Clinical Trials Register

Summary
EudraCT Number:	2012-003414-14
Sponsor's Protocol Code Number:	0822-066
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2012-07-31
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2012-003414-14

A.3

Full title of the trial

A Single-Dose Study to Assess the Pharmacokinetics, Pharmacodynamics,
Safety, and Tolerability of Odanacatib in Adolescents
Treated with Glucocorticoids

A.3.1

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

PK Study in Adolescents with Glucocorticoid-Induced Osteoporosis

A.4.1

Sponsor's protocol code number

0822-066

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/127/2012

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (hereafter referred to as
B.1.3.4	Country	United States
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	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (hereafter referred to as
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (hereafter referred to as
B.5.2	Functional name of contact point	Aubrey Stoch
B.5.3	Address:
B.5.3.1	Street Address	One Merck Drive
B.5.3.2	Town/ city	Whitehouse Station, NJ
B.5.3.3	Post code	0889-0100
B.5.3.4	Country	United States
B.5.4	Telephone number	732594-4405
B.5.5	Fax number	732594-3590
B.5.6	E-mail	aubrey.stoch@merck.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	Odanacatib
D.3.2	Product code	MK-0822
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	Odanacatib
D.3.9.1	CAS number	603139-19-1
D.3.9.2	Current sponsor code	MK-0822
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	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	Odanacatib
D.3.2	Product code	MK-0822
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	Odanacatib
D.3.9.1	CAS number	603139-19-1
D.3.9.2	Current sponsor code	MK-0822
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	50
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	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

osteoporosis

E.1.1.1

Medical condition in easily understood language

adolescents treated with glucocorticoids

E.1.1.2

Therapeutic area

Body processes [G] - Bones and nerves physological processes [G11]

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	10031282
E.1.2	Term	Osteoporosis
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

To assess safety and tolerability of single doses of odanacatib in mature adolescents. Compare plasma pharmacokinetic parameters[AUC0-∞, AUC0-168hr, Cmax, C168hr, Tmax, apparent terminal t1/2] following single oral doses of odanactib 10mg and 50mg between mature adolescents and healthy adult historical controls.

E.2.2

Secondary objectives of the trial

To assess effects of single oral doses of odanacatib 10 and 50 mg on urinary amnioterminal crosslinked telpeptide of Type I collagen, in mature adolescents treated with glucocorticoids. The PK/PD relationship between concentration and inhibition of uNTx/Cr levels for odanacatib in adolescents treated with glucocorticoids will be evaluated and the relationship to that seen in adults will be examined.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) The parent or guardian and subject agrees to the subject’s participation in the study as indicated by parental/guardian signature on the consent form and subject assent. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
. a Written assent will be sought from subjects of appropriate intellectual maturity. The subject is willing to comply with procedures, and is able to keep scheduled clinic visits.
2)The subject is a male or female between the ages of 12 and 18 years of age (inclusive) on the day of screening.
3) Female subjects of reproductive potential (or other female subjects at the discretion of the investigator) must demonstrate a serum β-hCG level consistent with the nongravid state at the prestudy (screening) visit and agree to use (and/or have their partner use) two (2) acceptable methods of birth control beginning at the prestudy visit throughout the study and until 2 weeks after the dose of study. Acceptable methods of birth control are two (2) of the following: intrauterine device (IUD without local hormone release), diaphragm, spermicides, cervical cap, contraceptive sponge, and /or condoms. Abstinence is an alternative life style and subjects practicing abstinence may be included in the study.
4) Subject is currently receiving glucocorticoid therapy at a dose anticipated to be stable over the course of the study period when pharmacokinetic and pharmacodynamic determinations are being made. Subject must have started glucocorticoid therapy at least approximately 3 month prior to study drug administration. The dose of glucocorticoids should be equivalent ≥5 mg/day of prednisone, other glucocorticoids may be allowable at the discretion of the investigator after consultation with the SPONSOR medical monitor.
5) Subject has radiographic evidence of closed epiphyses at the hand
6) Subject has no clinically significant abnormality on electrocardiogram (ECG) performed at the prestudy (screening).
7) Subject is a nonsmoker.
8) Subject is willing to comply with the study restrictions (see Section 3.2 for a complete summary of study restrictions).

E.4

Principal exclusion criteria

a. Subject or parent/legal guardian, is, in the opinion of the investigator, mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of a
clinically significant psychiatric disorder over the last 5 years. Subjects who have
had situational depression may be enrolled in the study at the discretion of the
investigator.
b. Female subject has a positive pregnancy test within 24 hours of study initiation or an
unwillingness to undergo pregnancy testing.
c. Subject has a history of any illness that, in the opinion of the study investigator, might
confound the results of the study or poses an additional risk to the subject by their
participation in the study.
d. Subject has an estimated creatinine clearance of ≤ 80 mL/min based on the Schwartz
equation; the Schwartz equation is:
CrCl (mL/min) = [length (cm) × k]/SCr (mg/dL),
where k = 0.55 for females age 12 to 18 years, and k = 0.7 for males age 12 to 18
years.
An actual creatinine clearance, as determined by a 24-hour urine collection, may be
used in place of, or in conjunction with, the Schwartz equation.
e. Subject’s blood pressure is >95th percentile for age and gender (see Attachment 3:
Pediatrics, Vol. 98, No. 4; 1996). Subjects with transient/intermittent blood pressure
readings >95th percentile for age and gender may be enrolled at the discretion of the
investigator.
f. Subject has a history of stroke, chronic seizures, or major neurological disorder.
g. Subjects with a history of uncomplicated kidney stones or childhood asthma may be
enrolled in the study at the discretion of the investigator.
h. Subject has a history of malignant neoplastic disease.
i. Subject is a nursing mother.
j. Subject has a serum calcium level obtained at screening that is below the lower limit
of normal.
k. The subject has any clinically significant primary growth disorder (e.g.,
achondroplasiaor growth hormone deficiency).
l. The subject has any disease affecting the stomach or proximal small intestine
resulting in malabsorption.
m. Prior to screening the subject received treatment which might have influenced bone
turnover, including:
1) Within 6 months: anabolic steroids (including DHEA and other weaker analogs),
testosterone, calcitonin, calcitriol, alfacalcidol, excess vitamin A (>10,000
units/day) or excess vitamin D (>3000 units/day), or cyclosporine.
2) Within 6 months: initiation of use of birth control pills (estrogen-progestin
combinations or progestin only, or depo provera) or other estrogen containing
products.
3) Thyroid hormone (levothyroxine, L-T4), unless on a stable dose for at least 3
months before screening, and has a normally functioning thyroid gland (is
euthyroid) as documented by an ultrasensitive thyroid stimulating hormone (TSH)
serum assay conducted at screening that is within the normal range.
4) Previous treatment with any marketed or experimental bisphosphonate within the
12 months preceding screening visit.
n. The subject has, within 3 years prior to screening, a history of, or evidence for, any
clinically relevant metabolic bone disease (other than glucocorticoid-induced bone
loss) including but not limited to primary hyperparathyroidism, hypoparathyroidism,
hyperthyroidism, osteomalacia, and osteogenesis imperfecta.
o. The subject has a history of, or evidence for, hypothyroidism, unless the subject has
been treated with a stable dose of thyroid hormone for at least 3 months immediately
prior to screening, and is euthyroid (serum TSH at screening is within the normal
range). Subjects at screening discovered to have mild hypothyroidism (slightly
elevated serum TSH) are eligible to enter the study provided they receive careful
thyroid replacement therapy, if needed, and TSH levels are monitored as appropriate
during the study.
Diet/Activity/Other
see protocol for remainder of exclusions.

E.5 End points

E.5.1

Primary end point(s)

Number of Participants who Report an Adverse Event, Area under the concentration time curve from 0 hour to infinity(
AUC0-∞) , Area under the concentration time curve from 0 hour to 168hr of Odanacatib (AUC0-168hr, ) Maximum Plasma Concentration of odanacatib (Cmax, ) Plasma Concentration at 168hours (C168hr, ) Time to Cmax of odanacatib (Tmax, ) apparent terminal t1/2 of odanacatib

E.5.1.1

Timepoint(s) of evaluation of this end point

up to day 14(AEs) Hour 0 (predose) and at 1, 2, 6, 12, 24, 72, 120, 168, 240 and 336 hours post dose

E.5.2

Secondary end point(s)

Change from baseline in inhibition of urinary aminoterminal crosslinked telopeptide of Type 1 collagen (uNTx/Cr)

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline (predose Day 1) and 168 hours post dose

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

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

for administration in pediatrics

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Canada

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

E.8.9 Initial estimate of the duration of the trial

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

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children under the age of 18

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

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 of Care per regular physicians

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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