Clinical Trials Register

Summary
EudraCT Number:	2012-000123-41
Sponsor's Protocol Code Number:	B3D-EW-GHDW
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-03
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-000123-41

A.3

Full title of the trial

Teriparatide and Risedronate in the Treatment of Patients with Severe Postmenopausal Osteoporosis: Comparative Effects on vertebral Fractures

Teriparatide e Risedronato nel trattamento di pazienti con osteoporosi severa postmenopausale: comparazione degli effetti sulle fratture vertebrali

A.3.1

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

A study in postmenopausal women with severe osteoporosis to compare the effects of two osteoporosis drugs (Teriparatide and Risedronate) on fractures of the spine

Studio che coinvolge donne in postmenopausa con osteoporosi severa per comparare gli effetti di due farmaci per l'osteoporosi (Teriparatide e Risedronato)sulle fratture vertebrali

A.4.1

Sponsor's protocol code number

B3D-EW-GHDW

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	ELI LILLY
B.1.3.4	Country	Italy
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	Eli Lilly and Company Limited
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	Eli Lilly and Company Limited
B.5.2	Functional name of contact point	Sophie Laribiere
B.5.3	Address:
B.5.3.1	Street Address	Erl Wood Manor, Sunninghill Road
B.5.3.2	Town/ city	Windlesham
B.5.3.3	Post code	GU20 6PH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 1276 484870
B.5.5	Fax number	+44 1276 483378
B.5.6	E-mail	laribiere_sophie@lilly.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	Forteo
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TERIPARATIDE
D.3.9.1	CAS number	52232-67-4
D.3.9.2	Current sponsor code	LY333334
D.3.9.4	EV Substance Code	SUB10925MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	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	Risedronato
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Film-coated 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	RISEDRONATE SODIUM
D.3.9.1	CAS number	115436-72-1
D.3.9.2	Current sponsor code	Risedronate
D.3.9.4	EV Substance Code	SUB04252MIG
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	35
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	Injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Postmenopausal women with established osteoporosis and at least two moderate or one severe prevalent fragility fracture.

Donne in post-menopausa con osteoporosi e almeno due fratture moderate o una severa.

E.1.1.1

Medical condition in easily understood language

Postmenopausal women with severe osteoporosis and presence of fracture in spine

Donne in postmenopausa con osteoporosi severa e la presenza di fratture vertebrali

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	LLT
E.1.2	Classification code	10031288
E.1.2	Term	Osteoporosis with fracture
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue 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

The primary objective of this study is to evaluate if teriparatide 20 μg subcutaneously once daily is superior in reducing the incidence of new vertebral fractures during 24 months of therapy, when compared with risedronate 35 mg orally once weekly, in postmenopausal women with prevalent vertebral fragility fractures.

L'obiettivo primario dello studio è valutare se la somministrazione giornaliera di teriparatide per iniezione sottocutanea alla dose di 20 mcg riduce l'incidenza di nuove fratture vertebrali durante i 24 mesi di terapia, quando comparata con la somministrazione settimanale di risedronato orale alla dose di 35 mg, in donne in postmenopausa con fratture vertebrali.

E.2.2

Secondary objectives of the trial

The key secondary objectives of this study are to evaluate if teriparatide 20 μg/day is superior in reducing the incidence of the following key outcomes during 24 months of therapy, when compared with risedronate 35 mg/week: 1. Incidence of pooled new and worsening vertebral fractures. 2. Incidence of pooled clinical fractures. 3. Incidence of non-vertebral fragility fractures. 4. Incidence of major non-vertebral fragility fractures: hip, radius, humerus, ribs, pelvis and ankle.

Gli obiettivi secondari dello studio sono valutare se la somministrazione giornaliera di teriparatide per iniezione sottocutanea alla dose di 20 mcg, quando comparata con la somministrazione settimanale di risedronato orale alla dose di 35 mg,è superiore nel ridurre l'incidenza dei seguenti outcomes: Incidenza di nuove fratture vertebrali o peggioramento di quelle esistenti. Incidenza ni fratture cliniche Incidenza della fragilità non-vertebrale Incidenza delle maggiori fratture non vertebrali quali bacino, radio, omero, coste, pelvi e anche.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Postmenopausal women ≥ 45 years of age at the time of entry into the trial, whose last menstrual period occurred at least 2 years prior to entry into the trial, and are sufficiently mobile to complete study visits. Women < 55 years of age in whom a bilateral oophorectomy cannot clearly be documented must have their postmenopausal status confirmed by a serum FSH level > 40 IU/L and serum estradiol level < 20 pg/mL or < 73 pmol/L. XML File Identifier: QHYNa2L0rJzZ8vcCnePIs0U/HqU= Page 15/27 A minimum of 2 moderate (SQ2) or 1 severe (SQ3) vertebral fragility fractures, confirmed by the central reader. AP lumbar spine, total hip or femoral neck BMD ≥ 1.5 SD below the average BMD for young healthy, non-Hispanic, Caucasian women (Tscore ≤ –1.5 SD). Absolute BMD values will be applied to determine patient eligibility. Without language barrier, cooperative, able to come to the clinic for all follow-up visits; has given informed consent before entering the study and after being informed of the medications and procedures to be used in this study. In the opinion of the investigator, is willing to be trained and to use the pen injector daily, is able to satisfactorily use a pen-type injection delivery system, or is willing to receive daily subcutaneous injections from a caregiver who has been trained to use the pen injector.

Donne di età maggiore o uguale a 45 anni in postmenopausa al momento dell'ingresso nello studio, per le quali il ciclo mestruale si assente da almeno 2 anni, e che abbiano sufficiente motilità per completare le visite di studio. Donne di età inferiore ai 55 anni che abbiano ricevuto un'ooforectomia non chiaramente documentata dovranno confermare il loro status di postmenopausa confermato livelli di FSH sierico inferiori a 40IU/L e di estradiolo sierico inferiori a 20 pg/mL o minori di 73 pmol/L. Un minimo di due fratture vertebrali moderate (SQ2) o di 1 severa (SQ3). BMD della spina lombare AP, del bacino e del collo del femore inferiore o uguale ad 1.5 SD sotto la media per donne giovani sane, non ispaniche e caucasiche (T-score minore o uguale ad 1.5 SD).I valori assoluti di BMD verranno applicati per l'elegibilità dei pazienti. Non esistano barriere linguistiche o cooperative per la compliant alle visite; abbiano dato consenso all'arruolamento dopo essere stati informati delle procedure mediche e cliniche cui verranno sottoposti. Nell'opinione degli investigatori, abbiano la volontà di ricevere le istruzioni necessarie per l'utilizzo della penna per l'iniezione giornaliera, e siano sufficientemente in grado di utilizzare il dispositivo, o abbiano la volontà di ricevere tale procedura da parte di una terza persona opportunamente istruita.

E.4

Principal exclusion criteria

Increased baseline risk of osteosarcoma. This includes patients with Paget's disease of the bone, previous primary skeletal malignancy, or skeletal exposure to therapeutic irradiation. As elevation of serum alkaline phosphatase activity may indicate the presence of Paget's disease, an unexplained elevation of this enzyme activity will also be exclusionary. History of unresolved skeletal diseases that affect bone metabolism, other than osteoporosis, including renal osteodystrophy, osteomalacia, hyperparathyroidism (uncorrected), hypoparathyroidism, and intestinal malabsorption. Abnormally elevated values of serum albumin-corrected calcium levels at baseline, defined as ≥ 10.6 mg/dL (or ≥ 2.65 mmol/L). Abnormally low values of serum albumin- corrected calcium levels at baseline, defined as < 8.0 mg/dL (or < 2.0 mmol/L). Abnormally elevated values of serum intact PTH(1-84) at baseline defined as > 72 pg/mL (or > 7.6 pmol/L). Severe vitamin D deficiency at baseline defined as 25-hydroxy-vitamin D levels < 9.2 ng/mL (or < 23 nmol/L). Abnormal thyroid function not corrected by therapy. History of malignant neoplasms in the 5 years prior to Visit 2, with the exception of superficial basal cell or squamous cell carcinomas of the skin that have been definitively treated. Multiple myeloma or metastases to bone. Active liver disease or clinical jaundice. Significantly impaired hepatic or renal function. History of nephrolithiasis or urolithiasis within 1 year prior to the randomization. Considered imminent candidates for kyphoplasty or vertebroplasty before randomization. Patients who have been treated with kyphoplasty or vertebroplasty at 3 or more levels before randomization. Patients who have been treated with kyphoplasty or vertebroplasty within the last 6 months before randomization. Patients with history of osteonecrosis of the jaw or who are, according to the clinical judgment of the investigator, at high risk to develop osteonecrosis of the jaw, including poor oral hygiene, scheduled invasive dental procedures, high doses of bisphosphonates and/or chemotherapy to treat malignancy. Patients with history of atypical subtrochanteric or diaphyseal femoral fractures. Active or recent history of significant upper gastrointestinal disorders, such as esophageal disorders which delay esophageal transit or emptying. Unable to stand or sit in the upright position for at least 30 minutes. Prior treatment with PTH, teriparatide, or other PTH analogs; or prior participation in any other clinical trial studying PTH, teriparatide, or other PTH analogs.

Incremento basale di osteosarcoma. Con l'inclusione di pazienti affetti dalla sindrome di Paget's. Anamnesi di patologie scheletriche non completamente risolte che affliggano il metabolismo osseo, oltre all'osteoporosi, l'osteodistrofia renale, l'osteomalacia, iperparatiroidismo(non corretto), ipoparatiroidismo e malassorbimento intestinale. valori anormali di incremento di serum albumin-corrected calcium levelli al basale, definiti come ≥ 10.6 mg/dL (o ≥ 2.65 mmol/L). Decremento anormale dei valori dei livelli di serum albumin- corrected calcium al basale definiti come <8 mg7dL( o <2.0 mmol/L). Incremento anormale dei valori di PTH sierico (1-84) al basale definito come > 72 pg/mL (o > 7.6 pmol/L). Grave abbassamento dei valori di Vitamina D basale definiti come livelli di 25-idrossi-vitamina D < 9.2 ng/mL (o < 23 nmol/L). Alterata funzionalità tiroidea non corretta. Anamnesi di neoplasie maligne nei 5 anni precedenti la visita 2. Alterazioni epatiche o itterizia. Significative disfunzioni epatiche e renali.Anamnesi di nefrolitiasi o urolitiasi nell'anno precedente l'arruolamento. Candidati imminenti a kifoplastico o vertebroplastica. Pazienti trattati con kifoplastica o vertebroplastica a 3 o più livelli prima dell'arruolamento ed entro i 6 mesi dalla randomizzazione. Pazienti con una storia di osteonecrosi della mascella. Pazienti con una storia di fratture subtrocanteriche atipiche o diafisi femorale. Significativie disfunzionalità dell'apparato gastrico superiore recenti o ancora attive, che impediscano il corretto transito esofageo e lo svuotamento dello stesso. Incapacità a mantenere una posizione eretta per un tempo superiore ai 30 minuti. Precedente trattamento con PTH, teriparatide o analoghi del PTH.

E.5 End points

E.5.1

Primary end point(s)

Incidence of new vertebral fractures

Incidenza di nuove fratture vertebrali

E.5.1.1

Timepoint(s) of evaluation of this end point

During the 24-month treatment phase

Durante la fase di trattamento di 24 mesi

E.5.2

Secondary end point(s)

Key secondary fracture endpoints : Incidence of pooled new and worsening vertebral fractures. Incidence of pooled clinical fractures. Incidence of non-vertebral fragility fractures. Incidence of major non-vertebral fragility fractures: hip, radius, humerus, ribs, pelvis, and ankle.

E.5.2.1

Timepoint(s) of evaluation of this end point

During the 24-month treatment phase

Durante la fase di trattamento di 24 mesi

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

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)

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

E.8.1.3

Single blind

Yes

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

Argentina

United States

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

Ultima visita dell'ultimo soggetto arruolato nello studio

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

Number of subjects for this age range:

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)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

932

F.4.2.2

In the whole clinical trial

1340

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)

Standard for osteoporosis

Programma di trattamento standard per l'Osteoporosi

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

2012-07-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-19

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
Orphan Designation Number:
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