Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) in the Treatment of Major Depressive Disorder

June 8, 2011 updated by: Pfizer

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of 2 Fixed Doses (25 and 50 mg/Day) of DVS SR Tablets in Adult Outpatients With Major Depressive Disorder

The primary purpose of this study is to compare the antidepressant efficacy and safety of two doses of DVS SR (25 and 50 mg/day) in the treatment of adults with Major Depressive Disorder. The study will also assess changes in sexual function and general and functional quality of life outcomes.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
709

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Fukuoka, Japan, 8100001
        • Pfizer Investigational Site
      • Fukuoka, Japan, 8100041
        • Pfizer Investigational Site
      • Fukushima, Japan, 9600102
        • Pfizer Investigational Site
      • Hiroshima, Japan, 7310121
        • Pfizer Investigational Site
      • Kumamoto, Japan, 8618002
        • Pfizer Investigational Site
      • Kumamoto, Japan, 8620909
        • Pfizer Investigational Site
      • Kyoto, Japan, 6168421
        • Pfizer Investigational Site
      • Osaka, Japan, 5420006
        • Pfizer Investigational Site
      • Saitama, Japan, 33000062
        • Pfizer Investigational Site
      • Saitama, Japan, 3390057
        • Pfizer Investigational Site
    • Aichi
      • Nagoya, Aichi, Japan, 4530015
        • Pfizer Investigational Site
      • Toyoake, Aichi, Japan, 4701192
        • Pfizer Investigational Site
    • Chiba
      • Noda, Chiba, Japan, 2780033
        • Pfizer Investigational Site
    • Fukuoka
      • Kitakyusyu, Fukuoka, Japan, 8020006
        • Pfizer Investigational Site
      • Kitakyusyu, Fukuoka, Japan, 8078555
        • Pfizer Investigational Site
    • Fukushima
      • Shirakawa, Fukushima, Japan, 9610021
        • Pfizer Investigational Site
    • Gunma
      • Fujioka, Gunma, Japan, 3750017
        • Pfizer Investigational Site
      • Kumagaya, Gunma, Japan, 3600032
        • Pfizer Investigational Site
    • Hiroshima
      • Hatsukaichi, Hiroshima, Japan, 7380023
        • Pfizer Investigational Site
      • Kure, Hiroshima, Japan, 7370023
        • Pfizer Investigational Site
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 0028029
        • Pfizer Investigational Site
      • Sapporo, Hokkaido, Japan, 0040052
        • Pfizer Investigational Site
      • Sapporo, Hokkaido, Japan, 0600061
        • Pfizer Investigational Site
      • Sapporo, Hokkaido, Japan, 600042
        • Pfizer Investigational Site
      • Sapporo, Hokkaido, Japan, 630061
        • Pfizer Investigational Site
      • Sapporo, Hokkaido, Japan, 630804
        • Pfizer Investigational Site
    • Hyogo
      • Kobe, Hyogo, Japan, 6530841
        • Pfizer Investigational Site
    • Ishikawa
      • Kanazawa, Ishikawa, Japan, 9208650
        • Pfizer Investigational Site
    • Kanagawa
      • Minamiashigara, Kanagawa, Japan, 2500136
        • Pfizer Investigational Site
      • Yokohama, Kanagawa, Japan, 2200004
        • Pfizer Investigational Site
      • Yokohama, Kanagawa, Japan, 2210835
        • Pfizer Investigational Site
      • Yokohama, Kanagawa, Japan, 2250012
        • Pfizer Investigational Site
    • Kumamoto
      • Yatsushiro, Kumamoto, Japan, 8660043
        • Pfizer Investigational Site
    • Nagano
      • Matsumoto, Nagano, Japan, 3908510
        • Pfizer Investigational Site
    • Osaka
      • Sakai, Osaka, Japan, 5900018
        • Pfizer Investigational Site
    • Saga
      • Kanzaka, Saga, Japan, 8420192
        • Pfizer Investigational Site
    • Saitama
      • Misato, Saitama, Japan, 3410018
        • Pfizer Investigational Site
    • Shiga
      • Kusatsu, Shiga, Japan, 5250037
        • Pfizer Investigational Site
    • Tokyo
      • Bunkyo, Tokyo, Japan, 1120012
        • Pfizer Investigational Site
      • Chiyoda, Tokyo, Japan, 1000006
        • Pfizer Investigational Site
      • Chiyoda, Tokyo, Japan, 1018643
        • Pfizer Investigational Site
      • Itabashi, Tokyo, Japan, 1730004
        • Pfizer Investigational Site
      • Katsushika, Tokyo, Japan, 1250041
        • Pfizer Investigational Site
      • Kodaira, Tokyo, Japan, 1858551
        • Pfizer Investigational Site
      • Minato, Tokyo, Japan, 1070052
        • Pfizer Investigational Site
      • Nakano, Tokyo, Japan, 1640012
        • Pfizer Investigational Site
      • Setagaya, Tokyo, Japan, 1540012
        • Pfizer Investigational Site
      • Setagaya-ku, Tokyo, Japan, 1540004
        • Pfizer Investigational Site
      • Shibuya, Tokyo, Japan, 1500001
        • Pfizer Investigational Site
      • Shibuya, Tokyo, Japan, 1510053
        • Pfizer Investigational Site
      • Shinagawa, Tokyo, Japan, 1410021
        • Pfizer Investigational Site
      • Shinagawa, Tokyo, Japan, 1410022
        • Pfizer Investigational Site
      • Shinagawa, Tokyo, Japan, 1420021
        • Pfizer Investigational Site
      • Shinjyuku, Tokyo, Japan, 1600023
        • Pfizer Investigational Site
      • Suginami, Tokyo, Japan, 1660003
        • Pfizer Investigational Site
      • Taito, Tokyo, Japan, 1100003
        • Pfizer Investigational Site
      • Toshima, Tokyo, Japan, 1700002
        • Pfizer Investigational Site
    • Toyko
      • Meguro, Toyko, Japan, 1520012
        • Pfizer Investigational Site
    • Yamaguchi
      • Ube, Yamaguchi, Japan, 7558505
        • Pfizer Investigational Site
  • United States
    • California
      • Arcadia, California, United States, 91007
        • Pfizer Investigational Site
      • Beverly Hills, California, United States, 90210
        • Pfizer Investigational Site
      • Cerritos, California, United States, 90703
        • Pfizer Investigational Site
      • Garden Grove, California, United States, 92845
        • Pfizer Investigational Site
      • Los Alamitos, California, United States, 90720
        • Pfizer Investigational Site
    • Florida
      • St. Petersburg, Florida, United States, 33702
        • Pfizer Investigational Site
    • Georgia
      • Atlanta, Georgia, United States, 30328
        • Pfizer Investigational Site
      • Smyrna, Georgia, United States, 30080
        • Pfizer Investigational Site
    • Illinois
      • Libertyville, Illinois, United States, 60048
        • Pfizer Investigational Site
    • Ohio
      • Dayton, Ohio, United States, 45408
        • Pfizer Investigational Site
    • Rhode Island
      • East Providence, Rhode Island, United States, 02914
        • Pfizer Investigational Site
    • South Carolina
      • Columbia, South Carolina, United States, 29201
        • Pfizer Investigational Site
    • Tennessee
      • Memphis, Tennessee, United States, 38117
        • Pfizer Investigational Site
    • Texas
      • Dallas, Texas, United States, 75230
        • Pfizer Investigational Site
      • San Antonio, Texas, United States, 78229
        • Pfizer Investigational Site
    • Utah
      • Salt Lake City, Utah, United States, 84107
        • Pfizer Investigational Site
    • Washington
      • Kirkland, Washington, United States, 98033
        • Pfizer Investigational Site
      • Seattle, Washington, United States, 98104
        • Pfizer Investigational Site
    • Wisconsin
      • Brown Deer, Wisconsin, United States, 53223
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult, outpatient with primary diagnosis of Major Depressive Disorder (depressive symptoms for at least 30 days prior to screening)
  • Hamilton Psychiatric Rating Scale for Depression (HAM-D 17) total score of >= 20
  • Clinical Global Impressions Scale-Severity (CGI-S) score of >= 4

Exclusion Criteria:

  • Clinical instability - 25% or greater increase/decrease in HAM-D 17 total score from screening to baseline
  • Significant risk of suicide as assessed by clinician judgement, HAM-D 17 and Columbia Suicide-Severity Rating Scale scores Other eligibility criteria also apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Drug: placebo
Matching placebo tablets (25 or 50 mg). Daily dosing for 10 +/- 4 days during a placebo lead-in period, and then 8 weeks during the double-blind period.
Experimental: Desvenlafaxine succinate sustained-release 50 mg
Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)
50 mg tablet, once daily dosing for 8 weeks
Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)
25 mg tablet, once daily dosing for 8 weeks
Experimental: Desvenlafaxine succinate sustained-release 25 mg
Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)
50 mg tablet, once daily dosing for 8 weeks
Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)
25 mg tablet, once daily dosing for 8 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in HAM-D17 Total Score at the Final On-therapy (FOT)Evaluation (Week 8 or ET)
Time Frame: Baseline and Week 8 (or ET)
HAM-D17: a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.
Baseline and Week 8 (or ET)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Categorical Scores on CGI-Improvement (CGI-I) at FOT Evaluation (Week 8 or ET)
Time Frame: Week 8 (or ET)
CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Week 8 (or ET)
Change From Baseline in Mean CGI-S Score at FOT Evaluation (Week 8 or ET)
Time Frame: Baseline and Week 8 (or ET)
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected.
Baseline and Week 8 (or ET)
Change From Baseline in MADRS Total Score at FOT Evaluation (Week 8 or ET)
Time Frame: Baseline and Week 8 (or ET)
MADRS measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Baseline and Week 8 (or ET)
Change From Baseline in HAM-D6 Total Score at FOT Evaluation (Week 8 or ET)
Time Frame: Baseline and Week 8 (or ET)
HAM-D6: a standardized, clinician-administered rating scale that assesses 6 items characteristically associated with major depression and is a subset of HAM-D17. HAM-D6 score ranges from 0-22. The scale uses HAM-D17 items: 1, 2, 7, 8, 10 and 13. Item 13 is scored 0-2 and all others are scored 0-4.
Baseline and Week 8 (or ET)
Number of Participants With a Response on the HAM-D17 at FOT Evaluation (Week 8 or ET)
Time Frame: Week 8 (or ET)
A HAM-D17 responder was defined as a participant with a 50% or greater decrease from baseline in HAM-D17 score. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.
Week 8 (or ET)
Number of Participants in Remission Based on the HAM-D17 at FOT Evaluation (Week 8 or ET)
Time Frame: Week 8 (or ET)
Remission was defined as a HAM-D17 score of less than or equal to 7. HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Individual items are scored on either a 3 point (0 to 2) or a 5 point scale (0 to 4), with 0=none/absent and 4=most severe, for a maximum total score of 50.
Week 8 (or ET)
Number of Participants With a Response on the MADRS Score at FOT Evaluation (Week 8 or ET)
Time Frame: Week 8 (or ET)
A MADRS responder was defined as a participant with a 50% or greater decrease from baseline in MADRS score. It measures the overall severity of depressive symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
Week 8 (or ET)
Number of Participants With a Response on the CGI-I Score at FOT Evaluation (Week 8 or ET)
Time Frame: Week 8 (or ET)
CGI-I responder was defined as a participant with a score of 1 (very much improved) or 2 (much improved) on the CGI-I. CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Week 8 (or ET)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Population Pharmacokinetics for Desvenlafaxine Plasma Concentrations
Time Frame: Week 2, 4 and 8 (or ET)
Relationship of demographic variables (age, gender, food, race, creatinine, aspartate aminotransaminase, alanine transaminase, bilirubin and concomitant medications) were examined by fitting measured DVS plasma concentrations to a 1 compartment model with first order absorption. Demographic variables were examined for clearance (CL/F), volume of distribution (V/F), Steady Area under Curve (AUC) using nonlinear mixed effects modeling. Final parameter estimates for demographic factors effecting CL/F, V/F and AUC were determined.
Week 2, 4 and 8 (or ET)
Change From Baseline in SDS at FOT Evaluation (Week 8 or ET)
Time Frame: Baseline and Week 8 (or ET)
SDS: a self-administered tool that measures functional impairment in 3 domains: Work/School, Social Life, and Family Life/Home Responsibilities. The participant rates the extent to which each of these domains is impaired by his/her symptoms using a 10 point visual analog scale: (0=not at all impaired, 10=extremely impaired) for a total maximum score of 30.
Baseline and Week 8 (or ET)
Change From Baseline in WHO-5 Total Score at FOT Evaluation (Week 8 or ET)
Time Frame: Baseline and Week 8 (or ET)
WHO-5 evaluates positive psychological well-being. WHO-5 consists of 5 questions and each is rated on a 6-point scale. The total score ranges from 0 to 25 (0= worst possible quality of life; 25=best possible quality of life).
Baseline and Week 8 (or ET)
Percentage of Participants With Sexual Dysfunction at FOT Evaluation (Week 8 or ET)
Time Frame: Week 8 (or ET)
ASEX scale includes 5 questions that evaluate sexual function exclusively during the week prior to completion in the following areas: libido, excitability and ability to reach orgasm. Sexual dysfunction=an ASEX total score of 19 or greater, or a score of 5 or greater on any item, or a score of 4 or greater on any 3 items. Participants who have had no sexual activity during the prior week should be instructed to not complete questions 3 through 5.
Week 8 (or ET)
Number of Participants With Categorical Scores on the C-SSRS at FOT Evaluation (Week 8 or ET)
Time Frame: Week 8 (or ET)
C-SSRS mapped into C-CASA(1-7) to assess whether participant:completed suicide(1),suicide attempt(2)(response of "Yes" on "Actual Attempt"),preparatory acts toward imminent suicidal behavior (3)("Yes" on "Preparatory Acts or Behavior"),suicidal ideation (4)("Yes" on "Wish to be dead","Non-Specific Active Suicidal Thoughts","Active Suicidal Ideation with methods without Intent to Act or Some Intent to Act,without Specific Plan or with Specific Plan and Intent),any suicidal behavior or ideation,self-injurious behaviour(7)("Yes" on "Has subject engaged in Non-suicidal Self-Injurious Behavior").
Week 8 (or ET)
Discontinuation-Emergent Signs and Symptoms (DESS) Total Score
Time Frame: Week 8 to 10 (or ET)
DESS: a clinician-administered 43-item assessment that evaluates discontinuation-emergent symptoms resulting from the withdrawal from test article. The DESS total score is the sum of the number of "new symptoms" and "old (but worse) symptoms" (1) and 0 for "old and unchanged symptom," "absent," or "old symptom but improved" for a total possible range of 0 to 43. A higher score indicates more symptoms.
Week 8 to 10 (or ET)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 25, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 25, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 26, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 10, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 3151A1-3359
  • B2061003
  • 3151A1-3359-WW

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Major Depressive Disorder

Clinical Trials on Desvenlafaxine Succinate Sustained-Release (DVS SR)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings