other inflammatory arthropathies. Degenerative arthritis is allowed.

• History of hepatic, cardiovascular, renal, gastrointestinal, hematological, neurological, endocrine (including diabetes), metabolic, pulmonary, immunological (including HIV infection) or psychiatric disease that in the opinion of the Investigator would pose a significant safety risk for a subject exposed to an investigational compound such as REN-1654.

• History of the following ophthalmic disorders based upon general medical review at the screening visit. Subjects will further undergo a screening ophthalmologic assessment. Should any of the following be identified at the screening ophthalmologic examination, the subject will be excluded from the study.

• Symptomatic cataract, resulting in any visual impairment (if a subject has been diagnosed with cataract to a degree that the cataract interferes with daily living and/or regarding which an ophthalmologist has recommended cataract surgery);

• Other vision-impairing disorders (if a subject is aware of any eye disorder that has impaired vision, such as age-related macular degeneration, lazy eye (amblyopia), double vision, or any optic nerve inflammation; presbyopia and other non-pathological visual acuity deficits are not exclusionary);

• Glaucoma or history of ocular hypertension (intraocular pressures greater than 21 mmHg).

• Cognitive or psychiatric disorders that may diminish compliance with study procedures, including maintenance of a daily pain diary and accurate dosing of study medication.

• Subjects who, at time of enrollment, have requested for or been advised by their physicians to receive local, regional, or spinal (articular, epidural, intrathecal or nerve root block) injections of medications for pain treatment or surgical intervention for their sciatica symptoms.

• Although subjects who report work-related injuries will be allowed to enroll, subjects will be excluded if they are involved in litigation related to the current episode of sciatica.

• Subjects with a screening creatinine laboratory value of = 2.0 mg/dL.

• Screening liver enzyme results greater than the upper limit of the normal range

• Use of chemotherapy agents or history of cancer, other than basal cell carcinoma and squamous cell carcinoma, within five years prior to the screening visit.

• History of drug or alcohol abuse within one year prior to screening.

• Use within 2 weeks before start of study investigational compound dosing at baseline and through the end of the study of any investigational compound, any epidural, intrathecal, or nerve root block agent, corticosteroids, etanercept or other anti-TNF-a agent, topical anesthetics, or topical analgesics .

• Previous participation in another REN-1654 study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Educational/Counseling/Training

Related Conditions & MeSH terms

• Herniated Disc
• Radiculopathy
• Sciatica

Intervention

Drug:
• REN-1654

Locations

Country	Name	City	State
United States	Lehigh Valley Hospital Neurosciences and Pain Research	Allentown	Pennsylvania
United States	Asheville Neurology Specialists, PA	Asheville	North Carolina
United States	Emory Orthopaedics and Spine Center	Atlanta	Georgia
United States	Central Texas Spine Institute	Austin	Texas
United States	Alabama Clinical Therapeutics	Birmingham	Alabama
United States	Brigham & Women's Hospital, Pain Trials Center	Boston	Massachusetts
United States	Clinical Research of West Florida	Clearwater	Florida
United States	The Cleveland Clinic Spine Institute	Cleveland	Ohio
United States	Mile High Research Center	Denver	Colorado
United States	Research Across America	New York	New York
United States	Renstar Medical Research, Inc.	Ocala	Florida
United States	Wake Research Associates	Raleigh	North Carolina
United States	A&A Pain Institute of St. Louis	St. Louis	Missouri
United States	Washington University School of Medicine, Pain Management Center	St. Louis	Missouri
United States	Suncoast Neuroscience Associates	St. Petersburg	Florida
United States	Orthopaedic Spine Center at Stanford University Medical Center	Stanford	California
United States	Advanced Clinical Therapeutics, LLC	Tuscon	Arizona
United States	Omega Medical Research	Warwick	Rhode Island
United States	Advanced Clinical Research	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Renovis

Country where clinical trial is conducted

United States, 

References & Publications (2)

Karppinen J, Korhonen T, Malmivaara A, Paimela L, Kyllönen E, Lindgren KA, Rantanen P, Tervonen O, Niinimäki J, Seitsalo S, Hurri H. Tumor necrosis factor-alpha monoclonal antibody, infliximab, used to manage severe sciatica. Spine (Phila Pa 1976). 2003 Apr 15;28(8):750-3; discussion 753-4. — View Citation

Sommer C, Schäfers M, Marziniak M, Toyka KV. Etanercept reduces hyperalgesia in experimental painful neuropathy. J Peripher Nerv Syst. 2001 Jun;6(2):67-72. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Leg Pain: Change in Average Daily 11-Point Categorical Pain Intensity Rating at the end of the 3-week treatment period
Secondary	Initiation of the following clinical interventions and time to intervention, if elected, through the 3-week treatment period and 3-week post treatment follow-up period:
Secondary	[1] Local, regional, or spinal (articular, epidural, intrathecal, or nerve root block) injections of medications for pain treatment. [2] Surgery for treatment of sciatica symptoms
Secondary	Use of concomitant analgesic medications (tracked by daily log of medication usage)
Secondary	Back Pain: Change in Average Daily Categorical Pain Intensity
Secondary	Leg Pain: Change in Maximum (or movement-induced) Daily Categorical Pain Intensity Rating
Secondary	Back Pain: Change in Maximum (or movement-induced) Daily Categorical Pain Intensity
Secondary	Change in Oswestry Low Back Disability Questionnaire; Change in Straight Leg Raising test
Secondary	Change in muscle weakness
Secondary	Change in sensory deficit
Secondary	Change in tendon reflexes
Secondary	Global impression of change: subject and investigator