Clinical Trials Register

Summary
EudraCT Number:	2012-002237-11
Sponsor's Protocol Code Number:	ARC
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-18
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

UK - MHRA

A.2

EudraCT number

2012-002237-11

A.3

Full title of the trial

Effectiveness of Adaptive Opioid Agonist Maintenance Pharmacotherapy and Behavioural Therapy for Opioid Use Disorder.

A.3.1

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

Additction Recovery Clinic (ARC) - Adaptive Maintenance Treatment for Opioid Use Disorder.

A.3.2

Name or abbreviated title of the trial where available

Addiction Recovery Clinic (ARC)

A.4.1

Sponsor's protocol code number

ARC

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	King's College London
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Action on Addiction
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	South London & Maudsley NHS Foundation Trust
B.5.2	Functional name of contact point	Michael Kelleher
B.5.3	Address:
B.5.3.1	Street Address	Lorraine Hewitt House, 12-14 Brighton Terrace
B.5.3.2	Town/ city	Brixton, London
B.5.3.3	Post code	SW9 8DG
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	004402032281500
B.5.5	Fax number	004402032281585
B.5.6	E-mail	michael.kelleher@slam.nhs.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	South London and Maudsley NHS Foundation Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Action on Addiction (UK Charity)
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	South London & Maudsley NHS Foundation Trust
B.5.2	Functional name of contact point	Michael Kelleher
B.5.3	Address:
B.5.3.1	Street Address	Lorraine Hewitt House, 12-14 Brighton Terrace
B.5.3.2	Town/ city	Brixton, London
B.5.3.3	Post code	SW9 8DG
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	004402032281500
B.5.5	Fax number	004402032281585
B.5.6	E-mail	michael.kelleher@slam.nhs.uk

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	Suboxone
D.2.1.1.2	Name of the Marketing Authorisation holder	RB Pharmaceuticals Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Suboxone
D.3.4	Pharmaceutical form	Sublingual tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Sublingual 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.3.9.4	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	8
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.3.9.4	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
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.3.9.4	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	2
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.3.9.4	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	0.5
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: 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.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Methadone hydrochloride
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	METHADONE HYDROCHLORIDE
D.3.9.1	CAS number	76-99-3
D.3.9.4	EV Substance Code	SUB08833MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	60 to 120
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

Opiate dependency disorder

E.1.1.1

Medical condition in easily understood language

Dependency on heroin

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

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 determine the clinical and cost effectiveness of a personalised behavioural intervention (PBI) compared to treatment-as-usual (TAU) at achieving heroin and cocaine abstinence and health economic outcomes after 12 weeks of PBI, among initially non-responsive patients enrolled in Opiate Substitution Treatment (methadone [MMT]; Suboxone [SMT] (according to clinical preference) in a specialist NHS addictions treatment centre.

E.2.2

Secondary objectives of the trial

A. Are there identical treatment retention and psychological therapy adherence rates between PBI and TAU arms of the study?
B. Are there identical heroin and cocaine craving, and other clinical functioning response profiles between the PBI and TAU arms?
C. What are the longer-term treatment and addiction recovery outcomes for patients receiving PBI and TAU over 5 years, and can biomarkers of differential clinical response be identified?

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

18 years of age or older (no upper limit, but generally <60yrs).
Is able to comprehend English to the extent required by the study protocol
Demonstrates verbal understanding of the study patient information material, is able to provide written consent, and can understand and confirm willingness to comply with the protocol.
Current diagnosis of opioid use disorder (dependence)
Current opioid tolerance
Prescribed either methadone or suboxone
Voluntarily seeking treatment for opioid dependence and able to attend the clinic as described in the protocol.
Lives in sufficiently stable accommodation in the community, with a personal phone
Can nominate at least one locator individual (e.g. a family member, friend or recovery mentor) with a verifiable address and a telephone number which we can call to assist as necessary with the arrangement of follow-up appointments.

E.4

Principal exclusion criteria

Clinically significant medical condition including but not limited to: uncontrolled hypertension; significant heart disease (including myocardial infarction in past 12 months); angina; or any serious, potentially life-threatening or progressive medical illness other than addiction that may compromise subject safety or study conduct; or any abnormality which, in the investigator’s judgment, is clinically significant.
Current criminal justice involvement with legal proceedings and, in the opinion of the Chief Investigator, is expected to fail to complete the study protocol due to incarceration or relocation from the centre’s catchment area.
Current (past 30 day) suicidal ideation/plan, or recent (past six months) suicidal ideation or suicide attempt.
Active, uncontrolled severe mental illness (e.g. psychosis, bipolar I disorder, schizoaffective disorder – addressed in routine admissions protocol) and/or a history or evidence of organic brain disease or dementia that would compromise the participant’s ability to comply with the study protocol.
Is not currently a participant in a research study or has been in CTIMP research study in the previous 4 months

E.5 End points

E.5.1

Primary end point(s)

At week 24 the proportion of patients who are categorised as responder or non-responder.
Responders report no use of heroin or cocaine during weeks 21-24 and submit no positive urine drug tests during weeks 21-24
Non-responders report use of heroin or cocaine during weeks 21-24 or submit a positive urine drug tests during weeks 21-24
At week 24 week the relative cost-effectiveness of trial treatments using:
EQ5D
AD-SUSD

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoint(s) of evaluation of this end point (max 800 characters)
At weeks 21- 24 after enrollment for urine drug tests and 24 weeks for the EQ5D and AD-SUSD

E.5.2

Secondary end point(s)

1. Treatment retention (i.e. days from first dose of OST to treatment exit or follow-up point using information help by the clinic’s electronic patient journey database).
2. Heroin and cocaine craving via Minnesota Cocaine [and heroin] Craving Scale (MCCS) and other scale ratings
3. An exploratory analysis of moderation and mediation of treatment response will be also undertake using the following measures:
 BPD
 BPAQ-S
 BIS-11
 MoCA
 TOP
 WSAS

E.5.2.1

Timepoint(s) of evaluation of this end point

after enrollment
1. at 24 weeks
2. weeks 4,8,12,14
3. weeks -10, -6, -3, 0, 4, 8, 12,14

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

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

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

Yes

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

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

E.8.9.2

In all countries concerned by the trial 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:

600

F.1.3

Elderly (>=65 years)

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

600

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)

Patients in methadone and suboxone arms who are abstaining from heroin and cocaine by the end of the first 10 weeks will be transferred to local primary health care setting for continued OST treatment or withdrawal managment with support from the LHH team and further evaluation of response at 24 weeks. Non responding patients who continue in the trial past 12 weeks will at 24 weeks be transferred to treatment as usual with continued opioid agonist maintence treatment or withdrawal managment.

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

2012-09-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-04-02

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