Clinical Trials Register

Summary
EudraCT Number:	2014-003778-17
Sponsor's Protocol Code Number:	CHL.1/02-2014
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-11-21
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-003778-17

A.3

Full title of the trial

Spinal anaesthesia with Chloroprocaine HCl 1% for elective lower limb procedures of short duration: a prospective, randomised, observer-blind study in adult patients

Anestesia spinale con Cloroprocaina HCl 1% per interventi pianificati di breve durata agli arti inferiori: studio prospettico, randomizzato, in cieco per l’osservatore, su pazienti adulti

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Spinal anaesthesia with Chloroprocaine HCl 1% for elective lower limb procedures of short duration

Anestesia spinale con Cloroprocaina HCl 1% per interventi pianificati di breve durata agli arti inferiori

A.3.2

Name or abbreviated title of the trial where available

Chloroprocaine 1% - Spinal block

Cloroprocaina 1% - Blocco spinale

A.4.1

Sponsor's protocol code number

CHL.1/02-2014

A.5.4

Other Identifiers

Name:

Study

Number:

CRO-14-122

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sintetica S.A.
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sintetica S.A.
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CROSS S.A.
B.5.2	Functional name of contact point	Study Management
B.5.3	Address:
B.5.3.1	Street Address	Via F.A. Giorgioli 14
B.5.3.2	Town/ city	Arzo
B.5.3.3	Post code	6864
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	0041916300510
B.5.5	Fax number	0041916300511
B.5.6	E-mail	corporate@croalliance.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Decelex
D.2.1.1.2	Name of the Marketing Authorisation holder	L.Molteni § C. dei F.lli Alitti Società di Esercizio S.p.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Decelex (chloroprocaine HCl 1%[10 mg/mL])
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intrathecal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CHLOROPROCAINE HYDROCHLORIDE
D.3.9.1	CAS number	3858-89-7
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB01232MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Short duration (less than 40 min) lower limb surgery via spinal anaesthesia

indicazione per un intervento chirurgico di breve durata (inferiore a 40 minuti) agli arti inferiori, per mezzo di anestesia spinale

E.1.1.1

Medical condition in easily understood language

Short duration lower limb surgery via spinal anaesthesia

indicazione per un intervento chirurgico di breve durata (inferiore a 40 minuti) agli arti inferiori, per mezzo di anestesia spinale

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10041536
E.1.2	Term	Spinal anaesthesia
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective of this study is to evaluate the effect of 3 doses of Chloroprocaine HCl 1% (30, 40 and 50 mg) for spinal anaesthesia in adult patients undergoing short duration elective surgery of the lower limb, in terms of time to complete regression of spinal block

L’obiettivo di questo studio è valutare l’efficacia di tre differenti dosi di Cloroprocaina HCl 1% (30, 40 e 50 mg), utilizzata per l’anestesia spinale per interventi chirurgici di breve durata agli arti inferiori in pazienti adulti, in termini di tempo di completa regressione del blocco spinale

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of three Chloroprocaine HCl 1% doses in terms of Time to onset of sensory block and motor block, Time to readiness for surgery, Time to resolution of motor block and sensory block to S1, Time to unassisted ambulation, Sensory block metameric levels during the block, Maximum level of sensory block, Time to maximum level of sensory block, Time to regression of two dermatomers with respect to the maximum level of sensory block, Time to first spontaneous urine voiding, Time to administration of rescue anaesthesia or rescue analgesia, Time to first post-operative analgesia, Time to eligibility for home discharge, proportion of patients achieving effective anaesthesia, quality of spinal block; concentration of chloroprocaine and its metabolite 2-chloro-4-aminobenzoic acid (CABA) in plasma; excretion of the CABA in urine ; safety and tolerability of the administered Chloroprocaine HCl 1% doses

Efficacia delle tre differenti dosi di Cloroprocaina HCl 1% in termini di tempo di insorgenza del blocco sensoriale e motorio, momento in cui il paziente è pronto per l’intervento chirurgico, tempo di regressione del blocco motorio e del blocco sensoriale a S1, tempo alla deambulazione autonoma, livello metamerico del blocco sensoriale, livello massimo del blocco sensoriale e tempo al raggiungimento del livello massimo, tempo di regressione di due dermatomeri rispetto al livello massimo raggiunto, tempo alla prima minzione spontanea, tempo di somministrazione della “rescue” anestesia o analgesia, tempo di somministrazione della prima analgesia post operatoria, tempo al raggiungimento dei criteri di dimissibilità, proporzione di pazienti che raggiungono un’anestesia efficace, qualità del blocco spinale; concentrazioni plasmatiche della Cloroprocaina e del metabolita acido 2-cloro-4-amminobenzoico, escrezione urinaria dell’ acido 2-cloro-4-amminobenzoico; sicurezza e tollerabilità

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Sex, age and surgery: male/female patients, 18-80 years old, scheduled for short duration (less than 40 min) lower limb surgery requiring ≥ T12 metameric level of sensory block
2. Body Mass Index (BMI): 18 - 32 kg/m2 inclusive
3. ASA physical status: I-III
4. Informed consent: signed written informed consent before inclusion in the study

1. maschi o femmine con età compresa tra 18 e 80 anni, con indicazione per la chirurgia di breve durata (inferiore a 40 minuti) agli arti inferiori con un livello metamerico di blocco sensoriale > T12;
2. indice di massa corporea compreso tra 18 kg/m2 e 32 kg/m2;
3. classificazione I-III dello stato fisico secondo la Società Americana di Anestiologia (ASA);
4. firma del consenso informato scritto prima di qualsiasi procedura correlata allo studio;

E.4

Principal exclusion criteria

1. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study. Contraindications to spinal anaesthesia. History of neuromuscular diseases to the lower extremities
2. ASA physical status: IV-V
3. Further anaesthesia: patients expected to require further anaesthesia
4. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations ingredients; ascertained or presumptive hypersensitivity to the ester type and major anaesthetics
5. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study; ascertained psychiatric and neurological diseases, sepsis, blood coagulation disorders, severe cardiopulmonary disease, thyroid disease, diabetes or other neuropathies.
6. Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study, calculated from the first day of the month following the last visit of the previous study
7. Drug, alcohol: history of drug or alcohol abuse
8. Blood donation: blood donations in the 3 months before this study
9. Pregnancy and lactation: missing or positive pregnancy test at screening, pregnant or lactating women
10. Chronic pain syndromes: patients with chronic pain syndromes (taking opioids, antidepressants, anticonvulsant agents or chronic analgesic therapy)
11. Medications: medication known to interfere with the extent of spinal blocks for 2 weeks before the start of the study. Hormonal contraceptives for females are allowed.

1. alterazioni clinicamente significative delle condizioni fisiche che possano interferire con gli obiettivi dello studio. Controindicazioni all’anestesia spinale. Patologie neuromuscolari alle estremità inferiori;
2. classificazione IV/V dello stato fisico secondo la Società Americana di Anestiologia (ASA);
3. pazienti per cui si possa già prevedere la necessità di ulteriore anestesia;
4. ipersensibilità accertata o presunta al principio attivo e/o agli eccipienti dei farmaci in studio, agli esteri e ai principali anestetici;
5. malattie renali, epatiche, gastrointestinali, cardiovascolari, respiratorie, cutanee, ematologiche, endocrine o malattie neurologiche, che possano interferire con lo svolgimento dello studio; malattie psichiatriche e neurologiche accertate, sepsi, disturbi della coagulazione, patologie cardio-polmonari severe, malattie della tiroide, diabete o altre neuropatie;
6. Partecipazione ad altri studi clinici con farmaci sperimentali nei tre mesi precedenti l’inizio dello studio, calcolati partendo dal primo giorno del mese successivo all’ultima visita dello studio precedente;
7. uso di sostanze stupefacenti o abuso di bevande alcoliche;
8. donazioni di sangue nei tre mesi precedenti lo studio;
9. donne in gravidanza o in allattamento, test di gravidanza mancante o positivo allo screening;
10. pazienti con sindromi dolorose croniche (in trattamento con oppioidi, antidepressivi, agenti anticonvulsivi o in terapia analgesica);
11. uso, nelle due settimane precedenti lo studio, di farmaci che sono noti per interferire con l’estensione dell’anestesia spinale. I contraccettivi ormonali per le donne sono permessi.

E.5 End points

E.5.1

Primary end point(s)

To evaluate the efficacy of the three Chloroprocaine HCl 1% doses (i.e. 30 mg, 40 mg e 50 mg) in terms of time to complete regression of spinal block (i.e. end of anaesthesia)

Valutare l’efficacia delle tre differenti dosi di Cloroprocaina HCl 1% (30 mg, 40 mg e 50 mg) in termini di tempo di completa regressione del blocco spinale (cioè fine dell’effetto anestetico)

E.5.1.1

Timepoint(s) of evaluation of this end point

The evolution of spinal block will be evaluated before, during and after the surgery. Time to regression of spinal block is defined as the time when Bromage score returns to 0 and sensitive level returns to S2.

L'evoluzione del blocco spinale sarà valutata prima, durante e dopo l’intervento chirurgico. Il tempo di regressione del blocco spinale è definito come il momento in cui il punteggio secondo la scala di Bromage torna a 0 ed il livello sensitivo ritorna a S2.

E.5.2

Secondary end point(s)

To evaluate the efficacy of the three Chloroprocaine HCl 1% doses (30, 40 and 50 mg) in terms of Time to onset of sensory block, Time to onset of motor block, Time to readiness for surgery, Time to resolution of motor block, Time to unassisted ambulation, Time to resolution of sensory block to S1, Sensory block metameric levels during the block, Maximum level of sensory block, Time to maximum level of sensory block, time to regression of two dermatomers with respect to the maximum level of sensory block, Time to first spontaneous urine voiding, Time to administration of rescue anaesthesia or rescue analgesia, Time to first post-operative analgesia, Time to eligibility for home discharge, proportion of patients achieving an effective anaesthesia, quality of spinal block;
To assess the concentration of chloroprocaine and its metabolite 2-chloro-4-aminobenzoic acid (CABA) in plasma;
To assess the excretion of CABA in urine;
To investigate the safety and tolerability of the administered Chloroprocaine HCl 1% doses.

Valutare l’efficacia delle tre differenti dosi di Cloroprocaina HCl 1% (30 mg, 40 mg e 50 mg) in termini di tempo di insorgenza del blocco sensoriale, tempo di insorgenza del blocco motorio, momento in cui il paziente è pronto per l’intervento chirurgico, tempo di regressione del blocco motorio, tempo alla deambulazione autonoma, tempo di regressione del blocco sensoriale a S1, livello metamerico del blocco sensoriale durante il blocco, livello massimo del blocco sensoriale, tempo al raggiungimento del livello massimo di blocco sensoriale, tempo di regressione di due dermatomeri rispetto al livello massimo di blocco sensoriale raggiunto, tempo alla prima minzione spontanea, tempo di somministrazione della “rescue” anestesia o “rescue” analgesia, tempo di somministrazione della prima analgesia post operatoria, tempo al raggiungimento dei criteri di dimissibilità, proporzione di pazienti che raggiungono un’anestesia efficace, qualità del blocco spinale;
Valutare le concentrazioni plasmatiche della Cloroprocaina e del suo metabolita acido 2-cloro-4-amminobenzoico;
Valutare l’escrezione urinaria dell’ acido 2-cloro-4-amminobenzoico;
Valutare la sicurezza e tollerabilità della Cloroprocaina HCl 1%.

E.5.2.1

Timepoint(s) of evaluation of this end point

The evolution of sensory and motor blocks, including sensory block metameric level, will be evaluated every 2 min until readiness for surgery, every 5 min until the maximum level is reached (two consecutive observations with the same level of sensory block) and then every 5 min until regression of two dermatomers with respect to the maximum level of sensory block. After that, sensory and motor block assessments will be repeated every 30 min until regression of spinal block and complete regression of sensory block to S1 (if compatible with surgical procedure). Blood samples for PK analysis will be collected at baseline and at 5 10, 30 and 60 min after spinal puncture. Urine will be collected at the time of spontaneous voiding. Safety and tolerability will be assessed throughout the study.

L’evoluzione del blocco sarà valutato ogni 2 minuti fino al momento in cui il paziente sarà pronto per iniziare l’intervento, quindi ogni 5 minuti fino al raggiungimento del livello massimo del blocco sensoriale, e poi ogni 5 minuti fino alla regressione di due dermatomeri rispetto al livello massimo raggiunto. Poi le valutazioni del blocco sensoriale e motorio saranno ripetute ogni 30 minuti fino a regressione del blocco spinale e alla completa regressione del blocco sensoriale a S1 (se compatibile con la procedura chirurgica). Prelievi di sangue per la PK saranno raccolti al basale e a 5, 10, 30 e 60 minuti dopo la puntura spinale. Le urine saranno raccolte al momento della prima minzione spontanea dopo l’intervento. Sicurezza e tollerabilità saranno valutate durante tutto lo studio.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

con osservatore in cieco

observer blind

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

tre differenti dosi dell'IMP test

three different doses of test IMP

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

ultima visita dell'ultimo soggetto

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2014-11-21.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Nessuno

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-01-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-02-23

P. End of Trial
P.	End of Trial Status	Completed

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