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ISRCTN41927312 | SNCTP000002483

Studio per valutare l’adesività di Flectoparin® Tissugel dopo applicazione del cerotto in soggetti sani

Datenbasis: BASEC (Import vom 20.04.2018), WHO (Import vom 15.04.2018)
Geändert: 13.02.2018
Krankheitskategorie: Anderes

Zusammenfassende Beschreibung der Studie (Datenquelle: BASEC)

Lo studio sarà condotto per rispondere a specifiche richieste dell’ufficio di qualità del prodotto (OPQ) dell’USA Food & Drug Administration (FDA) durante la fase di registrazione del prodotto. Lo studio prevede una visita preliminare ambulatoriale, detta di screening, un periodo di trattamento e una visita finale. I soggetti dovranno rimanere in clinica dal tardo pomeriggio del giorno -1 (giorno prima del trattamento) sino alla mattina del giorno 2. La durata del ricovero in clinica sarà in totale di un giorno e due notti. Lo studio avrà una durata minima di 4 giorni e massima di 23 a seconda di quanti giorni prima dell’applicazione verrà effettuata la visita di screening.

Untersuchte Krankheiten (Datenquelle: BASEC)

NA_Lo studio prevede di valutare l’adesività, a più tempi, del cerotto Flectoparin® Tissugel applicato per 24 ore su volontari sani di ambo i sessi

Health conditions (Datenquelle: WHO)

DHEP-medicated plaster
Skin and Connective Tissue Diseases
DHEP-medicated plaster

Seltene Krankheit (Datenquelle: BASEC)

Nein

Untersuchte Intervention (z.B. Medikament, Therapie, Kampagne) (Datenquelle: BASEC)

Durante lo studio saranno applicati contemporaneamente per 24 ore due cerotti medicati di Flectoparin® Tissugel (contenente diclofenac epolamina 181 mg ed eparina 5600 I.U.,già in commercio in svizzera) come segue: un cerotto senza rinforzo e uno cerotto con rinforzo, secondo una lista casuale, sul lato destro e sinistro della parte superiore della schiena (regione dorsale, sotto la scapola), con il lato più lungo parallelo alla colonna vertebrale. Per il rinforzo saranno applicati 4 certotti non medicati sui 4 angoli del cerotto medicato.Prima dell’applicazione e dopo la rimozione, saranno misurati i segni vitali (pressione arteriosa e frequenza cardiaca). Dopo 4, 8, 12, 16, 20 e 24 ore dall’applicazione il medico Sperimentatore valuterà l’adesività dei cerotti nei punti di applicazione. Prima dell’applicazione e negli stessi orari in cui verrà valutata l’adesività saranno scattate delle foto delle aree di applicazione e le aree di adesione o distaccamento saranno tracciate su lucidi.

Interventions (Datenquelle: WHO)

The study consists of a screening visit, a treatment phase of one study period and a final visit/early termination visit (ETV).
For each subject, two DHEP-Heparin medicated plasters are applied concurrently as follows: one plaster without reinforcement (PW) and one plaster with reinforcement (PR) are applied to the right and left side of the upper back (dorsal region, below the scapula), with the longer side parallel to the spine, at the same height, as near as possible to the spine. Plaster for PR treatment was reinforced using small pieces of tape applied to the four corners of the DHEP-Heparin plaster.

The investigator assesses each plaster adhesion at 4, 8, 12, 16, 20 and 24 h post-application using the following 5-point scale, according to the FDA Guidance for Assessing adhesion.

In addition, at each time point, when adhesion was assessed on the 5-point scale, the actual percentage adherence value (%) was estimated by the investigator and reported in the CRF.

The two assessments (score and actual percentage evaluation) are visually performed by a an experienced and trained scorer (the Principal Investigator) who was previously involved as investigator in several clinical trials where visual evaluation of patch detached area was part of study assessments.

Standardised digital photographs are taken before application and at each assessment time for each plaster.

After adhesion assessment and photograph, at each assessment time the shapes of attachment/detachment area of each plaster were traced on an acetate sheet in order to collect an additional image of the detached area of each plaster.

Each plaster contained 181 mg DHEP corresponding to 140 mg diclofenac sodium. Therefore, the subjects are exposed to a total dose of approximately 280 mg diclofenac sodium.

The randomisation list is computer-generated by the Department of Biometry at the Contract Research Organization (CRO) using the PLAN procedure of the validated SAS for Windows Version 9.1.3 Serv

Kriterien zur Teilnahme an der Studie (Datenquelle: BASEC)

- fornire il consenso prima dell’inclusione e prima che venga effettuata qualsiasi procedura prevista dallo studio;
- essere un uomo o una donna di età compresa tra i 18 e i 55 anni e con un indice di massa corporea compreso tra 18.5 kg/m2 e 30 kg/m2;
- avere segni vitali nei limiti della norma (ovvero pressione sistolica compresa tra 100 e 139 mmHg, diastolica compresa tra 50 e 89 mmHg e frequenza cardiaca compresa tra 50 e 90 battiti al minuto), misurati dopo 5 minuti di riposo in posizione seduta;
- essere in grado di comprendere completamente la natura e lo scopo dello studio che viene proposto, inclusi i possibili rischi ed eventi avversi ed essere in grado di collaborare con il medico Sperimentatore e di seguire le procedure previste durante tutta la durata dello studio;
- se è una donna in età fertile, deve utilizzare un metodo contraccettivo efficace, ovvero: contraccettivi ormonali (orali, impiantabili, transdermici e iniettabili) o contraccettivi non ormonali (spirali intrauterine, preservativi femminili, spugne contraccettive, diaframmi o cappucci cervicali con l’aggiunta di spermicida) a partire da almeno 2 mesi prima della visita di screening;
- partner vasectomizzati, o che usino il preservativo con l’aggiunta di spermicida. Il solo preservativo non è considerato un metodo di contraccezione adeguato;
- essere una donna sterile o in post-menopausa, da almeno un anno.

Ausschlusskriterien (Datenquelle: BASEC)

- riportare alterazioni clinicamente significative all’elettrocardiogramma;
- presentare alterazioni fisiche clinicamente significative che possano interferire con gli obiettivi dello studio;
- avere alterazioni clinicamente significative dei parametri di laboratorio, indicative di una condizione patologica concomitante;
- soffrire o aver sofferto di ipersensibilità presunta o accertata ai principi attivi (diclofenac epolamina e eparina) e/o agli eccipienti del prodotto, aver avuto una storia di anafilassi ai farmaci o reazioni allergiche in generale, che il medico Sperimentatore giudichi non compatibili con lo studio;
- avere una significativa storia di malattie renali, epatiche, gastrointestinali, cardiovascolari, respiratorie, cutanee, ematologiche, endocrine o neurologiche che possano interferire con lo svolgimento dello studio;
- soffrire di malattie della pelle, lesioni cutanee o ferite aperte sui siti d’applicazione;
- avere assunto farmaci, inclusi farmaci da banco (senza obbligo di prescrizione) e prodotti erboristici nelle 2 settimane precedenti l’inizio dello studio. I contraccettivi ormonali per le donne sono ammessi;
- aver partecipato ad altri studi sperimentali sui farmaci nei tre mesi precedenti l’inizio dello studio, calcolati partendo dal primo giorno del mese successivo all’ultima visita dello studio precedente;
- fare abuso di stupefacenti;
- fare abuso d’alcool (più di un bicchiere al giorno per le donne e più di 2 bicchieri al giorno per gli uomini);
- bere più di 5 tazze al giorno di bevande che contengono caffeina (quali caffè, tè);
- fumare 10 o più sigarette al giorno;
- seguire una dieta sbilanciata (<1.600 o >3.500 kcal/giorno) o avere avuto variazioni significative nelle abitudini alimentari nelle 4 settimane precedenti l’inizio di questo studio; essere vegetariano;
- risultare positiva al test per verificare l’assunzione dell’alcol, al test delle urine per l’identificazione di sostanze stupefacenti o al test di gravidanza.

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Inclusion criteria: 1. Informed consent: signed written informed consent before inclusion in the study
2. Sex and Age: males/females, 18-55 years old inclusive
3. Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
4. Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate (HR) 50-90 bpm, measured after 5 min at rest in the sitting position
5. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
6. Contraception and fertility (females only): females of child-bearing potential must be using at least one of the following reliable methods of contraception:
6.1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit
6.2. A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
6.3. A male sexual partner who agreed to use a male condom with spermicide
6.4. A sterile sexual partner
Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year are admitted. For all female subjects, pregnancy test result had to be negative at screening and at each scheduled evaluation.

Exclusion criteria: 1. Electrocardiogram (12-leads, supine position): clinically significant abnormalities
2. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
3. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
4. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considered could affect the outcome of the study
5. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that could interfere with the aim of the study
6. Application site: diseased-skin, skin wounds or open injuries at the applications site
7. Medications: medications, including over the counter medications and herbal remedies for 2 weeks before the start of the study. Hormonal contraceptives for females were allowed
8. Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval was calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study
9. Drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for females and >2 drinks/day for males, defined according to the USDA Dietary Guidelines 2015-2020], caffeine (>5 cups coffee/tea/day) or tobacco abuse (?10 cigarettes/day)
10. Drug test: positive result at the drug test at screening
11. Alcohol test: positive alcohol breath test at day -1
12. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians
13. Pregnancy (females only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women

Weitere Angaben zur Studie im WHO-Primärregister

http://isrctn.com/ISRCTN41927312

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN41927312

Weitere Informationen zur Studie

Registrationsdatum der Studie

20.12.2017

Einschluss der ersten teilnehmenden Person

12.12.2016

Rekrutierungsstatus

Completed

Wissenschaftlicher Titel (Datenquelle: WHO)

Adhesion study of Flectoparin® Tissugel following plaster application in healthy volunteers

Studientyp (Datenquelle: WHO)

Interventional

Design der Studie (Datenquelle: WHO)

Single-centre single-dose open-label one-period two-treatment randomised adhesion assessment study (Treatment)

Primäre Endpunkte (Datenquelle: WHO)

Adhesion score for the investigational plaster without reinforcement (PW) is measured the 5-point scale at 4, 8, 12, 16, 20 and 24 h post-application.

Sekundäre Endpunkte (Datenquelle: WHO)

Safety and general tolerability of the IMP were based on the following assessments:
Record of adverse events
Adverse events (AEs) were assessed throughout the study.

Vital signs
Subjects’ blood pressure and heart rate were measured by the investigator or his deputy after 5 min at rest in the sitting position at screening, on days 1-2 at pre-dose and 24 h post-application, and in case of ETV. The vital signs measurement at 24 h post-dose was considered as the final assessment.

Electrocardiograms
A 12-lead resting ECG was performed in supine position at screening and interpreted by the investigator.

Physical examination and body weight
A physical examination was performed at screening .Body weight, height and body mass index (BMI) were recorded at screening only. Subjects were weighed (kg) lightly clothed without shoes. BMI was calculated as weight [kg] / (height [m] squared).

Laboratory analysis
1. Routine haematology, blood chemistry and urinalysis laboratory tests were performed, under fasting conditions, at screening.
2. Haematology: leukocytes and leukocyte differential count (percentage and absolute values), erythrocytes, haemoglobin (conv. units), haemoglobin (IS units), haematocrit, MCV, MCH, MCHC, thrombocytes.

Blood Chemistry:
1. Electrolytes: sodium, potassium, calcium, chloride, inorganic phosphorus
2. Enzymes: alkaline phosphatase, ?-GT, AST, ALT
3. Substrates/metabolites: total bilirubin, creatinine, fasting glucose, urea, uric acid, total cholesterol, triglycerides
Proteins: total proteins

Serum pregnancy test (women only, at screening)

Urine analysis:
1. Urine chemical analysis (stick): pH, specific weight, appearance, colour, nitrites, proteins, glucose, urobilinogen, bilirubin, ketones, haematic pigments, leukocytes
2. Urine sediment (analysis performed only if positive): leukocytes, erythrocytes, flat cells, round cells, crystals, cylinders, mucus, bacteria
3. Urine pregnancy test (women only, on day -1).
4. erum virology: Hepatitis B (HBs antigen), Hepatitis C (HCV Antibodies), HIV 1/2 (HIV Ag/Ac combo).
A urine drug test was performed at the clinical centre at screening, using a urine multi-drug kit. The following drugs were assessed: cocaine, amphetamine, methamphetamine, cannabinoids (delta-9-tetrahydrocannabinol - THC), opiates and ecstasy.

Measurements of Primary and secondary variables
Primary variables:
Adhesion scores on a 5-point numerical scale (13), where score 0==90% adhered (essentially no lift off the skin), score 1==75% to <90% adhered (some edges only lifting off the skin), score 2==50% to <75% (less than half of the plaster lifting off the skin), score 3=>0% to <50% adhered (not detached, but more than half of the plaster lifting off the skin without falling off), score 4=0% adhered (plaster detached; completely off the skin) for PW.

Secondary variables:
1. Adhesion scores on the 5-point numerical scale, as detailed above, for PR application.
2. Assessment of plaster adherence as a percentage of total plaster area for both PW and PR application
3. Safety variables: treatment-emergent adverse events, vital signs (blood pressure, heart rate), laboratory parameters

Kontakt für Auskünfte (Datenquelle: WHO)

IBSA Institut Biochimique SA

Studiendurchführungsorte

Durchführungsorte in der Schweiz (Datenquelle: BASEC)

Arzo, CROSS Research Phase I Unit, Svizzera

Durchführungsländer (Datenquelle: WHO)

Switzerland

Kontakt für weitere Auskünfte zur Studie

Angaben zur Kontaktperson in der Schweiz (Datenquelle: BASEC)

Milko Radicioni
0041 91 640 44 50
milko.radicioni@croalliance.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Milko
Radicioni
CROSS Research S.A.Phase I Unit, Via F.A. Giorgioli 14

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

IBSA Institut Biochimique SA

Weitere Studienidentifikationsnummern

BASEC ID (Datenquelle: BASEC)

2016-01830

Secondary ID (Datenquelle: WHO)

Study CRO-PK-16-315 - Sponsor code 16CH-FHp12