Clinical Trials Register

Summary
EudraCT Number:	2022-001358-41
Sponsor's Protocol Code Number:	VER-CLBP-002
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Temporarily Halted
Date on which this record was first entered in the EudraCT database:	2022-12-20
Trial 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

Spain - AEMPS

A.2

EudraCT number

2022-001358-41

A.3

Full title of the trial

Multicentre, randomized, open-label study to prove an additional benefit of the full-spectrum cannabis extract VER-01 over opioids in the treatment of patients with chronic non-specific low back pain.

Estudio multicéntrico, aleatorizado y abierto para demostrar un beneficio adicional del extracto de cannabis de espectro completo VER-01 sobre los opioides en el tratamiento de pacientes con lumbalgia inespecífica crónica.

A.3.1

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

Clinical study to prove that treatment of chronic (non-specific) low back pain with VER-01, a cannabis based medicine, shows benefit compared to treatment with opioids

Estudio clínico para probar que el tratamiento crónico (no específico) de lumbalgia con VER-01, un medicamento basado en cannabis muestra beneficios comparados con tratamientos con opioides.

A.3.2

Name or abbreviated title of the trial where available

ELEVATE

A.4.1

Sponsor's protocol code number

VER-CLBP-002

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	Vertanical GmbH
B.1.3.4	Country	Germany
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	Vertanical GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Vertanical GmbH
B.5.2	Functional name of contact point	Dr. Tobias Gruber
B.5.3	Address:
B.5.3.1	Street Address	Am Haag 14
B.5.3.2	Town/ city	Gräfelfing
B.5.3.3	Post code	82166
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49 89 7879790-148
B.5.6	E-mail	studienkoordination@vertanical.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	No
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	Standardized oleoresin of Cannabis sativa L. folium cum flore, THC-chemotype
D.3.2	Product code	VER-01
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Standardised oleoresin of Cannabis sativa L. folium cum flore, THC-chemotype (cannabis leaves and - flowers), cor. to 21 mg THC per gram drug product
D.3.9.1	CAS number	1972-08-3
D.3.9.2	Current sponsor code	VER-01
D.3.9.4	EV Substance Code	SUB06407MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	21
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
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	Yes
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Tramadol 100 mg prolonged-release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tramadol
D.3.9.1	CAS number	36282-47-0
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Tramadol hydrochloride
D.3.9.4	EV Substance Code	SUB11210MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Tramadol 200 mg prolonged-release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tramadol
D.3.9.1	CAS number	36282-47-0
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Tramadol hydrochloride
D.3.9.4	EV Substance Code	SUB11210MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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.IMP: 4
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Fentanyl 12 micrograms/h transdermal patch
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fentanyl
D.3.9.1	CAS number	437-38-7
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Not Applicable
D.3.9.4	EV Substance Code	SUB07597MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.063
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.IMP: 5
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Fentanyl 25 micrograms/h transdermal patch
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fentanyl
D.3.9.1	CAS number	437-38-7
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Not Applicable
D.3.9.4	EV Substance Code	SUB07597MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4.125
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.IMP: 6
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Fentanyl 50 micrograms/h transdermal patch
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fentanyl
D.3.9.1	CAS number	437-38-7
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Not Applicable
D.3.9.4	EV Substance Code	SUB07597MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8.25
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.IMP: 7
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Oxycodone 5 mg prolonged-release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxycodone
D.3.9.1	CAS number	76-42-6
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Oxycodone hydrochloride
D.3.9.4	EV Substance Code	SUB09562MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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.IMP: 8
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Oxycodone 20 mg prolonged-release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxycodone
D.3.9.1	CAS number	76-42-6
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Oxycodone hydrochloride
D.3.9.4	EV Substance Code	SUB09562MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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.IMP: 9
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Oxycodone & Naloxone (5 mg/2.5 mg) prolonged-release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxycodone
D.3.9.1	CAS number	76-42-6
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Oxycodone hydrochloride
D.3.9.4	EV Substance Code	SUB09562MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Naloxone
D.3.9.1	CAS number	465-65-6
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Naloxone Hydrochloride
D.3.9.4	EV Substance Code	SUB09142MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
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.IMP: 10
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Oxycodone & Naloxone (20 mg/10 mg) prolonged-release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxycodone
D.3.9.1	CAS number	76-42-6
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Oxycodone hydrochloride
D.3.9.4	EV Substance Code	SUB09562MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Naloxone
D.3.9.1	CAS number	465-65-6
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Naloxone Hydrochloride
D.3.9.4	EV Substance Code	SUB09142MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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.IMP: 11
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Hydromorphone 4 mg Prolonged Release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Hydromorphone
D.3.9.1	CAS number	466-99-9
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Hydromorphone hydrochloride
D.3.9.4	EV Substance Code	SUB08070MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
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.IMP: 12
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Hydromorphone 8 mg Prolonged Release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Hydromorphone
D.3.9.1	CAS number	466-99-9
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Hydromorphone hydrochloride
D.3.9.4	EV Substance Code	SUB08070MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8
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.IMP: 13
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Morphine 10 mg prolonged-release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Morphine
D.3.9.1	CAS number	57-27-2
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Morphine
D.3.9.4	EV Substance Code	SUB03332MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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.IMP: 14
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Morphine 20 mg prolonged-release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Morphine
D.3.9.1	CAS number	57-27-2
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Morphine
D.3.9.4	EV Substance Code	SUB03332MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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.IMP: 15
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Tapentadol 50 mg prolonged-release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tapentadol
D.3.9.1	CAS number	175591-23-8
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Tapentadol hydrochloride
D.3.9.4	EV Substance Code	SUB31821
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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.IMP: 16
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Tapentadol 100 mg prolonged-release tablets
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tapentadol
D.3.9.1	CAS number	175591-23-8
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Tapentadol hydrochloride
D.3.9.4	EV Substance Code	SUB31821
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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.IMP: 17
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Buprenorphine 5 µg/h Transdermal Patch
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Buprenorphine
D.3.9.1	CAS number	52485-79-7
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Not Applicable
D.3.9.4	EV Substance Code	SUB05985MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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.IMP: 18
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Buprenorphine 15 µg/h Transdermal Patch
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Buprenorphine
D.3.9.1	CAS number	52485-79-7
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Not Applicable
D.3.9.4	EV Substance Code	SUB05985MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
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.IMP: 19
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Buprenorphine 35 µg/h Transdermal Patch
D.3.2	Product code	Not Applicable
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Buprenorphine
D.3.9.1	CAS number	52485-79-7
D.3.9.2	Current sponsor code	Not Applicable
D.3.9.3	Other descriptive name	Not Applicable
D.3.9.4	EV Substance Code	SUB05985MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	35
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

Chronic non-specific low back pain

Lumbalgia inespecífica crónica

E.1.1.1

Medical condition in easily understood language

Back pain in between the lower edge of the ribs and the lower fold of the buttocks lasting for at least 3 months which has no specific identifiable cause

Dolor de espalda entre el borde inferior de las costillas y el pliegue inferior de las nalgas que dura al menos 3 meses y no tiene una causa identificable específica

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To prove a reduced risk of developing constipation under treatment with VER-01 compared to an opioid therapy at the end of treatment phase (visit 9)

Demostrar la reducción del riesgo de desarrollar estreñimiento en tratamiento con VER-01 en comparación con un tratamiento con opioides al final de la fase de tratamiento (visita 9).

E.2.2

Secondary objectives of the trial

Further evaluate the safety and tolerability of VER-01 compared to an opioid therapy
Compare efficacy of VER-01 to an opioid therapy

Evaluar más a fondo la seguridad y tolerabilidad de VER-01 en comparación con un tratamiento con opioides
Comparar la eficacia de VER-01 con un tratamiento con opioides

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female patients ≥18 years of age
2. Provision of informed consent form voluntarily signed and dated by the patient
3. For women of childbearing potential and men of reproductive potential: use of a reliable contraceptive method (Pearl index < 1) at least 1 month before the start of the study and willingness to use it during the study participation and 3 months after the last intake of the test or comparative intervention
4. Patient understands the local language and is willing and able to comply with scheduled visits, treatment plan, patient diary and other study related procedures throughout study participation
5. Chronic (for at least 3 months) non-specific pain in the lower back (between the 12th thoracic vertebra and lower gluteal folds). Non-specific pain refers to pain without a clear specific treatable cause.
6. Patients with indicated drug treatment* where previous optimized treatments** with non-opioid analgesics (including combinations) have not led to sufficient pain relief or were unsuitable due to contraindications or intolerance.
* Drug treatment is indicated if analgesic drug therapy is considered supportive for the realization of activating measures, or if the patient has unbearable functional disabilities as a result of the pain, despite regularly performing these measures.
** Treatment is considered optimized when
I. a further increased drug dose is unsuitable from a medical perspective considering side effects and/or
II. it is not expected that a higher drug dose would result in a further advantage in terms of efficacy.
7. Low back pain intensity on average at least 4 points on an 11-point Numeric Rating Scale in the last 4 weeks prior visit 1
8. Ongoing non-drug pain therapy (physical or behavioral therapy) must have been stable for at least 2 weeks prior visit 1 and must be continued during the run-in phase
9. Ongoing additional analgesic treatment prior visit 1 must be continued during the run-in phase
10. Bowel Function Index total score of 28.8 or less at visit 1.

1. Pacientes masculinos y femeninos ≥18 años de edad
2. Entrega del formulario de consentimiento informado firmado y fechado voluntariamente por el paciente.
3. Para las mujeres en edad fértil y los hombres con capacidad reproductiva: uso de un método anticonceptivo fiable (índice de Pearl <1) al menos 1 mes antes del inicio del estudio y voluntad de utilizarlo durante la participación en el estudio y 3 meses después de la última toma de la intervención de prueba o comparativa
4. El paciente entiende el idioma local y está dispuesto y es capaz de cumplir con las visitas programadas, el plan de tratamiento, el diario del paciente y otros procedimientos relacionados con el estudio durante su participación en el mismo.
5. Dolor crónico (durante al menos 3 meses) inespecífico en la zona lumbar (entre la 12.ª vértebra torácica y los pliegues glúteos inferiores). El dolor inespecífico se refiere al dolor sin una causa específica clara y tratable.
6. Pacientes con tratamiento farmacológico indicado* en los que los tratamientos optimizados** anteriores con analgésicos no opioides (incluidas las combinaciones) no han conducido a un alivio suficiente del dolor o no eran adecuados debido a contraindicaciones o intolerancia.
* El tratamiento farmacológico está indicado si el tratamiento farmacológico analgésico se considera de apoyo para la toma de las medidas activadoras, o si el paciente tiene una incapacidad funcional insoportable como consecuencia del dolor, a pesar de tomar regularmente estas medidas.** El tratamiento se considera optimizado cuando
I. no es adecuado seguir aumentando la dosis del fármaco desde la perspectiva médica, teniendo en cuenta los efectos secundarios y/o
II. no se espera que una dosis mayor del fármaco dé lugar a una mayor ventaja en cuanto a la eficacia.
7. Intensidad del dolor lumbar en una media de al menos 4 puntos en una escala de valoración numérica de 11 puntos en las últimas 4 semanas antes de la visita 1
8. El tratamiento del dolor no farmacológico en curso (tratamiento físico o conductual) debe haber sido estable durante al menos 2 semanas antes de la visita 1 y debe continuar durante la fase de preinclusión.
9. Durante la fase de preinclusión debe continuarse el tratamiento analgésico adicional en curso antes de la visita 1
10. Puntuación total del índice de función intestinal de 28,8 o menos en la visita 1.

E.4

Principal exclusion criteria

1. Patients with a known history of alcohol/drug/medication abuse or dependency and previous or current use of methadone
2. Evidence of drugs of abuse or illegal drugs by urine drug test performed at visit 1
3. Known intolerance or hypersensitivity to ingredients of rescue medication, opioid therapy (assigned by the investigator) and/or VER-01
4. Participation in another clinical interventional study within the last 30 days prior screening visit (visit 1)
5. Occupational groups with primary activity of operating machinery and driving motor vehicles
6. Planned blood donation or planned donation or freezing of sperm or oocytes during study participation and 3 months after end of study participation
7. Pregnant or breastfeeding female patients
8. Patient is unable to provide written informed consent, in need for care, has a guardian/caretaker, is immobile, or is particularly vulnerable (e.g., imprisoned; institutionalised by a court or judicial authority; dependent or employed by the sponsor, an external service provider of the sponsor (involved in the conduct of the study), the investigator or the trial site)
9. Known use of opioid or cannabis-based treatments within 30 days before screening visit (visit 1)
10. Patients for whom cannabis or opioid therapy is not indicated, e.g., due to a history of non-response to opioid therapy or cannabis-based medicines in the treatment of chronic non-specific low back pain in the past.
11. Start of or planned non-drug pain therapy during run-in phase (physical or behavioral therapy)
12. Start or planned start of an additional analgesic treatment during run-in phase
13. Ongoing monoamine oxidase inhibitor therapy at screening visit (visit 1)
14. Patients with history of cancer in the last 5 years prior to screening visit (visit 1). Except for cutaneous basal cell or squamous cell cancer resolved by excision without recurrence and cervical cancer in situ resolved by excision with negative pap test.
15. Painful comorbidities which could interfere with the low back pain intensity assessment during the study
16. Known history of human immunodeficiency virus (HIV) infection
17. Severe forms of the following diseases: Anaemia, haematological / autoimmune / endocrine / renal / hepatic / respiratory / cardiovascular / neurological / gastrointestinal / symptomatic peripheral vascular diseases.
18. Cardiovascular event in the last three months before screening visit (visit 1)
19. Known uncontrolled hypertension (average systolic blood pressure ≥140 mmHg or average diastolic blood pressure ≥90 mmHg) and/or untreated hypothyroidism
20. Patients with Crigler-Najjar syndrome, Rotor syndrome and/or porphyria
21. History of major trauma or back surgery in the last 2 months prior to screening visit (visit 1)
22. Known history of or current severe psychiatric illness
23. Known history of or current severe depression (not due to chronic low back pain) (assessed by Patient Health Questionnaire – 9) and/or suicidal ideation (assessed by Columbia-Suicide Severity Rating Scale) at screening visit (visit 1)
24. Patients with severe respiratory depression
25. Patients with lung disease associated with impaired lung function (e.g., acute or severe bronchial asthma or hypercapnia/respiratory failure).
26. Patients with conditions of increased intracranial pressure due to head injury or disease of the brain.
27. Patients with existing or suspected paralytic ileus
28. Patients with intestinal obstruction due to intestinal paralysis

1. Pacientes con un historial conocido de abuso o dependencia de alcohol/drogas/medicamentos y uso previo o actual de metadona.
2. Evidencia de abuso de medicamentos o consumo de drogas ilegales en un análisis de drogas en orina realizado en la visita 1.
3. Intolerancia o hipersensibilidad conocida a los ingredientes de la medicación de rescate, al tratamiento con opioides (asignado por el investigador) y/o al VER-01.
4. Participación en otro estudio clínico intervencionista en los 30 días anteriores a la visita de selección (visita 1).
5. Grupos profesionales cuya actividad principal es el manejo de maquinaria y la conducción de vehículos a motor.
6. Donación de sangre planificada o donación o congelación de esperma u óvulos planificada durante la participación en el estudio y 3 meses después de finalizar la participación en el estudio.
7. Pacientes embarazadas o en periodo de lactancia.
8. El paciente no puede dar su consentimiento informado por escrito, necesita cuidados, tiene un tutor/cuidador, está inmóvil o es especialmente vulnerable (por ejemplo, está encarcelado;
institucionalizado por un tribunal o una autoridad judicial; depende o está empleado por el promotor, un proveedor de servicios externo del promotor (que participa en la realización del estudio), el investigador o el centro del estudio).
9. Uso conocido de opioides o tratamientos basados en cannabis en los 30 días anteriores a la visita de selección (visita 1).
10. Pacientes para los que no está indicado el tratamiento con cannabis u opioides, por ejemplo, debido a un historial de falta de respuesta al tratamiento con opioides o medicamentos a base de cannabis en el tratamiento del dolor lumbar crónico inespecífico en el pasado.
11. Inicio o planificación de un tratamiento del dolor no farmacológico durante la fase de preinclusión (tratamiento físico o conductual).
12. Inicio o previsión de inicio de un tratamiento analgésico adicional durante la fase de preinclusión.
13. Tratamiento en curso con inhibidores de la monoaminoxidasa en la visita de selección (visita 1).
14. Pacientes con antecedentes de cáncer en los 5 años anteriores a la visita de selección (visita 1). Excepto el cáncer cutáneo de células basales o de células escamosas resuelto por escisión sin recidiva y el cáncer de cuello de útero in situ resuelto por escisión con citología negativa.
15. Comorbilidades dolorosas que podrían interferir con la evaluación de la intensidad del dolor lumbar durante el estudio.
16. Antecedentes conocidos de infección por el virus de la inmunodeficiencia humana (VIH).
17. Formas graves de las siguientes enfermedades: Anemia, enfermedades hematológicas / autoinmunes / endocrinas / renales / hepáticas / respiratorias / cardiovasculares / neurológicas /
gastrointestinales / vasculares periféricas sintomáticas.
18. Acontecimiento cardiovascular en los últimos tres meses antes de la visita de selección (visita 1).
19. Hipertensión no controlada conocida (presión arterial sistólica media ≥ 140 mmHg o presión arterial diastólica media ≥ 90 mmHg) y/o hipotiroidismo no tratado.
20. Pacientes con síndrome de Crigler-Najjar, síndrome de Rotor y/o porfiria.
21. Antecedentes de traumatismos importantes o de cirugía de la espalda en los últimos 2 meses anteriores a la visita de selección (visita 1).
22. Antecedentes conocidos de enfermedad psiquiátrica grave o enfermedad psiquiátrica grave actual.
23. Antecedentes conocidos de depresión grave o depresión grave actual (no debida a lumbalgia crónica) (evaluada por el Cuestionario de salud del paciente - 9) y/o ideación suicida (evaluada por la Columbia-Suicide Severity Rating Scale) en la visita de selección (visita 1).
24. Pacientes con depresión respiratoria grave.
25. Pacientes con enfermedad pulmonar asociada a un deterioro de la función pulmonar (por ejemplo, asma bronquial aguda o grave o hipercapnia/insuficiencia respiratoria).
26. Pacientes con afecciones de aumento de la presión intracraneal por traumatismo craneoencefálico o enfermedad cerebral.
27. Pacientes con presencia o sospecha de íleo paralítico.
28. Pacientes con obstrucción intestinal debida a parálisis intestinal.

E.5 End points

E.5.1

Primary end point(s)

Number and proportion of constipation responders at the end of treatment phase (visit 9). A constipation responder is defined as a patient with
1. a change from baseline (visit 2) in Bowel Function Index (BFI) total score of at least 15 points at visit 9 and
2. a BFI total score of more than 28.8 at visit 9.

Número y porcentaje de pacientes que responden al tratamiento en relación con el estreñimiento al final de la fase de tratamiento (visita 9).
Un paciente que responde en cuanto al estreñimiento se define como un paciente con
1. un cambio con respecto al inicio (visita 2) en la puntuación total del índice de función intestinal (Bowel Function Index, BFI) de al menos 15 puntos en la visita 9 y
2. una puntuación total del BFI de más de 28,8 en la visita 9.

E.5.1.1

Timepoint(s) of evaluation of this end point

visit 9

E.5.2

Secondary end point(s)

1. Number and percentage of 30% pain responders at study week 27 (last week of treatment phase) compared with the baseline score (study week -1)
2. Number and percentage of 30% pain responders in the subgroup of patients with a neuropathic pain component (painDETECT score > 18) at study week 27 compared with the baseline score (study week -1)
3. Number and percentage of patients with a 30% improvement of the mean daily low back pain interference with sleep score evaluated on an 11-point Numeric Rating Scale (NRS) at study week 27 compared with the baseline score (study week -1)

1. Número y porcentaje de personas que responden en cuanto al dolor en un 30 % en la semana 27 del estudio (última semana de la fase de tratamiento) en comparación con la puntuación inicial (semana -1 del estudio)
2. Número y porcentaje de pacientes que responden en cuanto al dolor en un 30 % en el subgrupo de pacientes con un componente de dolor neuropático (puntuación de painDETECT > 18) en la semana 27 del estudio en comparación con la puntuación inicial (semana de estudio -1)
3. Número y porcentaje de pacientes con una mejora del 30 % en la puntuación media del dolor lumbar diario que interfiere con el sueño, evaluada en una escala de valoración numérica (EVN) de 11 puntos, en la semana de estudio 27, en comparación con la puntuación inicial (semana de estudio -1).

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 27

Semana 27

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Última visita del último paciente.

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

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:

280

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

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.4.2

For a multinational trial

F.4.2.1

In the EEA

350

F.4.2.2

In the whole clinical trial

350

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

Ninguno

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

2023-04-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-03-22

P. End of Trial
P.	End of Trial Status	Temporarily Halted

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