Efficacy and Safety of SAR292833 Administration for 4 Weeks in Patients With Chronic Peripheral Neuropathic Pain

Neuropathic Pain Clinical Trial

— Alchemilla  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01463397
• Other study ID #: ACT11917
• Secondary ID: 2011-001876-21U1
• Status: Completed
• Phase: Phase 2
• First received: October 28, 2011
• Last updated: January 28, 2016
• Start date: March 2012
• Est. completion date: May 2013

Study information

• Verified date: January 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 191
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain

Intervention

Drug:
• SAR292833
Pharmaceutical form: capsule Route of administration: oral
• placebo
Pharmaceutical form:capsule Route of administration: oral

Locations

Country	Name	City	State
Czech Republic	Investigational Site Number 203002	Olomouc
Czech Republic	Investigational Site Number 203005	Praha 10
Czech Republic	Investigational Site Number 203006	Praha 10
Hungary	Investigational Site Number 348001	Budapest
Hungary	Investigational Site Number 348002	Budapest
Hungary	Investigational Site Number 348005	Budapest
Hungary	Investigational Site Number 348007	Budapest
Hungary	Investigational Site Number 348006	Debrecen
Hungary	Investigational Site Number 348003	Zalaegerszeg
Poland	Investigational Site Number 616001	Bydgoszcz
Poland	Investigational Site Number 616002	Lublin
Poland	Investigational Site Number 616007	Sandomierz
Poland	Investigational Site Number 616004	Wloclawek
Russian Federation	Investigational Site Number 643006	Kazan
Russian Federation	Investigational Site Number 643007	Kazan
Russian Federation	Investigational Site Number 643001	Moscow
Russian Federation	Investigational Site Number 643008	Moscow
Russian Federation	Investigational Site Number 643009	Moscow
Russian Federation	Investigational Site Number 643010	Moscow
Russian Federation	Investigational Site Number 643011	Moscow
Russian Federation	Investigational Site Number 643004	Nizhny Novgorod
Russian Federation	Investigational Site Number 643012	Novosibirsk
Russian Federation	Investigational Site Number 643003	St-Petersburg
Russian Federation	Investigational Site Number 643013	St-Petersburg
Russian Federation	Investigational Site Number 643014	St-Petersburg
Russian Federation	Investigational Site Number 643005	Yaroslavl
Slovakia	Investigational Site Number 703004	Banska Bystrica
Slovakia	Investigational Site Number 703001	Dubnica Nad Vahom
Slovakia	Investigational Site Number 703003	Krompachy
Ukraine	Investigational Site Number 804002	Kiev
Ukraine	Investigational Site Number 804005	Kiev
Ukraine	Investigational Site Number 804003	Kyiv
Ukraine	Investigational Site Number 804004	Kyiv
United States	Investigational Site Number 840037	Albuquerque	New Mexico
United States	Investigational Site Number 840044	Altoona	Pennsylvania
United States	Investigational Site Number 840006	Austin	Texas
United States	Investigational Site Number 840046	Coral Gables	Florida
United States	Investigational Site Number 840032	Dallas	Texas
United States	Investigational Site Number 840043	Dallas	Texas
United States	Investigational Site Number 840019	Evansville	Indiana
United States	Investigational Site Number 840042	Framingham	Massachusetts
United States	Investigational Site Number 840007	Garden Grove	California
United States	Investigational Site Number 840040	Hartsdale	New York
United States	Investigational Site Number 840012	Indianapolis	Indiana
United States	Investigational Site Number 840018	Johnstown	Pennsylvania
United States	Investigational Site Number 840010	Las Vegas	Nevada
United States	Investigational Site Number 840001	New York	New York
United States	Investigational Site Number 840020	Newport Beach	California
United States	Investigational Site Number 840013	Ocala	Florida
United States	Investigational Site Number 840034	Palm Beach Gardens	Florida
United States	Investigational Site Number 840015	Raleigh	North Carolina
United States	Investigational Site Number 840033	Rochester	New York
United States	Investigational Site Number 840038	Santa Ana	California
United States	Investigational Site Number 840016	Seattle	Washington
United States	Investigational Site Number 840004	Springfield	Massachusetts
United States	Investigational Site Number 840035	St. Louis	Missouri
United States	Investigational Site Number 840017	Toledo	Ohio
United States	Investigational Site Number 840014	Tucson	Arizona
United States	Investigational Site Number 840045	Tullahoma	Tennessee
United States	Investigational Site Number 840002	Tustin	California
United States	Investigational Site Number 840022	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Czech Republic,  Hungary,  Poland,  Russian Federation,  Slovakia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in the average daily pain intensity as measured by the 11-point NRS;	The average daily pain intensity is the mean of the last consecutive 7 days.	Baseline to 4 weeks	No
Secondary	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;		Baseline to 4 weeks	No
Secondary	Change in Neuropathic Pain Symptom Inventory (NPSI) after 4 weeks treatment compared to baseline		Baseline to 4 weeks	No
Secondary	Change in intensity of the mechanical allodynia after 4 weeks treatment compared to baseline using visual analog scale (VAS)		Baseline to 4 weeks	No
Secondary	Amount of and time to first rescue medication intake during the treatment period.		4 weeks	No
Secondary	Change in Daily Sleep Interference Score (DSIS), clinical global impression of change (PGIC and CGIC).		4 weeks	No