Clinical Trials Register

Summary
EudraCT Number:	2012-002215-26
Sponsor's Protocol Code Number:	M13-563
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-03-15
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2012-002215-26

A.3

Full title of the trial

A Double-Blind, Double-Dummy, Randomized, Two-arm, Multicenter Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg daily versus Intravaginal Micronized Progesterone Capsules 600 mg daily for Luteal Support in In-Vitro Fertilization

A.3.1

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

A study to compare if 30mg of oral Dydrogesterone is as good, tolerable and safe as 600mg of intravaginal capsules for luteal support in IVF pregnancies. This study will be conducted at several study sites and neither the patient or the doctor will know which of the two different treatments a patient will receive.

A.3.2

Name or abbreviated title of the trial where available

Lotus I

A.4.1

Sponsor's protocol code number

M13-563

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	Abbott Laboratories 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	Abbott Laboratories 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	Quintiles GmbH
B.5.2	Functional name of contact point	Simone Schicker
B.5.3	Address:
B.5.3.1	Street Address	Hugenottenallee 167
B.5.3.2	Town/ city	Neu-Isenburg
B.5.3.3	Post code	63263
B.5.3.4	Country	Germany
B.5.4	Telephone number	+496102 296 213
B.5.5	Fax number	+496102296296
B.5.6	E-mail	simone.schicker@quintiles.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	Yes
D.2.1.1.1	Trade name	Duphaston 10 mg comprimés pelliculés
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Products S.A.-N.V
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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.3.4	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	DYDROGESTERONE
D.3.9.1	CAS number	152-62-5
D.3.9.4	EV Substance Code	SUB06433MIG
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: 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	Utrogestan
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratoires BESINS INTERNATIONAL
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.3.4	Pharmaceutical form	Vaginal capsule, soft
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Vaginal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	micronised progesterone
D.3.9.1	CAS number	9002-68-0
D.3.9.3	Other descriptive name	PROGESTERONE, MICRONISED
D.3.9.4	EV Substance Code	SUB45084
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.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	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Vaginal capsule, soft
D.8.4	Route of administration of the placebo	Vaginal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Female infertility

E.1.1.1

Medical condition in easily understood language

Female inability to conceive a child

E.1.1.2

Therapeutic area

Body processes [G] - Reproductive physiologi cal processes [G08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10003540
E.1.2	Term	Assisted fertilization
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to demonstrate non-inferiority of oral dydrogesterone 10 mg TID versus micronized progesterone vaginal capsules 200 mg TID. The primary efficacy parameter is the presence of fetal heart beats at 12 weeks’ gestation determined by transvaginal ultrasound.

E.2.2

Secondary objectives of the trial

The secondary objectives and parameters are a positive pregnancy test on Day 14 after embryo transfer, the incidence of live births and healthy newborns.
The safety objective is to obtain safety and tolerability data by means of documentation of treatment emergent adverse events (TEAE) during the entire study period. In addition, data on vital signs, physical examination findings, and routine laboratory values will be obtained. Furthermore, signs and symptoms of threatened abortion, the rate of hypospadias and the rate of masculinization in female babies will be recorded. The time of delivery (pregnancy week) and the following parameters of the newborn will be obtained at delivery: gender, APGAR Score, weight, height, head circumference, abnormal findings of physical examination and any malformations.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent;
2. Premenopausal females, age > 18 years < 42 years
3. Non-smokers. For females who were past smokers, they must have stopped tobacco usage for at least 3 months prior baseline visit
4. Early follicular phase (Day 2-4) FSH (Follicle stimulating hormone) less than or equal to 15 IU/L and estradiol (E2)within normal limits
5. LH (luteinizing hormone), PRL (prolactin), T (testosterone) and TSH (thyroid-stimulating hormone), within the normal limits for the clinical laboratory, or considered not clinically significant by the Investigator within 6 months prior to screening
6. Documented history of infertility (e.g., unable to conceive for at least one year or for 6 months for women ≥ 38 years of age or bilateral tubal occlusion or absence)
7. Normal transvaginal ultrasound at screening (or within 14 days of screening) without evidence of clinically significant abnormality consistent with finding adequate for ART with respect to uterus and adnexa (no hydrosalpinx or clinically relevant uterine fibroids)
8. Negative pregnancy test on the day of pituitary down regulation (prior to administration of GnRH agonist or GnRH antagonist)
9. Clinically indicated protocol for induction of IVF with a fresh embryo
10. Single or dual embryo transfer
11. BMI ≥ 18 and ≤ 30 kg/m2

E.4

Principal exclusion criteria

1. Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematologic/immunologic, HEENT (head, ears, eyes, nose, throat), dermatologic/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurologic/psychiatric, allergy, recent major surgery (< 3 months), or other relevant diseases as revealed by history, physical examination and/or laboratory assessments which could limit participation in or completion of the study;
2. Acute urogenital disease
3. Known allergic reactions to progesterone products
4. Known allergic reactions to peanuts and peanut oil
5. Intake of experimental drug or participation in any other clinical trial within 30 days prior to study start
6. Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subjects to participate in or to complete the study
7. Current or recent substance abuse, including alcohol and tobacco (Note: Patients who stopped tobacco usage at least 3 months prior to screening visit would be allowed)
8. History of chemotherapy or radiotherapy
9. Patients with more than 3 unsuccessful IVF attempts
10. Contraindication for pregnancy
11. Refusal or inability to comply with the requirements of the study protocol for any reason, including scheduled clinic visits and laboratory tests
12. History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy parameter is the pregnancy rate defined as the presence of fetal heart beats at 12 weeks’ gestation determined by transvaginal ultrasound.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks’ gestation

E.5.2

Secondary end point(s)

The secondary parameters are a positive pregnancy test on Day 14 after embryo transfer, the incidence of live births and healthy newborns.
Further secondary parameters are gender and APGAR score as well as the height, weight and head circumference of the newborn (s).
In addition, a physical examination of the newborn will be performed and any malformations will be recorded.

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 14 after embryo transfer and birth

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)

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)

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Austria

Belgium

India

Israel

Russian Federation

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

End of Study is defined as Last Subject Last Visit

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:

1066

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

Yes

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

590

F.4.2

For a multinational trial

F.4.2.1

In the EEA

705

F.4.2.2

In the whole clinical trial

1066

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

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

2013-04-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-09-06

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