Clinical Trials Register

Summary
EudraCT Number:	2012-003560-49
Sponsor's Protocol Code Number:	MD2012/01XP
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:	2012-08-28
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2012-003560-49

A.3

Full title of the trial

A PHASE II, RANDOMISED, SINGLE CENTRE, OPEN-LABEL, TWO-ARM STUDY TO DETERMINE THE SAFETY AND EFFICACY OF BUPRENORPHINE ORAL LYOPHILISATE (XPRENOR ®) IN COMPARISON WITH BUPRENORPHINE SUBLINGUAL TABLETS (SUBUTEX®)IN OPIOID-DEPENDENT PATIENTS

A.3.1

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

Safety & Efficacy of 2 Alternative Forms of Oral Buprenorphine (v10)

A.3.2

Name or abbreviated title of the trial where available

Safety & Efficacy of 2 Alternative Forms of Oral Buprenorphine (v10)

A.4.1

Sponsor's protocol code number

MD2012/01XP

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	Macarthys Laboratories Limited (trading as Martindale Pharma)
B.1.3.4	Country	United Kingdom
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	Macarthys Laboratories Limited (trading as Martindale Pharma)
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	Macarthys Laboratories Limited (trading as Martindale Pharma)
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Bampton Road, Harold Hill
B.5.3.2	Town/ city	Romford, Essex
B.5.3.3	Post code	RM3 8UG
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44(0)1277 23 5300
B.5.5	Fax number	+44(0)1277 84 8976
B.5.6	E-mail	tonyfisherlobro@gmail.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	Xprenor
D.3.4	Pharmaceutical form	Oral lyophilisate
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	Buprenorphine hydrochloride
D.3.9.1	CAS number	53152-21-9
D.3.9.3	Other descriptive name	BUPRENORPHINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB13133MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2 to 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: 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.2.1.1.1	Trade name	Subutex
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	Subutex 2 mg sublingual tablets and Subutex 8 mg sublingual tablets
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 hydrochloride
D.3.9.1	CAS number	53152-21-9
D.3.9.3	Other descriptive name	BUPRENORPHINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB13133MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2 to 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.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

Opioid dependency

E.1.1.1

Medical condition in easily understood language

Opioid dependency

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10001125
E.1.2	Term	Addiction
E.1.2	System Organ Class	100000004873

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 address the safety concerns of oral lyophilisate (an oral wafer) buprenorphine vs sublingual tablets as requested by MHRA. This is undertaken by direct comparision of the pharmacokinetic data and monitoring of several safety signals, primarily the markers of respiratory depression.

E.2.2

Secondary objectives of the trial

To also confirm efficacy versus a licenced comparator product containing the same active ingredient (buprenorphine)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Clinical condition: Opioid-dependent patients, eligible for opioid substitution therapy.
2. Gender: Male and Female.
3. Age: ≥18 - ≤60 years.
4. BMI: ≥18.0 to ≤30.0 Kg/m2.
5. Capable of providing voluntary informed consent.
6. For female subjects of child-bearing potential an adequate form of contraception must be adhered to for at least 30 days prior to trial entry however, this requirement may be waived if there have been two negative serum pregnancy tests at least seven days apart before being dosed with buprenorphine (e.g. at screening and prior to the first buprenorphine dose). The patient must adhere to a contraceptive regimen continuously until 30 days after the last Extension Period visit.
Adequate contraception is defined as:
a. The usage by the female subject/partner of any hormonal contraception or intra-uterine device (which should be established prior to the start of the trial), plus usage by at least one of the partners of an additional spermicide-containing barrier method of contraception.
b. The use of a barrier method alone or abstinence is not considered adequate.
c. Females of non-child-bearing potential i.e., postmenopausal, must be amenorrhoeic for at least 2 years AND have a serum follicle stimulating hormone (FSH) level of at least 30 IU/L, or have undergone a hysterectomy or bilateral oophorectomy (tubal ligation is not acceptable).
7. A non-custodial stable residence and telephone number.
8. For patients enrolling in the pharmacokinetic part of the study venous access must be suitable for the collection of serial blood samples. All other subjects should have venous access adequate for the collection of all required study samples using conventional techniques.
9. No treatment with either buprenorphine or methadone within one day of receiving study treatment. If potential study subjects do not meet this criterion patients can enter a Pre-randomisation Management Period. During this period buprenorphine and methadone will be excluded for at least one day. Where necessary, interim treatment with oral morphine (either as slow-release or standard oral immediate release morphine) will be provided.
10. The screening ECG should be normal or have no clinically significant abnormalities.

E.4

Principal exclusion criteria

1. Hypersensitivity to buprenorphine or any other component of the oral lyophilisate.
2. Dependent use of cocaine and amphetamines requiring specific treatment
3. .Regular use of other opioids from 24 hours prior to the first dose of buprenorphine until the end of the study.
4. Severe hepatic insufficiency (defined as liver function tests, including alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, greater than three times the upper limit of normal).
5. Patients suffering from severe respiratory insufficiency.
6. Patients suffering from acute alcoholism or delirium tremens.
7. Habitual or dependent use of benzodiazepines, which may potentiate respiratory depression, above recommended therapeutic doses or patients who are taking benzodiazepines erratically.
8. Concomitant medication known to interact with buprenorphine.
9. Administration of any approved or investigational long-acting injections of antipsychotic medications.
10. Current psychiatric diagnosis of major depression with suicidal ideation, psychosis, bipolar disorder, or any psychiatric disorder that would compromise the patient's ability to complete the study.
11. Female patients with a positive pregnancy test, lactating mother, women refusing to agree to adequate contraception and pregnancy tests during the study, or women who are planning to become pregnant during the period of the trial.
12. Participation in a clinical trial of a pharmacological agent within 6 months of screening.
13. Any other factor that in the opinion of the Investigator would make the patient unsafe or unsuitable for the study.

E.5 End points

E.5.1

Primary end point(s)

Safety:
1. Potential Oxygen desaturation (by pulse oximetry)
2. Respiration rate
3. Incidence of AE’s

Pharmacokinetics:
1. Cmax and Tmax in opioid dependent patients

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety:
1.Oximetry - at baseline and at time points during 3 hours following each increase in dose.
2.Respiration rate - at the same time points as oximetry.
3.Adverse events (AEs)s - throughout the study

E.5.2

Secondary end point(s)

Efficacy:
1. Opioid withdrawal symptoms
2. Scores on the Objective and Subjective Opioid Withdrawal Scales
3. Mean abuse liability score
4. Satisfaction of treatment (Likert scale)
5. Time required for (a) disintegration of the test medications and (b) complete disappearance, when placed in the therapeutic area of administration

E.5.2.1

Timepoint(s) of evaluation of this end point

For opioid withdrawal symptoms from baseline to end of study - OOWS, SOWS and Likert satisfaction scales scored in the one hour period before each dosing point.

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

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)

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

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)

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

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

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 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)

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.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)

No other additional care of study patients will take place by the study investigators following completion of the study and the treatment of the patient's condition wil follow standard clinical practice and will be provided by the patient's local treatment service of origin.

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

2012-10-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-12-23

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials