Clinical Trials Register

Summary
EudraCT Number:	2004-000485-13
Sponsor's Protocol Code Number:	2003100 - HMR4003I/3001
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:	2006-05-30
Trial 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

Belgium - FPS Health-DGM

A.2

EudraCT number

2004-000485-13

A.3

Full title of the trial

A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group Study of
One-year Duration Followed by 2 Years of Open-label Treatment to Determine the Safety and Efficacy of Orally Administered 2.5 mg or 5.0 mg Daily Risedronate,
in Children ≥ 4 to < 16 Years Old with Osteogenesis Imperfecta.

A.3.2

Name or abbreviated title of the trial where available

POISE

A.4.1

Sponsor's protocol code number

2003100 - HMR4003I/3001

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Procter & Gamble Ltd
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Information not present in EudraCT
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	risedronate sodium 2.5mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	risedronic acid
D.3.9.1	CAS number	115436-72-1
D.3.9.2	Current sponsor code	NE-58095
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	2.5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	Information not present in EudraCT
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	Information not present in EudraCT
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	Risedronate sodium 5mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	risedronic acid
D.3.9.1	CAS number	115436-72-1
D.3.9.2	Current sponsor code	NE-58095
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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	Information not present in EudraCT

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	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

Osteogenesis Imperfecta

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to determine the efficacy of risedronate compared to placebo in children ≥ 4 to < 16 years of age with osteogenesis imperfecta (OI) as assessed by % change from Baseline in lumbar spine BMD at Month 12.

E.2.2

Secondary objectives of the trial

a) to evaluate the efficacy of risedronate compared to placebo in children ≥ 4 to < 16 year of age with OI as assessed by:
• % change from Baseline in lumbar spine BMD at Month 6
• % change from Baseline in total body BMD
• % change from Baseline in total body and lumbar spine BMC
• change and % change from Baseline in total body and lumbar spine BMD Z score
• % change from Baseline in lumbar spine and total body bone area
• incidence and rate of new vertebral fractures
• incidence and rate of clinical vertebral and non-vertebral fractures
• percent change from Baseline in bone turnover markers
• improvement from Baseline in musculoskeletal pain relief
• improvement from Baseline in Quality of Life (QOL

b) to evaluate the safety and tolerability of risedronate treatment in children ≥ 4 to < 16 year of age with OI as assessed by:
• adverse events
• laboratory profiles including bone biopsy
• change from Baseline in bone age
• annualized growth velocity from Baseline

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

To be enrolled in this study, a child must meet the following:
a) diagnosed with OI as based on a modified classification scale7,8 (Appendix 1)
b) aged 4 through 15 years (≥ 4 to < 16), inclusive
c) have an increased risk of fractures as defined by:
• a history of at least 1 radiographically confirmed, non-traumatic or low impact
fracture, plus low BMD (Z-score ≤ -1 at either total body or lumbar spine sites);
or
• very low BMD (Z-score ≤ -2.0 at either total body or lumbar spine sites) with or
without a history of fractures
d) have at least 2 evaluable lumbar spine vertebral bodies (L1-L4), namely without fracture or degenerative disease
e) if female, post-menarche and sexually active, must be willing to agree to use a reliable contraceptive measure for the duration of the study. Acceptable forms of contraception include oral, injected or implanted contraceptives, or intrauterine devices.
f) if female and post-menarche, must have a negative serum and urine pregnancy test at Screening
g) able and willing to participate in the study as evidenced by a parent/legal guardian signing a valid written informed consent and the patient signing an assent (if appropriate).

E.4

Principal exclusion criteria

a) body weight < 10 kg
b) history of cancer within the past 5 years
c) untreated rickets within 1 year prior to enrollment
d) history of clinically significant organic or psychiatric disease or findings on physical
examination, which in the opinion of the Investigator, would prevent the patient from
completing the study
e) documented history of an abnormal or allergic reaction to bisphosphonates
f) abuse of alcohol
g) abuse of prescription or illicit drugs
h) history of using any of the following medications, regardless of dose, for at least
1 month, within 3 months of enrollment:
• anabolic agents
• estrogen (except contraceptives)
• progestogens (except contraceptives)
• calcitriol, calcidiol, or alfacalcidol
• calcitonin
• fluoride (except dental health products)
• glucocorticoids (does not include inhaled glucocorticoids)
• growth hormones
• parathyroid hormone (PTH)
• strontium
i) history of using any bisphosphonates within 1 year of enrollment, except for a single dose of oral bisphosphonate, such as risedronate or alendronate
j) osteoporosis, secondary to diseases other than OI or drug therapies
k) clinically significant abnormal laboratory finding at Screening, as follows:
• liver function test (LFT), either AST or ALT > 2 x ULN
• thyroid stimulating hormone (TSH) and PTH outside of the normal reference range
Note: An iPTH level below the lower limit of the normal range may be associated
with calcium supplementation. Therefore, the Investigator and the Medical Monitor
will review the patient's personal data and medical history to confirm or refute that
the low iPTH level is associated with high calcium supplementation
• serum 25(OH) vitamin D < 20 nmol/L (8 ng/mL)
• serum creatinine > 106 µmol/L (1.2 mg/dL)
l) current use of anticonvulsant medication
m) current use of anticoagulant medication
n) participation in another clinical trial within 3 months of enrollment.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the percent change from Baseline in lumbar spine BMD at Month 12.

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

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

Information not present in EudraCT

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Information not present in EudraCT

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

Yes

E.8.1.7.1

Other trial design description

followed by open-label period

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.8.3

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.8.5

The trial involves multiple Member States

Yes

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

Information not present in EudraCT

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

Please refe to section 5.4 in the study protocol

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

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)

Yes

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.2

Adults (18-64 years)

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

Information not present in EudraCT

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Trial subjects are under 18 years of age

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

F.4.2.2

In the whole clinical trial

124

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

2006-06-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-08-22

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

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