Clinical Trials Register

Summary
EudraCT Number:	2011-001903-10
Sponsor's Protocol Code Number:	OX51-002
National Competent Authority:	Finland - Fimea
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-07-09
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

Finland - Fimea

A.2

EudraCT number

2011-001903-10

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled, dose finding trial using sublingual alfentanil to alleviate pain associated with a prostate biopsy procedure

A.3.1

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

A study to learn about the effect of alfentanil for pain relief in patients undergoing prostate biopsy

A.4.1

Sponsor's protocol code number

OX51-002

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	Orexo AB
B.1.3.4	Country	Sweden
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	Orexo AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Orexo AB
B.5.2	Functional name of contact point	Director, Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Virdings allé 32A
B.5.3.2	Town/ city	Uppsala
B.5.3.3	Post code	75105
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46187808907
B.5.5	Fax number	+46187808888
B.5.6	E-mail	marie.gardmark@orexo.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	OX51-3
D.3.2	Product code	OX51-3
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	ALFENTANIL HYDROCHLORIDE
D.3.9.1	CAS number	69049-06-5
D.3.9.4	EV Substance Code	SUB00339MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	350
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALFENTANIL HYDROCHLORIDE
D.3.9.1	CAS number	69049-06-5
D.3.9.4	EV Substance Code	SUB00339MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	700
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Sublingual tablet
D.8.4	Route of administration of the placebo	Sublingual use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Pain associated with prostate biopsy.

E.1.1.1

Medical condition in easily understood language

Pain associated with prostate biopsy.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10004857
E.1.2	Term	Biopsy prostate
E.1.2	System Organ Class	10022891 - Investigations

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 evaluate the analgesic efficacy of sublingual alfentanil tablets in patients who undergo prostate biopsy

E.2.2

Secondary objectives of the trial

1.To evaluate the safety and tolerability of sublingual alfentanil tablets.
2.To evaluate the patients' sedation after administration of sublingual alfentanil tablets.
3.To evaluate the relationship between dose and analgesic efficacy of sublingual alfentanil tablets in patients who undergo prostate biopsy.
4.To evaluate the post-procedural pain.
5.To evaluate the patients' and clinicians' satisfaction with the pain treatment of the procedure.
6.To evaluate the need for rescue medication.
7.To evaluate the PK profile of the sublingual alfentanil tablets in the target patient population.
8.To evaluate the post-procedural recovery time.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Men 18 to 85 years of age at the time of eligibility at Visit 1.
2. Signed informed consent obtained.
3. Abnormal digital rectal examination and/or elevated total prostate-specific antigen (tPSA) value > 4.0 ng/mL or increased Prostate-Specific Antigen (PSA) velocity based on Investigator judgment for biopsy.
4. Body mass index (BMI) between 19.0 and 34.0 kg/m2 inclusive.

E.4

Principal exclusion criteria

1. Previous prostate biopsy.
2. Prior radiation therapy to pelvis.
3. Anal fissure, anal stricture or any other anorectal pathology that may interfere with the prostate biopsy procedure, as judged by the Investigator.
4. Suspected urinary tract infection or recent (within 30 days) active urological infection (e.g., prostatitis).
5. Any known hypersensitivity or contraindication to alfentanil, other opioids or local anaesthetics.
6. A history or presence of drug or alcohol abuse.
7. Concomitant or prior use of opioids within 2 weeks prior to IMP administration.
8. Concomitant or prior use of any analgesic treatment for pain within 24 hours prior to IMP administration.
9. Concomitant or prior use of any sedating medications (e.g. barbiturates, benzodiazepines, neuroleptics, antihistamines) within 24 hours prior to IMP administration.
10. Concomitant use of monoamine oxidase inhibitors (e.g. Aurorix/moklobemid).
11. Concomitant or prior use of medium to strong cytochrome P450 (CYP) 3A4 enzyme inhibitors or 3A4 enzyme inducers within 14 days prior to IMP administration (pre-biopsy administration of antibiotics according to site standard practice is allowed, except for clarithromycin, erythromycin, telithromycin and rifampin/rifampicin. See Appendix 13.2 for prohibited medications).
12. Bleeding diathesis.
13. Anticoagulant treatment (aspirin up to max 160 mg/day is allowed).
14. Chronic pain and/or need of chronic pain treatment.
15. Current pain as measured by a score of > 3 on an 11-items Numerical Rating Scale (NRS).
16. Severe airway and lung disease such as symptomatic asthma, chronic bronchitis, emphysema or sleep apnea syndrome.
17. A history of any seizure disorder (other than febrile seizures).
18. A history of significant liver or renal disease.
19. A history of hypothyreosis.
20. Clinically significant cardiac disease or central nervous system disease.
21. Clinically significant abnormality detected in the patient?s physical examination, vital signs (including clinically significant abnormal orthostatic blood pressure) or 12-lead ECG as judged by the investigator.
22. History and/or presence of any somatic disease/condition that may interfere with the objectives of the trial as judged by the Investigator.
23. Participation in any other trial involving an IMP within 3 months before assessment of eligibility at Visit 1.
24. Otherwise not suitable to participate in the trial in the opinion of the Investigator.

E.5 End points

E.5.1

Primary end point(s)

1. Worst pain intensity experienced during prostate biopsy measured immediately after end of prostate biopsy procedure by Numerical Rating Scale (NRS), Direction #2.

E.5.1.1

Timepoint(s) of evaluation of this end point

immediately after end of prostate biopsy procedure

E.5.2

Secondary end point(s)

1. AEs, ECGs, pulse rate, blood pressure, respiratory rate, oxygen saturation (measured by pulse oximetry (SpO2)) and visual inspection of the oral mucosa.

2a. Independent observer assessment of patient sedation by using Pasero Opioid-induced Sedation Scale (POSS) prior to Investigational Medicinal Product (IMP) administration, at 5-10 minutes after IMP administration and at 10, 30, 60, 90, 120 and 240 minutes after end of prostate biopsy procedure.

2b. Patient subjective assessment of sedation by using Patient Global Impression of Drowsiness (PGID) prior to IMP administration, at 5-10 minutes after IMP administration and at 10, 30, 60, 90, 120 and 240 minutes after end of prostate biopsy procedure.

3. Worst pain intensity experienced during prostate biopsy measured immediately after end of prostate biopsy procedure by NRS.

4. Pain intensity measured at 10, 30, 60, 90 and 240 minutes after end of prostate biopsy procedure, measured by NRS, Direction #3.

5. Patient Global Impression of Satisfaction (PGIS) and Clinician Global Impression of Satisfaction (CGIS) measured 90 minutes after end of prostate biopsy procedure.

6. Percentage of patients receiving rescue medication.

7. PK parameters

8. Recovery criteria by Aldrete score prior to IMP administration and at 10, 30, 60, 90, 120, 180 and 240 minutes after end of prostate biopsy procedure.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Measured during procedure
2a.prior to Investigational Medicinal Product (IMP) administration, at 5-10 minutes after IMP administration and at 10, 30, 60, 90, 120 and 240 minutes after end of prostate biopsy procedure.
2b.prior to IMP administration, at 5-10 minutes after IMP administration and at 10, 30, 60, 90, 120 and 240 minutes after end of prostate biopsy procedure.
3. immediately after end of prostate biopsy
4. measured at 10, 30, 60, 90 and 240 minutes after end of prostate biopsy procedure
5.90 minutes after end of prostate biopsy procedure.
6. after last patient/last visit.
7. after last patient/last visit.
8. prior to IMP administration and at 10, 30, 60, 90, 120 and 240 minutes after end of prostate biopsy procedure.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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

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:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

F.2 Gender

F.2.1

Female

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

200

F.4.2.2

In the whole clinical trial

200

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)

After trial patients will resume standard hospital care.

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

2012-08-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-08-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-06-04

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