STEVIE: A Study of Vismodegib in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma

Basal Cell Carcinoma Clinical Trial

Official title:

A Single Arm, Open-label, Phase II, Multicentre Study, to Assess the Safety of Vismodegib (GDC-0449) in Patient With Locally Advanced or Metastatic Basal Cell Carcinoma (BCC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01367665
• Other study ID #: MO25616
• Secondary ID: 2011-000195-34
• Status: Completed
• Phase: Phase 2
• Start date: July 1, 2011
• Est. completion date: June 14, 2017

Study information

• Verified date: March 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This single-arm, open-label, multi-center study will evaluate the safety and efficacy of vismodegib (GDC-0449) in patients with locally advanced or metastatic basal cell carcinoma. Patients will receive oral doses of vismodegib 150 mg once daily until disease progression or unacceptable toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1232
• Est. completion date: June 14, 2017
• Est. primary completion date: June 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients, >/=18 years of age

• Metastatic or locally advanced basal cell carcinoma considered inoperable or that surgery is contraindicated and radiotherapy is contraindicated or inappropriate

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

Exclusion Criteria:

• Concurrent anti-tumor therapy

• Completion of the most recent anti-tumor therapy less than 21 days prior to the initiation of treatment

• Uncontrolled medical illness

Related Conditions & MeSH terms

• Basal Cell Carcinoma
• Carcinoma
• Carcinoma, Basal Cell

Intervention

Drug:
• vismodegib
150 mg once daily until disease progression or unacceptable toxicity

Locations

Country	Name	City	State
Argentina	Inst. de Oncologia Angel H. Roffo ; Servicio de Oncologia	Buenos Aires
Australia	CMAX A division of IDT Australia Limited	Adelaide	South Australia
Australia	Skin & Cancer Foundation	Carlton	Victoria
Australia	Premier Specialists	Kogarah	New South Wales
Australia	Skin and Cancer Foundation Australia	Westmead	New South Wales
Austria	LKH Graz; Abteilung für allgemeine Dermatologie	Graz
Austria	LKH Salzburg; Universitätsklinik für Dermatologie	Salzburg
Austria	Landesklinikum St. Pölten	St. Pölten
Austria	Medizinische Universität Wien; Univ.Klinik für Dermatologie	Wien
Belgium	UZ Leuven Gasthuisberg	Leuven
Bosnia and Herzegovina	University Clinical Center of the Republic of Srpska	Banja Luka
Bosnia and Herzegovina	Clinic of Oncology, University Clinical Center Sarajevo	Sarajevo
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Bulgaria	District Oncology Dispensary; Department for Oncology and Dermatology	Plovdiv
Bulgaria	National Specialized Hospital for Active Oncology Treatment; Dermatology Clinic	Sofia
Canada	Western Canada Dermatology Institute	Edmonton	Alberta
Canada	London Regional Cancer Centre	London	Ontario
Canada	Victoria Park MediSpa	Montreal	Quebec
Canada	Centre de Recherche Dermatologique du Quebec Metropolitain (CRDQ)	Quebec
Canada	Dr. Nowell Solish Cosmetic Dermatology	Toronto	Ontario
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
Colombia	Inst. Nacional de Cancerologia; Clinica de Seno	Bogota
Colombia	Riesgo De Fractura; Rheumatology	Bogota
Colombia	Hemato Oncologos S.A.	Cali
Colombia	Reumalab Sas; Rheumatology	Medellin
Colombia	Hospital Pablo Tobon Uribe	Medellin-Antioquia
Croatia	Clinical Hospital Sisters of Mercy	Zagreb
Czechia	Nemocnice Ceske Budejovice	Ceske Budejovice
Czechia	Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology	Hradec Kralove
Czechia	Fakultní nemocnice Ostrava; Kožní oddelení	Ostrava
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha
Czechia	Fakultni Thomayerova Nemocnice; Onkologicke Oddeleni	Praha
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Czechia	Fakultni nemocnice v Motole	Praha 5
Denmark	Herlev Hospital; Onkologisk afdeling	Herlev
Finland	Helsinki University Central Hospital; Skin & Allergy Hospital	Helsinki
Finland	Kuopion yliopistollinen sairaala	Kuopio
France	Hopital Saint Andre CHU De Bordeaux; Dermatologie	Bordeaux
France	Hopital Ambroise Pare; Sce Dermatologie	Boulogne-billancourt
France	Chu Site Du Bocage;Dermatologie	Dijon
France	Hopital Claude Huriez; Sce Dermatologie	Lille
France	Hopital Timone Adultes; Dermatologie	Marseille
France	Hopital Saint Eloi; CHU de Montpellier; Svc de Dermatologie	Montpellier
France	Hopital Hotel Dieu Et Hme; Clinique Dermatologique	Nantes
France	Hopital Saint Louis; Dermatologie 1	Paris
France	Centre Hospitalier Lyon Sud; Dermatologie	Pierre Benite
France	Hôpital Larrey Université Paul Sabatier; Service Dermatologie	Toulouse
France	Institut Gustave Roussy; Comite 5	Villejuif
Germany	Charité Campus Mitte; Hauttumorcentrum Charité (HTCC); Klinik für Dermatologie, Venerologie und Alle	Berlin
Germany	Vivantes Klinikum Spandau	Berlin
Germany	Elbekliniken Buxtehude; Klinik für Dermatologie	Buxtehude
Germany	Klinikum Dortmund gGmbH Klinikzentrum Mitte	Dortmund
Germany	Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Dermatologie	Dresden
Germany	Universitätsklinikum Düsseldorf; Hautklinik	Düsseldorf
Germany	HELIOS Klinikum Erfurt; Klinik für Dermatologie & Allergologie	Erfurt
Germany	Universitätsklinikum Essen	Essen
Germany	Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie	Frankfurt
Germany	Universitätsklinikum Freiburg Universitäts-Hautklinik	Freiburg
Germany	Universitätsmedizin Greifswald; Klinik für MKG-Chirurgie und Plastische Operationen	Greifswald
Germany	Universitätsklinikum Hamburg-Eppendorf Zentrum f.Innere Medizin Klinik f.Dermatologie	Hamburg
Germany	Medizinische Hochschule Hannover; Klinik für Dermatologie, Allergologie und Venerologie	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Klinikum am Gesundbrunnen; Tumorzentrum	Heilbronn
Germany	Klinikum Kassel; Hautklinik	Kassel
Germany	UNI-Klinikum Campus Kiel Klinik f.Dermatologie Tagesklinik f.Dermatologie	Kiel
Germany	Klinik der Uni zu Köln; Klinik & Poliklinik fuer Dermatologie & Venerologie	Köln
Germany	Uni Schleswig-Holstein; Klinik für Dermatologie, Allergologie und Venerologie (Hautklinik)	Lübeck
Germany	Klinikum d.Stadt Ludwigshafen Hautklinik	Ludwigshafen
Germany	Universitätsklinikum Magdeburg; Hautklinik; Klinik für Dermatologie und Venerologie	Magdeburg
Germany	Klinikum Mannheim Klinik fuer Dermatologie, Venerologie und Allergologie	Mannheim
Germany	Universitätsklinikum Marburg Klinik f. Dermatologie	Marburg
Germany	Universitätsklinikum Münster; Klinik für Hautkrankheiten; Allgemeine Dermatologie und Venerologie	Muenster
Germany	Klinikum der LMU München; Klinik und Poliklinik für Dermatologie und Allergologie	München
Germany	Klinikum rechts der Isar der TU München; Klinik & Poliklinik für Dermatologie und Allergologie	München
Germany	Klinikum Nürnberg Nord; Hautklinik; Klinik für Dermatologie	Nürnberg
Germany	Harzklinikum Dorothea Christiane Erxleben GmbH; Klinik für Dermatologie und Allergologie	Quedlinburg
Germany	Universitätsklinikum Regensburg; Klinik und Poliklinik für Dermatologie	Regensburg
Germany	Universitaets-Hautklinik Tuebingen	Tübingen
Germany	Universitätsklinikum Würzburg; Klinik und Poliklinik für Dermatologie Venerologie u. Allergologie	Würzburg
Greece	Andreas Syggros Hospital; 1st University Dermatology Clinic; Oncology Department	Athens
Greece	Laiko General Hospital; 1St Pathological Clinic	Athens
Greece	Univ General Hosp Heraklion; Medical Oncology	Heraklion
Greece	University General Hospital of loannina; Dermatology and Venereal Diseases Clinic	Ioannina
Greece	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki
Hungary	Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly	Budapest
Hungary	Semmelweis Egyetem; Bor-, Nemikortani es Boronkologiai Klinika	Budapest
Hungary	Debreceni Egyetem Klinikai Központ; Borgyógyászati Klinika	Debrecen
Hungary	Kaposi Mor Teaching Hospital	Kaposvár
Hungary	Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin.Kozp.	Szeged
Ireland	Cork University Hospital; Dermatology Dept	Cork
Ireland	St Vincent'S Uni Hospital; Medical Oncology	Dublin
Israel	Rambam Medical Center	Halfa
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Rabin Medical Center-Beilinson Campus	Petach Tikva
Israel	Sheba Medical Center; Tel Hashomer	Ramat Gan
Italy	A.O.U. Ospedali Riuniti Umberto I-G.M.Lancisi-G.Salesi Ancona;S.O.D. MED.Interna-Clinica Oncologica	Ancona	Marche
Italy	Policlinico Sant'Orsola Malpighi; U.O. Dermatologia	Bologna	Emilia-Romagna
Italy	Università di Brescia; Dipartimento di Dermatologia	Brescia	Lombardia
Italy	Ospedale Antonio Perrino; Oncologia Medica	Brindisi	Puglia
Italy	Ospedale Armando Businco; Dermatologia	Cagliari	Sardegna
Italy	Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico	Candiolo	Piemonte
Italy	Ospedale IOT- Palagi Dermatologia 2	Firenze	Toscana
Italy	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria
Italy	Ospedale San Salvatore (ASL-01); Dip. di Dermatologia U.O.S. di Dermatologia Oncol	L'Aquila	Abruzzo
Italy	I.R.S.T. Srl - Meldola - FC; Day Hospital Oncologico	Meldola	Emilia-Romagna
Italy	Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia	Milano	Lombardia
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori;S.S. Trattamento MedicoTumori dellaTesta e delCollo	Milano	Lombardia
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica	Milano	Lombardia
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda	Padova	Veneto
Italy	Azienda Ospedaliera Umberto I; Clinica Dermatologica	Roma	Lazio
Italy	Fondazione Ptv Policlinico Tor Vergata; Dermatologia	Roma	Lazio
Italy	Istituto Dermatologico San Gallicano IRCCS; Dermatologia Oncolgica	Roma	Lazio
Italy	Istituto Dermopatico dell'Immacolata (IDI)-IRCCS; IV Divisione Oncologica e Dermatologia Oncologica	Roma	Lazio
Italy	IRCCS Istituto Clinico Humanitas; Farmacia	Rozzano	Lombardia
Italy	A.O.U. Senese Policlinico Santa Maria Alle Scotte	Siena	Toscana
Lithuania	National Cancer Institute	Vilnius
Mexico	Hospital General de México	Mexico City	Mexico CITY (federal District)
Netherlands	Academ Ziekenhuis Groningen; Medical Oncology	Groningen
Netherlands	LUMC; Dermatologie	Leiden
Netherlands	Maastricht University Medical Centre; Dermatologie	Maastricht
Netherlands	Erasmus MC; Dermatology	Rotterdam
New Zealand	Waitemata District Health; General Surgery	Takapuna
Norway	Oslo Universitetssykehus HF; Radiumhospitalet	Oslo
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii	Gdansk
Poland	DERMED Centrum Medyczne; Sp zoo	Lodz
Poland	Centrum Diagnostyki Znamion	Poznan
Poland	Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie; Klinika Onkologiczna	Warsaw
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Romania	Institutul Oncologic Prof. Dr. Al. Trestioreanu Bucuresti	Bucuresti
Romania	Prof. Dr. I. Chiricuta Institute of Oncology	Cluj Napoca
Romania	Oncology Center Sf. Nectarie	Craiova
Romania	Spital Clinic Judetean Mures; Oncologie	Targu Mures
Romania	S.C. Life Search S.R.L; Medical Oncology Clinic	Timisoara
Russian Federation	FSBI "National Medical Research Center of Oncology N.N. Blokhin"	Moscow
Russian Federation	Moscow city oncology hospital #62 of Moscow Healthcare Department	Moscow
Russian Federation	FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF	St Petersburg	Leningrad
Russian Federation	Saint-Petersburg City Clinical Oncology Dispensary	St Petersburg
Serbia	Institute for Oncology and Radiology of Serbia; Medical Oncology	Belgrade
Serbia	Military Medical Academy	Belgrade
Slovakia	Fakultna Nemocnica Roosevelta	Banska Bystrica
Slovenia	Institute of Oncology Ljubljana	Ljubljana
Spain	Fundacion Hospital de Alcorcon; Servicio de Dermatologia	Alcorcon	Madrid
Spain	Hospital Universitario del Sureste; Servicio de Dermatologia	Arganda del Rey	Madrid
Spain	Hospital Clinic i Provincial; Servicio de dermatología	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Dermatologia	Barcelona
Spain	Hospital de Cruces; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Hospital Reina Sofia; Servicio de dermatología	Cordoba
Spain	Hospital Universitario Virgen de las Nieves; Servicio de Oncologia	Granada
Spain	Hospital General Universitario de Guadalajara; Servicio de Dermatologia	Guadalajara
Spain	Hospital de Gran Canaria Dr. Negrin; Servicio de Dermatologia	Las Palmas de Gran Canaria	LAS Palmas
Spain	Complejo Asistencial Universitario de Leon; Servicio de Oncologia	Leon
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario J.M Morales Meseguer; Servicio de Dermatologia	Murcia
Spain	Hospital Univ. Central de Asturias; Servicio de Dermatologia	Oviedo	Asturias
Spain	Hospital Universitario Son Espases; Servicio de Oncologia	Palma De Mallorca	Islas Baleares
Spain	Clinica Universitaria de Navarra; Servicio de Dermatologia	Pamplona	Navarra
Spain	Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Dermatologia	Santa Cruz de Tenerife	Tenerife
Spain	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla
Spain	Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Dermatologia	Toledo
Spain	Hospital General Universitario de Valencia; Servicio de oncologia	Valencia
Spain	Instituto Valenciano Oncologia; Oncologia Medica	Valencia
Spain	Hospital Universitario Miguel Servet; Servicio Dermatologia	Zaragoza
Sweden	Skånes Onkologiska Klinik, Universitetssjukhuset	Lund
Sweden	Karolinska Universitetssjukhuset, Solna	Stockholm
Switzerland	Universitätsspital Zürich; Dermatologische Klinik	Zürich
Turkey	Ankara Numune Training and Research Hospital; Dermatology	Ankara
Turkey	Gazi Universitesi Tip Facultesi; Dept. of Dermatology	Ankara
Turkey	Istanbul Uni of Medicine Faculty; Oncology Dept	Istanbul
Turkey	Dokuz Eylul University Medicine Faculty; Dermatology	Izmir
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye, Ankara
United Kingdom	Addenbrookes Hospital; Cambridge Cancer Trials Centre, S4 Box 279	Cambridge
United Kingdom	Western Infirmary; Division of Cardiovascular and Medical Sciences	Glasgow
United Kingdom	Royal Marsden Hospital - London	London
United Kingdom	St Thomas Hospital	London
United Kingdom	Freeman Hospital; Northern Centre For Cancer Care	New Castle Upon Tyne
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United Kingdom	The Royal Marsden Hospital	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Bosnia and Herzegovina,  Brazil,  Bulgaria,  Canada,  Colombia,  Croatia,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Lithuania,  Mexico,  Netherlands,  New Zealand,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  Slovenia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Experienced Any Adverse Events (AEs), AEs Grade 3 or 4, AEs Leading to Drug Interruptions or Discontinuations and Any Serious Adverse Events (SAEs)	Adverse events were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living with inability to perform bathing, dressing and undressing, feeding self, using the toilet, taking medications but not bedridden. Grade 4: An immediate threat to life. Urgent medical intervention is required in order to maintain survival.	Baseline to the data cut-off of 14 June 2017 (up to 6 years)
Primary	Percentage of Participants Who Died Due to Adverse Events, Disease Progression or Other Reasons	Reasons for "other" included "unknown," "natural causes," "cardiac decompensation," "general state alteration," "deterioration of general state," "clinical deterioration taking into consideration patient's age," "old age," and "disease progression of mediastinal squamous cell carcinoma (SCC)."	Baseline to the data cut-off of 14 June 2017 (up to 6 years)
Primary	Percentage of Participants Who Report a Shift in NCI CTCAE Grades to 3/4 in Hematology and Biochemistry Laboratory Parameters		Baseline to the data cut-off of 14 June 2017 (up to 6 years)
Primary	Exposure to Study Treatment: Duration on Treatment	Duration on treatment was the number of days between first and last dose of study treatment.	Baseline to the data cut-off of 14 June 2017 (up to 6 years)
Primary	Exposure to Study Treatment - Dose Intensity	Dose intensity was defined as the percentage of actual number of doses received versus planned.	Baseline to the data cut-off of 14 June 2017 (up to 6 years)
Secondary	Best Overall Response Rate (BORR)	BORR was defined as the percentage of participants achieving either a complete response (CR) or a partial response (PR) as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) required a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Baseline to the data cut-off of 14 June 2017 (up to 6 years)
Secondary	Duration of Response	Duration of response was defined as the time interval between the date of the earliest qualifying response (CR or PR) and the date of disease progression or death for any cause. Median duration of response was estimated using Kaplan-Meier estimates.	Baseline to the data cut-off of 14 June 2017 (up to 6 years)
Secondary	Time to Response	Time to response was defined as the interval between the date of first treatment and the date of first documentation of confirmed CR or PR (whichever occur first).	Baseline to the data cut-off of 14 June 2017 (up to 6 years)
Secondary	Progression-Free Survival (PFS)	PFS was defined as the time interval between the date of the first therapy and the date of progression or death for any causes, whichever occurs first. Disease progression was assessed by the investigator.	Baseline to the data cut-off of 14 June 2017 (up to 6 years)
Secondary	Overall Survival (OS)	OS was defined as the time from the date of first treatment to the date of death, regardless of the cause of death.	Baseline to the data cut-off of 14 June 2017 (up to 6 years)
Secondary	Change From Baseline Scores of Skindex-16 Questionnaire Domains of Emotion, Function and Symptom	The Skindex-16 questionnaire includes three domains for the assessment of the effects of skin disease on participants' quality of life: symptoms, emotions and function. For each domain, responses from the questionnaire were transformed to a linear scale of 100 varying from 0 (never bothered, i.e., best) to 100 (always bothers, i.e., worst).	Baseline to the data cut-off date of 14 June 2017 (up to 6 years).
Secondary	Percentage of Participants With a = 30% Reduction in Disease-Related Symptoms According to MDASI Scale	M.D. Anderson Symptom Inventory (MDASI) scale. The MDASI core instrument is a 19-item patient self-report questionnaire whose items comprise two scales, symptom severity and symptom interference. For 13 items (i.e., pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, difficulty remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness or tingling), participants were asked to rate how severe the symptoms were when "at their worst" in the last 24 hours. For the remaining 6 items, participants were asked to rate how much the symptoms have interfered with 6 areas of functioning (i.e., general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours.	08-May-2013 (Protocol Version = 4) to the data cut-off date of 14 June 2017 (approximately 4 years and 1 month).
Secondary	Percentage of Participants With a = 30% Reduction in Composite Symptom Severity Score According to MDASI Scale	M.D. Anderson Symptom Inventory (MDASI) scale. The MDASI core instrument is a 19-item patient self-report questionnaire whose items comprise two scales, symptom severity and symptom interference. For 13 items (i.e., pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, difficulty remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness or tingling), participants were asked to rate how severe the symptoms were when "at their worst" in the last 24 hours. For the remaining 6 items, participants were asked to rate how much the symptoms have interfered with 6 areas of functioning (i.e., general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours.	08-May-2013 (Protocol Version = 4) to the data cut-off date of 14 June 2017 (approximately 4 years and 1 month).