Clinical trial NCT01463397: Efficacy and Safety of SAR292833 Administration for 4 Weeks in Patients With Chronic Peripheral Neuropathic Pain
Official title: Multinational, Multicenter, Randomized Double-Blind, Placebo-Controlled, Parallel-Group Study of Efficacy and Safety of SAR292833 Administration for 4 Weeks in Patients With Chronic Peripheral Neuropathic Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuropathic Pain
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-11-01
Enrollment: 191
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To assess the efficacy of SAR292833 versus placebo in reducing pain intensity associated with chronic peripheral neuropathic pain using 11-point numerical rating scale (NRS).

Secondary Objectives:

* To compare the effects of SAR292833 with placebo on the change of neuropathic pain symptoms versus baseline Neuropathic Pain Symptoms Inventory (NPSI);
* To evaluate the effects of SAR292833 in comparison to placebo on the change in pain intensity of mechanical allodynia;
* To investigate the safety and tolerability of SAR292833 in comparison to placebo;
* To investigate the pharmacokinetics (PK) and the relationships between main efficacy parameters or pharmacodynamic effect (PD) and pharmacokinetics (PK/PD) of SAR292833 in patients with chronic peripheral neuropathic pain.

Detailed description: Total study duration (from screening to last follow-up visit) is 9 weeks that includes a 3 week follow-up period.

Eligibility criteria: Inclusion criteria:

-The study will include adult patients of either gender, 18 - 85 of age, who have signed the informed consent form, and presenting with chronic peripheral neuropathic pain associated with: diabetic polyneuropathy, post-herpetic neuralgia.

* The neuropathic pain must have a distinct neuroanatomically plausible distribution with sensory signs and symptoms confirmed by DN4 (Douleur Neuropathique en 4 questions) score of ≥4 and being present for more than 3 months.
* SAR292833 should be taken in fed condition. Therefore, only patients who were judged to be reliable to fulfill this condition (used to having breakfast and dinner) will be included in the study.

Exclusion criteria:

* Patients with a baseline average daily pain intensity for their neuropathic pain \< 5 on the 11-point NRS over the last 7 days before randomization;
* Patients with a pain intensity of ≥ 9 on the 11-point NRS at Visit 1;
* Any pain other than the neuropathic pain of equal or greater severity;
* Sensory polyneuropathy post chemotherapy or in the context of cancer or AIDS;
* Patients with complex regional pain syndrome;
* Trigeminal neuralgia;
* Patients with clinically significant or uncontrolled hepatic, metabolic, gastrointestinal, cardiovascular, respiratory, neurological (other than neuropathy), psychiatric, hematological, renal, or dermatological disease, or any other medical condition that might interfere with the evaluation of study medication according to Investigator's medical judgment;
* Patients on statins metabolized by CYP3A4, (e.g. simvastatin, atorvastatin) and abnormal CPK level;
* Major depression;
* Serum creatinine \>150 μmol/L;
* ALT 3 x ULN;
* Total bilirubin \> 1.5 x ULN except known Gilbert syndrome;
* Presence of signs of clinically significant abnormalities on a standard electrocardiogram (ECG) recording at the screening visit according to Investigator's medical judgment;
* Pregnant or breastfeeding women;
* Women of childbearing potential (WOCBP), not protected by highly effective contraceptive method of birth control;
* Patients with diabetes mellitus and time between diagnosis of diabetes and enrolment \<6 months;
* Patients with diabetes mellitus and HbA1c \>10% or fasting plasma glucose \>250 mg/dL;
* Use of the following drugs within 7 days prior to start with the pain intensity assessment (Visit 2):
* Antidepressants (except for stable \[\>30 days\] regimens of Selective serotonin reuptake inhibitors (SSRIs) for treatment of anxiety or depression), anticonvulsants or mexiletine for the treatment of pain;
* Opioids or morphinomimetics;
* Fatty acid supplements, primrose oil, myoinositol, chromium picolinate that are known to be used in neuropathic pain;
* Acetyl salicylic acid (ASA) except up to 325 mg/d for myocardial infarction or transient ischemic attack prophylaxis;
* Benzodiazepines other than indicated at low doses for sleep disorders;
* Capsaicin patch;
* Lidocaine patch;
* Electroconvulsive therapy within 30 days of baseline evaluation;
* CYP3A4 potent and moderate inhibitors;
* CYP3A4 potent and moderate inducers;
* Substrates of CYP3A4 with narrow therapeutic window.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Change from baseline in the average daily pain intensity as measured by the 11-point NRS;
timeFrame: Baseline to 4 weeks
Secondary outcomes:
measure: Percentage of patients with reduction in pain intensity of at least 30% and 50% at endpoint compared to baseline derived from the primary efficacy endpoint;
timeFrame: Baseline to 4 weeks
measure: Change in Neuropathic Pain Symptom Inventory (NPSI) after 4 weeks treatment compared to baseline
timeFrame: Baseline to 4 weeks
measure: Change in intensity of the mechanical allodynia after 4 weeks treatment compared to baseline using visual analog scale (VAS)
timeFrame: Baseline to 4 weeks
measure: Amount of and time to first rescue medication intake during the treatment period.
timeFrame: 4 weeks
measure: Change in Daily Sleep Interference Score (DSIS), clinical global impression of change (PGIC and CGIC).
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Investigational Site Number 840014
state: Arizona
city: Garden Grove
country: United States
facility: Investigational Site Number 840007
state: California
city: Newport Beach
country: United States
facility: Investigational Site Number 840020
state: California
city: Santa Ana
country: United States
facility: Investigational Site Number 840038
state: California
city: Tustin
country: United States
facility: Investigational Site Number 840002
state: California
city: Coral Gables
country: United States
facility: Investigational Site Number 840046
state: Florida
city: Ocala
country: United States
facility: Investigational Site Number 840013
state: Florida
city: Palm Beach Gardens
country: United States
facility: Investigational Site Number 840034
state: Florida
city: Evansville
country: United States
facility: Investigational Site Number 840019
state: Indiana
city: Indianapolis
country: United States
facility: Investigational Site Number 840012
state: Indiana
city: Framingham
country: United States
facility: Investigational Site Number 840042
state: Massachusetts
city: Springfield
country: United States
facility: Investigational Site Number 840004
state: Massachusetts
city: St. Louis
country: United States
facility: Investigational Site Number 840035
state: Missouri
city: Las Vegas
country: United States
facility: Investigational Site Number 840010
state: Nevada
city: Albuquerque
country: United States
facility: Investigational Site Number 840037
state: New Mexico
city: Hartsdale
country: United States
facility: Investigational Site Number 840040
state: New York
city: New York
country: United States
facility: Investigational Site Number 840001
state: New York
city: Rochester
country: United States
facility: Investigational Site Number 840033
state: New York
city: Raleigh
country: United States
facility: Investigational Site Number 840015
state: North Carolina
city: Winston Salem
country: United States
facility: Investigational Site Number 840022
state: North Carolina
city: Toledo
country: United States
facility: Investigational Site Number 840017
state: Ohio
city: Altoona
country: United States
facility: Investigational Site Number 840044
state: Pennsylvania
city: Johnstown
country: United States
facility: Investigational Site Number 840018
state: Pennsylvania
city: Tullahoma
country: United States
facility: Investigational Site Number 840045
state: Tennessee
city: Austin
country: United States
facility: Investigational Site Number 840006
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840043
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 840032
state: Texas
city: Seattle
country: United States
facility: Investigational Site Number 840016
state: Washington
city: Olomouc
country: Czech Republic
facility: Investigational Site Number 203002
city: Praha 10
country: Czech Republic
facility: Investigational Site Number 203005
city: Praha 10
country: Czech Republic
facility: Investigational Site Number 203006
city: Budapest
country: Hungary
facility: Investigational Site Number 348001
city: Budapest
country: Hungary
facility: Investigational Site Number 348005
city: Budapest
country: Hungary
facility: Investigational Site Number 348007
city: Budapest
country: Hungary
facility: Investigational Site Number 348002
city: Debrecen
country: Hungary
facility: Investigational Site Number 348006
city: Zalaegerszeg
country: Hungary
facility: Investigational Site Number 348003
city: Bydgoszcz
country: Poland
facility: Investigational Site Number 616001
city: Lublin
country: Poland
facility: Investigational Site Number 616002
city: Sandomierz
country: Poland
facility: Investigational Site Number 616007
city: Wloclawek
country: Poland
facility: Investigational Site Number 616004
city: Kazan
country: Russian Federation
facility: Investigational Site Number 643006
city: Kazan
country: Russian Federation
facility: Investigational Site Number 643007
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643008
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643010
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643009
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643011
city: Nizhny Novgorod
country: Russian Federation
facility: Investigational Site Number 643004
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number 643012
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643013
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643003
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643014
city: Yaroslavl
country: Russian Federation
facility: Investigational Site Number 643005
city: Banska Bystrica
country: Slovakia
facility: Investigational Site Number 703004
city: Dubnica Nad Vahom
country: Slovakia
facility: Investigational Site Number 703001
city: Krompachy
country: Slovakia
facility: Investigational Site Number 703003
city: Kiev
country: Ukraine
facility: Investigational Site Number 804002
city: Kiev
country: Ukraine
facility: Investigational Site Number 804005
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804004
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: