A Study to Investigate the Efficacy and Safety of GSK1605786A in the Treatment of Subjects With Moderately-to-Severely Active Crohn's Disease

Crohn's Disease Clinical Trial

— SHIELD-1  

Official title:

A Randomised, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of GSK1605786A in the Treatment of Subjects With Moderately-to-Severely Active Crohn's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01277666
• Other study ID #: 114151
• Status: Completed
• Phase: Phase 3
• First received: January 13, 2011
• Last updated: August 21, 2017
• Start date: December 20, 2010
• Est. completion date: July 11, 2013

Study information

• Verified date: July 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of two doses (500 mg once daily and 500 mg twice daily) of GSK1605786A as compared to placebo over 12 weeks in adult subjects with moderately-to-severely active Crohn's disease. Efficacy will be assessed by proportion of subjects achieving response, defined as a decrease in Crohn's Disease Activity Index (CDAI) score of at least 100 points (clinical response). Clinical remission (CDAI score less than 150 points) will be evaluated as a key secondary endpoint. Safety will be assessed by recording of adverse events, clinical laboratory parameters, vital signs and electrocardiogram (ECG). Population pharmacokinetics will evaluate the two doses of GSK1605786A. Health outcomes assessments will include changes in Inflammatory Bowel Disease Questionnaire (IBDQ), Short Form-36 version 2 (SF-36v2), EQ-5D and Work Productivity and Activity Impairment-CD (WPAI-CD) and receipt of disability.

Description:

This is a multi-centre, randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy of two oral doses of GSK1605786A (500 mg once daily, 500 mg twice daily) as compared to placebo in the induction of clinical response over a 12-week treatment period in subjects with moderately-to-severely active Crohn's disease. Secondary objectives will include assessment of the safety and evaluation of the efficacy in induction of remission.

The study is planned to randomise approximately 600 subjects (200 subjects/group) with active Crohn's disease, diagnosed for at least 4 months with a documented history of disease in the small and/or large intestine, and characterised by a Crohn's Disease Activity Index (CDAI) score between 220 to and 450, inclusive. Subjects must have reported an inadequate response or intolerance to Crohn's disease treatment with corticosteroids or immunosuppressants. Inclusion of subjects who received prior treatment with a biologic anti-tumour necrosis factor (TNF) agent will be limited to approximately 50% of the study population. All subjects are required to have a diagnosis with identification of anatomic location of Crohn's disease, which has been established by visualisation of the gastrointestinal tract within 12 months of screening. Subjects who have not had a visualisation of the gastrointestinal tract within 12 months are required to undergo an endoscopic assessment during the screening period. Subjects will be required to have evidence of current active inflammation at the time of randomisation either by endoscopy or by inflammatory biomarkers [elevated C-reactive protein (CRP) greater than the upper limit of normal (ULN) plus a positive faecal calprotectin test]. Subjects who do not meet the requirements based on inflammatory biomarker test results will be required to qualify based on endoscopic assessment during screening. Subjects will be allowed to participate in the study while continuing on stable doses of agents typically used to treat Crohn's disease. Following the screening period, subjects will be randomised at baseline to receive blinded treatment with one of two doses of GSK1605786A (500 mg once daily or twice daily) or placebo for 12 weeks. Response and remission endpoints, using the CDAI, will be evaluated at Weeks 4, 8 and 12.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 608
• Est. completion date: July 11, 2013
• Est. primary completion date: July 11, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female subjects aged 18 years or older

• Written informed consent

• Diagnosis of Crohn's disease for greater than 4 months duration with small bowel and/or colonic involvement

• Confirmation of Crohn's disease established by visualisation of the gastrointestinal tract within the 12 months prior to screening or by screening endoscopy at study entry

• History of inadequate response and/or intolerance/adverse event leading to discontinuation of either corticosteroids or immunosuppressants

• Moderately-to-severely active disease characterised by a CDAI score between 220 and 450, inclusive, at Baseline

• Confirmation of current active Crohn's disease by screening endoscopy or inflammatory biomarkers [elevated C-reactive protein (greater than upper limit of normal) plus positive test for faecal calprotectin] at Screening

• Stable doses of permitted concomitant medications or having previously received, but are not currently receiving, medications for Crohn's disease

• Demonstrated ability to comply with Crohn's disease symptom recording using the interactive voice response system

• Females of child-bearing potential must be sexually inactive or commit to consistent and correct use of a contraceptive method of birth control with a failure rate of less than 1% for the duration of this study

Exclusion Criteria:

• If female: pregnant, has a positive pregnancy test or is breast-feeding

• Diagnosis of coeliac disease, follow a gluten-free diet to manage symptoms, or positive test for coeliac disease

• Diagnosis of ulcerative or indeterminate colitis

• Enterocutaneous, abdominal or pelvic fistulae with abscesses or fistulae likely to require surgery during the study period

• Bowel surgery, other than appendectomy, within 12 weeks prior to screen and/or has surgery planned or deemed likely for Crohn's disease during the study period

• Extensive colonic resection, subtotal or total colectomy

• Presence of ileostomies, colostomies or rectal pouches

• Known fixed symptomatic stenoses

• History of more than 3 small bowel resections or diagnosis of short bowel syndrome

• Chronic use of narcotics for chronic pain defined as daily use of one or more doses of narcotic containing medication

• Use of prohibited medications, including enteral feeding or elemental diet, within their specified time frames

1. Biologic use: Use of any biologic (tumour necrosis factor inhibitor or natalizumab) within 8 weeks prior to screening

2. Corticosteroid use: Use of parenteral glucocorticoids within 4 weeks prior to screening

3. Immunospressant use: Use of cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil within 4 weeks prior to screening

4. Intravenous antibiotic use: Use of intravenous antibiotics for Crohn's disease within 4 weeks prior to screening

5. Use of rectal treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to screening

6. Use of tube or enteral feeding, elemental diet, or parenteral alimentation within 2 weeks prior to screening

7. Leukocytapheresis or granulocytapheresis within 2 weeks prior to screening

• Positive immunoassay for Clostridium difficile

• Known human immunodeficiency virus (HIV) infection

• Known varicella, herpes zoster, or other severe viral infection within 6 weeks of screening

• Immunisation with a live vaccine within 4 weeks of screening, with the exception of influenza vaccine

• Active or latent tuberculosis infection

• Current sepsis or infections requiring intravenous antibiotic therapy for more than 2 weeks

• Evidence of hepatic dysfunction, viral hepatitis, or current or chronic history of liver disease including non-alcoholic steatohepatitis (NASH)

• Positive test for Hepatitis B or Hepatitis C antibody at screening

• Corrected QT interval of ECG (electrocardiogram) greater than or equal to 450 milliseconds

• Concurrent illness or disability that may affect the interpretation of clinical data, or otherwise contraindicates participation in this clinical study

• History or evidence of adenomatous colonic polyps that have not been removed

• History of evidence of colonic mucosal dysplasia

• Current evidence of, or has been treated for a malignancy within the past five years (other than localised basal cell, squamous cell skin cancer, cervical dysplasia, or any cancer in situ that has been resected)

• Any previous participation in a clinical study of GSK1605786A (formerly ChemoCentryx compound CCX282-B)

• Medical history of sensitivity to any of the components of GSK1605786A

• Use of any investigational product within 30 days prior to screening

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• GSK1605786A
500 mg twice daily, administered orally for 12 weeks
• GSK1605786A
500 mg once daily, administered orally for 12 weeks
• Placebo
Placebo capsules, administered orally for 12 weeks

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Adelaide	South Australia
Australia	GSK Investigational Site	Bankstown	New South Wales
Australia	GSK Investigational Site	Fitzroy	Victoria
Australia	GSK Investigational Site	Fremantle	Western Australia
Australia	GSK Investigational Site	Hersten	Queensland
Australia	GSK Investigational Site	Kurralta Park	South Australia
Australia	GSK Investigational Site	Prahran	Victoria
Austria	GSK Investigational Site	Hall in Tirol
Austria	GSK Investigational Site	Linz
Austria	GSK Investigational Site	Wien
Austria	GSK Investigational Site	Wien
Belgium	GSK Investigational Site	Bonheiden
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Edegem
Belgium	GSK Investigational Site	Gent
Belgium	GSK Investigational Site	Kortrijk
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Roeselare
Canada	GSK Investigational Site	Abbotsford	British Columbia
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	Hamilton	Ontario
Canada	GSK Investigational Site	Hamilton	Ontario
Canada	GSK Investigational Site	Kingston	Ontario
Canada	GSK Investigational Site	Levis	Quebec
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Richmond Hill	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
Canada	GSK Investigational Site	Victoria	British Columbia
Canada	GSK Investigational Site	Winnipeg	Manitoba
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Hradec Králové
Czechia	GSK Investigational Site	Olomouc
Czechia	GSK Investigational Site	Ostrava - Vitkovice
Czechia	GSK Investigational Site	Praha 10
Czechia	GSK Investigational Site	Praha 4
Czechia	GSK Investigational Site	Praha 7
Czechia	GSK Investigational Site	Praha 9
Denmark	GSK Investigational Site	Aalborg
Denmark	GSK Investigational Site	Aarhus
Denmark	GSK Investigational Site	Herlev
Denmark	GSK Investigational Site	Hvidovre
Denmark	GSK Investigational Site	Odense
France	GSK Investigational Site	Amiens cedex 1
France	GSK Investigational Site	Clichy cedex
France	GSK Investigational Site	Lille cedex
France	GSK Investigational Site	Nantes cedex 1
France	GSK Investigational Site	Nice cedex 3
France	GSK Investigational Site	Paris cedex 10
France	GSK Investigational Site	Pessac cedex
France	GSK Investigational Site	Saint-Priest en Jarez
France	GSK Investigational Site	Vandoeuvre Les Nancy
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Braunschweig	Niedersachsen
Germany	GSK Investigational Site	Brinkum/Stuhr	Niedersachsen
Germany	GSK Investigational Site	Dessau	Sachsen-Anhalt
Germany	GSK Investigational Site	Frankfurt am Main	Hessen
Germany	GSK Investigational Site	Freiburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Halle	Sachsen-Anhalt
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Jena	Thueringen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Ludwigshafen	Rheinland-Pfalz
Germany	GSK Investigational Site	Minden	Nordrhein-Westfalen
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Hungary	GSK Investigational Site	Bekescsaba
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Szekszárd
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Holon
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Kfar Saba
Israel	GSK Investigational Site	Petach Tikva
Israel	GSK Investigational Site	Tel Aviv
Italy	GSK Investigational Site	Genova
Italy	GSK Investigational Site	Modena
Italy	GSK Investigational Site	Palermo	Sicilia
Italy	GSK Investigational Site	Roma
Italy	GSK Investigational Site	Roma
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Pusan
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Wonju
Netherlands	GSK Investigational Site	Almere
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	EDE
Netherlands	GSK Investigational Site	Heerlen
Netherlands	GSK Investigational Site	Rotterdam
New Zealand	GSK Investigational Site	Auckland
New Zealand	GSK Investigational Site	Dunedin
New Zealand	GSK Investigational Site	Hamilton
New Zealand	GSK Investigational Site	Lower Hutt
New Zealand	GSK Investigational Site	Otahuhu
New Zealand	GSK Investigational Site	Tauranga.
Norway	GSK Investigational Site	Ålesund
Norway	GSK Investigational Site	Bodø
Norway	GSK Investigational Site	Oslo
Norway	GSK Investigational Site	Tønsberg
Norway	GSK Investigational Site	Tromsø
Norway	GSK Investigational Site	Trondheim
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Elblag
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Sopot
Poland	GSK Investigational Site	Torun
Poland	GSK Investigational Site	Wroclaw
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Nitra
Slovakia	GSK Investigational Site	Nove Mesto nad Vahom
Slovakia	GSK Investigational Site	Presov
Slovakia	GSK Investigational Site	Trnava
South Africa	GSK Investigational Site	Bellville
South Africa	GSK Investigational Site	Claremont
South Africa	GSK Investigational Site	Observatory
South Africa	GSK Investigational Site	Parktown
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Elche
Spain	GSK Investigational Site	Galdakao/Vizcaya
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Sabadell (Barcelona)
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Lund
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Umeå
United Kingdom	GSK Investigational Site	Birmingham
United Kingdom	GSK Investigational Site	Bristol
United Kingdom	GSK Investigational Site	Edinburgh
United Kingdom	GSK Investigational Site	Harrow	Middlesex
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Newcastle-upon-Tyne
United Kingdom	GSK Investigational Site	Nottingham
United Kingdom	GSK Investigational Site	Oxford
United Kingdom	GSK Investigational Site	Salford
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Ann Arbor	Michigan
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Chapel Hill	North Carolina
United States	GSK Investigational Site	Chesterfield	Michigan
United States	GSK Investigational Site	Chevy Chase	Maryland
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Egg Harbor City	New Jersey
United States	GSK Investigational Site	Germantown	Tennessee
United States	GSK Investigational Site	Great Neck	New York
United States	GSK Investigational Site	Hamden	Connecticut
United States	GSK Investigational Site	Hammond	Louisiana
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Jackson	Mississippi
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Lakewood	Colorado
United States	GSK Investigational Site	Lebanon	New Hampshire
United States	GSK Investigational Site	Lee's Summit	Missouri
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Little Rock	Arizona
United States	GSK Investigational Site	Littleton	Colorado
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Maitland	Florida
United States	GSK Investigational Site	Monroe	Louisiana
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	Oak Lawn	Illinois
United States	GSK Investigational Site	Pasadena	Texas
United States	GSK Investigational Site	Port Orange	Florida
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Rochester	Minnesota
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Towson	Maryland
United States	GSK Investigational Site	Troy	Michigan
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	Tupelo	Mississippi
United States	GSK Investigational Site	Voorhees	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Norway,  Poland,  Slovakia,  South Africa,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 12	CDAI is a number which consists of information collected from a 7-day diary from the participants regarding symptoms. Remission is considered a score of 150 or less. Active disease is considered 200 or greater. A response to therapy is considered a decline in CDAI score of 70-points from baseline. The score was algorithmically derived from the sum of participant reported Crohn's disease symptoms recorded over 7 days and investigator recorded assessments of the participant's condition, laboratory parameters and use of anti-diarrhoeal medication. CDAI score was calculated based on the data collected in the diary card. The total CDAI score ranged from 0 to approximately 600, where higher scores indicate more severe disease. Both participants and investigators made their entries via IVRS each evening before going to bed. Percentage of participants with CDAI response at Week 12 was presented.	Week 12
Secondary	Percentage of Participants With CDAI Remission at Week 12	CDAI is a recognized scoring system to categorize disease severity with scores of >= 220 to <= 450 describing the moderately-to-severely active population. Clinical remission is defined as a CDAI score < 150 points if baseline CDAI is >= 150. If baseline CDAI is <150, the participant was not considered in remission. Participants with missing CDAI scores were considered not in remission according to the missing=no effect imputation. Percentage of participants in clinical remission at Week 12 was presented.	Week 12
Secondary	Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >= 100 Points) at Both Week 8 and Week 12	Responders were defined as participants with CDAI decrease from baseline of >= 100 points. CDAI is a recognized scoring system to categorize disease severity with scores of >= 220 to <= 450 describing the moderately-to-severely active population. The score was algorithmically derived from the sum of participant reported Crohn's disease symptoms recorded over 7 days and investigator recorded assessments of the participant's condition, laboratory parameters and use of anti-diarrhoeal medication. Both participants and investigators made their entries via IVRS each evening before going to bed. Percentage of participants with CDAI decrease from baseline of >=100 points was presented.	At Week 8 and 12
Secondary	Percentage of Participants Achieving Clinical Remission (CDAI <150 Points) at Both Week 8 and Week 12	Clinical remission is defined as a CDAI score < 150 points if baseline CDAI is >= 150. If baseline CDAI is <150, the participant was not considered in remission. participants with missing CDAI scores were considered not in remission according to the missing=no effect imputation. Percentage of participants in clinical remission defined as a CDAI score of less than 150 points at other time points was presented.	Week 8 and 12
Secondary	Percentage of Participants With a Clinical Response (CDAI Decrease From Baseline of >=100 Points) at Week 8	CDAI is a recognized scoring system to categorize disease severity with scores of >= 220 to <= 450 describing the moderately-to-severely active population. The score was algorithmically derived from the sum of participant reported Crohn's disease symptoms recorded over 7 days and investigator recorded assessments of the participant's condition, laboratory parameters and use of anti-diarrhoeal medication. Both participants and investigators made their entries via IVRS each evening before going to bed. Percentage of Participants with a clinical response CDAI decrease from baseline of >=100 points at Week 8 was presented.	Week 8
Secondary	Percentage of Participant Achieving Clinical Remission (CDAI <150 Points) at Week 8	Clinical remission is defined as a CDAI score < 150 points if baseline CDAI is >= 150. If baseline CDAI is <150, the participant was not considered in remission. participants with missing CDAI scores were considered not in remission according to the missing=no effect imputation. Percentage of participants achieving clinical remission with CDAI <150 points at Week 8 was presented.	Week 8
Secondary	Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Both Weeks 8 and 12	The IBDQ is a 32-item IBD-specific health related quality of life instrument evaluating general activities of daily living, intestinal function, social performance, personal interactions, and emotional status. Each item response was graded from 1 to 7 for each area evaluated. A higher score indicated better function in that area. Total IBDQ score was obtained by summing up scores for all 32 questions. Total IBDQ score ranged from 32 to 224. A higher score indicated better quality of life and lower score indicated worse quality of life. Day 1 assessment was considered as Baseline. Change from Baseline was calculated by subtracting value at Baseline from value at Weeks 8 and 12.	Baseline (Week 0), Week 8 and Week 12
Secondary	Incidence of Adverse Events (AE) and Serious Adverse Events (SAE)	Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.	Up to Week 12