A Study of Odanacatib When Administered to Adolescents and Young Adults Treated With Glucocorticoids (MK-0822-066)

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

This study will assess the safety, tolerability, pharmacodynamics, and pharmacokinetics of single doses of odanacatib in mature adolescents and young adults who are currently receiving glucocorticoid therapy. The primary hypotheses for the study are that a single dose of odanacatib is well tolerated in mature adolescents and following single dose administration of odanacatib 50 mg, there is no clinically important difference in AUC0-inf between mature adolescents and young adults.

Study Overview

• Status: Terminated
• Conditions: Osteoporosis
• Intervention / Treatment: Drug: Odanacatib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female participants of reproductive potential (or other female subjects at the discretion of the investigator) must have negative serum pregnancy test 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
• Receiving glucocorticoid therapy at a dose anticipated to be stable over the course of the study period
• X-ray evidence of closed epiphyses (growth plate) at the hand
• Nonsmoker

Exclusion Criteria:

• Pregnant or unwilling to undergo pregnancy test
• History of stroke, chronic seizures, or major neurological disorder
• History of malignant neoplastic disease (cancer)
• Breastfeeding
• Primary growth disorder
• Any disease affecting the stomach or proximal small intestine resulting in malabsorption
• Received treatment which might have influenced bone turnover, including anabolic steroids, testosterone, calcitonin, calcitriol, alfacalcidol, excess vitamin A or excess vitamin D, or cyclosporine or initiation of use of birth control pills (estrogen-progestin combinations or progestin only, or depo provera) or other estrogen containing medications, or thyroid hormone unless on a stable dose for at least 1 month and has a normally functioning thyroid gland
• Previous treatment with any marketed or experimental bisphosphonate within 12 months
• 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 within previous 3 years
• History of hypothyroidism
• Consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
• Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
• Has had major surgery, donated or lost 1 unit of blood (approximately 500 mL), or participated in another investigational study within 4 weeks
• History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Regular user (including "recreational use") of any illicit drugs, or has a history of drug or alcohol abuse
• Unable to swallow tablets

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adolescents Odanacatib 10 mg; Study drug (single oral dose of odanacatib 10 mg) was administered following at least an 8-hour fast to adolescents.	Drug: Odanacatib; single oral dose, tablets, 10 or 50 mg; Other Names: MK-0822
Experimental: Adolescents Odanacatib 50 mg; Study drug (single oral dose of odanacatib 50 mg) was administered following at least an 8-hour fast to adolescents.	Drug: Odanacatib; single oral dose, tablets, 10 or 50 mg; Other Names: MK-0822
Placebo Comparator: Adolescents Placebo; Study drug (single oral dose of placebo) was administered following at least an 8-hour fast to adolescents.	Drug: Placebo; single oral dose, tablets
Experimental: Young Adults Odanacatib 50 mg; Study drug (single oral dose of odanacatib 50 mg) was administered following at least an 8-hour fast to young adults.	Drug: Odanacatib; single oral dose, tablets, 10 or 50 mg; Other Names: MK-0822
Placebo Comparator: Young Adults Placebo; Study drug (single oral dose of placebo) was administered following at least an 8-hour fast to young adults.	Drug: Placebo; single oral dose, tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Report an Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to Day 14
Area Under the Plasma-Drug Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg	Area Under the Plasma-Drug Concentration/Time Curve from Time 0 to infinity (AUC0-inf) is a measure of the total amount of drug in the plasma from the dose administration to the last measurable sample. The Method of Dispersion is more accurately described as "Percent Geometric Coefficient of Variation". Pharmacokinetic (PK) analysis was not performed on participants receiving placebo.	Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Area Under the Plasma-Drug Concentration Time Curve From Hour 0 to 168 Hours (AUC0-168) For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg	Area Under the Plasma-Drug Concentration/Time Curve from Time 0 to Hour 168 (AUC0-168) is a measure of the total amount of drug in the plasma from the dose administration to the Hour 168 sample. The Method of Dispersion is more accurately described as "Percent Geometric Coefficient of Variation". PK analysis was not performed on participants receiving placebo.	Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, and 168 hours post-dose
Maximum Plasma Concentration (Cmax) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg	Cmax is a measure of the maximum amount of drug in the plasma after the drug dose is given. The Method of Dispersion is more accurately described as "Percent Geometric Coefficient of Variation". PK analysis was not performed on participants receiving placebo.	Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Time to Cmax (Tmax) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg	Tmax is the time required to reach Cmax. PK analysis was not performed on participants receiving placebo.	Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Apparent Terminal Half-life (t1/2) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg	T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. PK analysis was not performed on participants receiving placebo.	Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
AUC0-inf for Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg	Area Under the Plasma Concentration/Time Curve from Time 0 to infinity (AUC0-inf) is a measure of the total amount of drug in the plasma from the dose administration to the last measurable sample. The AUC0-inf data for 10 mg odanacatib in adolescents were compared with the historical young adult odanacatib 10 mg AUC0-inf data from study MK-0822-007. PK analysis was not performed on participants receiving placebo.	Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
AUC0-168 for Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg	Area Under the Plasma Concentration/Time Curve from Time 0 to Hour 168 (AUC0-168) is a measure of the total amount of drug in the plasma from the dose administration to the Hour 168 sample. The AUC0-168 data for 10 mg odanacatib in adolescents were compared with the historical young adult odanacatib 10 mg AUC0-168 data from study MK-0822-007. PK analysis was not performed on participants receiving placebo.	Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, and 168 hours post-dose
Cmax of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg	Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. The Cmax data for 10 mg odanacatib in adolescents were compared with the historical young adult odanacatib 10 mg Cmax data from study MK-0822-007. PK analysis was not performed on participants receiving placebo.	Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Tmax of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg	Tmax is the time required to reach Cmax. The Tmax data for 10 mg odanacatib in adolescents were compared with the historical young adult odanacatib 10 mg Tmax data from study MK-0822-007. PK analysis was not performed on participants receiving placebo.	Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Apparent Terminal t1/2 of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg	Apparent terminal t1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. The apparent terminal t1/2 data for 10 mg odanacatib in adolescents were compared with the historical young adult odanacatib 10 mg apparent terminal t1/2 data from study MK-0822-007. PK analysis was not performed on participants receiving placebo.	Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Urinary Aminoterminal Crosslinked Telopeptide of Type 1 Collagen (uNTx/Cr) at 168 Hours Postdose	Urinary aminoterminal crosslinked telopeptide of Type I collagen (uNTx/Cr) is a biochemical marker of bone resorption. Odanacatib selectively and potently inhibits cathepsin K (CatK), the primary catalyst of bone resorption. Since CatK is the enzyme responsible for bone matrix degradation it is possible to use bone resorption biomarkers to quantify pharmacodynamic effects in short term clinical studies. CatK cleaves the N-telopeptide of collagen type I to form NTx and also cleaves the serum C-terminal telopeptide of collagen type I (1-CTP - itself generated by the action of matrix metalloproteases) to generate CTx. Urine NTx measurements (in bone collagen equivalents [BCE]) have been normalized to creatinine clearance.	Baseline (predose Day 1) and 168 hours postdose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2013
• Primary Completion (Actual): July 14, 2016
• Study Completion (Actual): July 14, 2016

Study Registration Dates

• First Submitted: June 26, 2012
• First Submitted That Met QC Criteria: June 26, 2012
• First Posted (Estimate): June 28, 2012

Study Record Updates

• Last Update Posted (Actual): August 28, 2018
• Last Update Submitted That Met QC Criteria: July 30, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis
• Other Study ID Numbers: 0822-066; MK-0822-066 (Other Identifier: Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No