PK Study in Adolescents and Young Adults Treated with Glucocorticoids

Phase 1

• Conditions: Osteoporosis; MedDRA version: 16.1Level: PTClassification code 10031282Term: OsteoporosisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

• Registration Number: EUCTR2012-003414-14-IT
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-11-11
• Last Update Posted: 3 October 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

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 ß-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).
Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 fun

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified