Clinical Trials Register

Summary
EudraCT Number:	2013-001984-21
Sponsor's Protocol Code Number:	3/013/13
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2013-08-01
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

2013-001984-21

A.3

Full title of the trial

PRE-EMPT: Preventing Recurrence of Endometriosis by Means of long acting Protestogen Therapy

A.3.1

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

Preventing Recurrence of Endometriosis by means of long acting Protestogen Therapy

A.3.2

Name or abbreviated title of the trial where available

PRE-EMPT v1.0

A.4.1

Sponsor's protocol code number

3/013/13

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	University of Aberdeen & NHS Grampian
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	National Institute for Health Research (NIHR)
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	University of Aberdeen & NHS Grampian
B.5.2	Functional name of contact point	Dr Gail Holland
B.5.3	Address:
B.5.3.1	Street Address	Foresterhill House Annex
B.5.3.2	Town/ city	Foresterhill, Aberdeen
B.5.3.3	Post code	AB25 2ZB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01224 551123
B.5.5	Fax number	01224 550559
B.5.6	E-mail	G.Holland@abdn.ac.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	Mirena®
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer plc
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	Levonorgestrel releasing intra-uterine system
D.3.4	Pharmaceutical form	Intrauterine delivery system
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intrauterine use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Levonorgestrel
D.3.9.1	CAS number	797-63-7
D.3.9.4	EV Substance Code	AS1
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	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.3.11.13.1	Other medicinal product type	Levonorgestrel containing intrauterine system
D.IMP: 2
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	Depo-Provera
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer 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	Medroxyprogesterone acetate
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Medroxyprogesterone acetate
D.3.9.1	CAS number	71-58-9
D.3.9.4	EV Substance Code	AS5
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	over 3 months
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	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	Microgynon -30
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer PLC
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	Combine oral contraceptive pill containing levonorgestrel 150 mcg and Ethinylestradiol 30 mcg
D.3.4	Pharmaceutical form	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	Levonorgestrel
D.3.9.1	CAS number	797-63-7
D.3.9.4	EV Substance Code	AS3
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	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ethinylestradiol
D.3.9.1	CAS number	57-63-6
D.3.9.4	EV Substance Code	AS4
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	30
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Endometriosis

E.1.1.1

Medical condition in easily understood language

Endometriosis - identification of endometrial tissue outside of the endometrium

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10014778
E.1.2	Term	Endometriosis
E.1.2	System Organ Class	10038604 - Reproductive system and breast disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Main study principal objective To compare, in women undergoing conservative surgery for pain due to endometriosis, the effectiveness of some or all of the following four post-surgical treatment options in controlling the recurrence of symptoms and improving quality of life: 1) no treatment 2) levonorgestrel-releasing intra-uterine System (LNG IUS) 3) three monthly depot medroxyprogesterone acetate injections (DMPA) 4) the combined oral contraceptive pill (COC), dependent on the groups carried forward from the pilot.

E.2.2

Secondary objectives of the trial

Pilot study objectives: • To ascertain if randomising to one or more of the four treatment options will prove a barrier to overall recruitment, assess if a four-way randomisation is feasible and refine the research question. • To pilot and fine-tune study procedures, data capture forms and the assumptions around the sample size estimation • To understand which factors motivate women to agree to be randomised for follow up treatment following surgery for endometriosis • To explore barriers to recruitment to the trial Secondary clinical objectives: • To compare all four interventions in terms of pain relief, side-effects, acceptability, repeat surgery, recurrence of endometriotic ovarian cysts. Economic: • To compare the relative cost effectiveness of alternative hormonal interventions, DMPA injection, LNG-IUS,and combined contraceptive, to no hormonal treatment for the prevention of recurrent endometriosis. The main comparator will be no treatment but as with all decision a

E.2.3

Trial contains a sub-study

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A subset of women will also be asked to take part in the qualitative assessment of potential recruitment barriers during the pilot (first nine months) and then in the qualitative assessment of patient experience at one and three years.

E.3

Principal inclusion criteria

Investigators will be asked to confirm each eligibility criteria at randomisation. Inclusion Criteria: To be eligible for the PREEMPT Trial: • Women aged 16-45 • No immediate plans to conceive • Are scheduled to have laparoscopic conservative surgery, or a diagnostic laparoscopy with concurrent surgery if endometriosis is found, for pelvic pain associated with endometriosis. • (Pilot phase) willing to be randomised to at least one long acting progestogen (LNG-IUS/ DMPA) and either COCP or no treatment

E.4

Principal exclusion criteria

Any women, who at the point of randomisation, have any of the following are not eligible for the trial: • Current infertility (trying for a baby, receiving or contemplating fertility treatment) • Deep infiltrating endometriosis, involving the bowel or rectovaginal septum, and requiring complex surgery, whether pre-planned or identified at laparoscopy • Contraindications to the use of hormonal treatment with oestrogen or progestogens • Suspicion of malignancy

E.5 End points

E.5.1

Primary end point(s)

The primary outcome is the recurrence of symptoms as evaluated by the pain domain of the EHP-30 questionnaire at 36 months post-randomisation. The EHP-30 is a disease specific questionnaire to measure the health status of women with endometriosis. It demonstrates good reliability, validity, acceptability and responsiveness,with low floor and ceiling effects for the core questions. EHP-30 contains 30 core items with 5 scales, and six modular parts of 23 questions which are dependent on the woman’s circumstances e.g. impact on work, sexual activity and fertility. It will be assessed prior to randomisation and at 6, 12, 24 and 36 months.

E.5.1.1

Timepoint(s) of evaluation of this end point

EHP-30 will be collected prior to randomisation and at 6, 12, 24 and 36 months post-randomisation.

E.5.2

Secondary end point(s)

CLINICALEHP-30 The remaining four core domains of the EHP-30 (control, emotional aspects, social support and self-image) and the six modular domains (work, relationship with family, sexual intercourse, medical professions, treatment, infertility), where completed, will be compared between groups. Pain scores will be collected using visual analogue scales. Fatigue, as measured by Fatigue Severity Score (FSS) Use of dietary supplements, following a gluten free or otherwise restrictive diet, or are using complementary therapies such as acupuncture. Generic health related quality of life (EQ-5D) and capabilities (ICECAP-A)

E.5.2.1

Timepoint(s) of evaluation of this end point

Participant reported outcomes will be collected prior to randomisation and at 6, 12, 24 and 36 months post-randomisation.

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

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

No additional hormonal treatment

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

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

The end of the trial will be defined as when the final participant recruited reaches the 3 year follow-up timepoint. Due to the long-term nature of some of the interventions, participants may remain on treatment beyond the end of the trial, and will be cared for by the general practitioner as they would outside of the trial.

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

Yes

F.1.1