| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| 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 | 16.1 |
| 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 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
-To assess the safety and tolerability of single doses of odanacatib in mature adolescents.
-To compare plasma pharmacokinetic parameters [AUC0-∞, AUC0-168hr, Cmax, C168hr, Tmax, apparent terminal t½] following a single oral dose of odanacatib 10 mg (Panel A) between mature adolescents and adult historical controls and 50 mg (Panel B) between mature adolescents and young adults (Panel C). |
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| E.2.2 | Secondary objectives of the trial |
-To assess the effects of single oral dose administration of odanacatib 10 and 50 mg on urinary aminoterminal crosslinked telopeptide of Type I collagen (uNTx/Cr), a biochemical marker of bone resorption, in mature adolescents receiving glucocorticoids.
-The PK/PD relationship between concentration and inhibition of uNTx/Cr levels for odanacatib in mature adolescents treated with glucocorticoids will be evaluated and the relationship to that seen in young adults will be examined.
-To use PK, or PK/PD modeling to predict an appropriate dose in mature adolescents if neither 10 mg nor 50 mg demonstrates similarity of AUC to adult controls. |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Future Biomedical Research on DNA (blood) specimens when consent is given. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. For instance, exploratory pharmacogenetics (PGt) studies may be performed if significant Pharmacokinetic/Pharmacodynamic (PK/PD) relationships are observed or adverse events are identified. Genomic markers of disease may also be investigated. |
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| E.3 | Principal inclusion criteria |
Consent/Assent for Panels A and B only
a. The parent or guardian and subject agree 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.
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.
Or
Consent for Panel C only
a. The subject is willing to give written informed consent to participate in the trial.
b. The subject is a male or female between the ages of 12 and 17 years of age (inclusive) on the day of screening for Panels A and B only. The subject is a male or female between the ages of 18-25 years of age (inclusive) on the day of screening for Panel C only.
c. Female subjects of reproductive potential (or other female subjects at the discretion of the investigator) must demonstrate a serum or urine 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.
d. 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 1 month prior to study drug administration. The dose of glucocorticoids should be approximately 5 mg/day of prednisone or equivalent, other glucocorticoids may be allowable at the discretion of the investigator
after consultation with the SPONSOR medical monitor.
e. Subject (Panels A and B; Panel C at the discretion of the investigator and Sponsor) has radiographic evidence of closed epiphyses at the hand.
f. Subject has no clinically significant abnormality on electrocardiogram (ECG) performed at the prestudy (screening).
h. Subject is a nonsmoker.
i. Subject is willing to comply with the study restrictions (see Section 3.2 for a complete summary of study restrictions). |
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| 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. For Panels A and B only, 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 17 years, and k = 0.7 for males age 12 to 17 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.
For Panel C only, subject has an estimated creatinine clearance of ≤80 mL/min based on the Cockcroft-Gault equation; the Cockcroft-Gault equation is:
ClCr = (140-age[yr])(body wt [kg])
(72)(serum creat [mg/dL])
When creatinine is measured in micromole/litre, use the following formula:
ClCr = (140-age[yr])(body wt[kg])
(72)(serum creatinine [micromol/L] x 0.0113)
An actual creatinine clearance, as determined by a 24-hour urine collection, may be used in place of, or in conjunction with, the Cockcroft-Gault equation; subjects who have an actual or estimated creatinine clearance up to 10% below 80 mL/min may be enrolled in the study at the discretion of the investigator.
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.
Please refer to protocol for the complete list of exclusions. |
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| 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 |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| out to 14 days post dose(AEs); Hour 0 (predose) and at 1, 2, 6, 12, 24, 72, 120, 168, 240 and 336 hours post dose |
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| E.5.2 | Secondary end point(s) |
| Change from baseline in inhibition of urinary aminoterminal crosslinked telopeptide of Type 1 collagen (uNTx/Cr) |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Baseline (predose Day 1) and 168 hours post dose |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| First administration to pediatrics and PK/PD Study |
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| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 3 |
| 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 | No |
| 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 |
| Italy |
| Korea, Republic of |
| Moldova, Republic of |
| United Kingdom |
| United States |
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| E.8.7 | Trial has a data monitoring committee | No |
| 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
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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