Back to resultsA Study of Odanacatib When Administered to Adolescents and Young Adults Treated With Glucocorticoids (MK-0822-066)
Primary Purpose
Osteoporosis
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Odanacatib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteoporosis
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Adolescents Odanacatib 10 mg
Adolescents Odanacatib 50 mg
Adolescents Placebo
Young Adults Odanacatib 50 mg
Young Adults Placebo
Arm Description
Study drug (single oral dose of odanacatib 10 mg) was administered following at least an 8-hour fast to adolescents.
Study drug (single oral dose of odanacatib 50 mg) was administered following at least an 8-hour fast to adolescents.
Study drug (single oral dose of placebo) was administered following at least an 8-hour fast to adolescents.
Study drug (single oral dose of odanacatib 50 mg) was administered following at least an 8-hour fast to young adults.
Study drug (single oral dose of placebo) was administered following at least an 8-hour fast to young adults.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01630616
Brief Title
A Study of Odanacatib When Administered to Adolescents and Young Adults Treated With Glucocorticoids (MK-0822-066)
Official Title
A Single-Dose Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Odanacatib in Adolescents and Young Adults Treated With Glucocorticoids
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Terminated
Study Start Date
March 12, 2013 (Actual)
Primary Completion Date
July 14, 2016 (Actual)
Study Completion Date
July 14, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Adolescents Odanacatib 10 mg
Arm Type
Experimental
Arm Description
Study drug (single oral dose of odanacatib 10 mg) was administered following at least an 8-hour fast to adolescents.
Arm Title
Adolescents Odanacatib 50 mg
Arm Type
Experimental
Arm Description
Study drug (single oral dose of odanacatib 50 mg) was administered following at least an 8-hour fast to adolescents.
Arm Title
Adolescents Placebo
Arm Type
Placebo Comparator
Arm Description
Study drug (single oral dose of placebo) was administered following at least an 8-hour fast to adolescents.
Arm Title
Young Adults Odanacatib 50 mg
Arm Type
Experimental
Arm Description
Study drug (single oral dose of odanacatib 50 mg) was administered following at least an 8-hour fast to young adults.
Arm Title
Young Adults Placebo
Arm Type
Placebo Comparator
Arm Description
Study drug (single oral dose of placebo) was administered following at least an 8-hour fast to young adults.
Intervention Type
Drug
Intervention Name(s)
Odanacatib
Other Intervention Name(s)
MK-0822
Intervention Description
single oral dose, tablets, 10 or 50 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
single oral dose, tablets
Primary Outcome Measure Information:
Title
Number of Participants Who Report an Adverse Event (AE)
Description
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.
Time Frame
Up to Day 14
Title
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
Description
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.
Time Frame
Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Title
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
Description
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.
Time Frame
Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, and 168 hours post-dose
Title
Maximum Plasma Concentration (Cmax) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg
Description
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.
Time Frame
Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Title
Time to Cmax (Tmax) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg
Description
Tmax is the time required to reach Cmax. PK analysis was not performed on participants receiving placebo.
Time Frame
Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Title
Apparent Terminal Half-life (t1/2) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg
Description
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.
Time Frame
Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Title
AUC0-inf for Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg
Description
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.
Time Frame
Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Title
AUC0-168 for Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg
Description
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.
Time Frame
Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, and 168 hours post-dose
Title
Cmax of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg
Description
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.
Time Frame
Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Title
Tmax of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg
Description
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.
Time Frame
Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Title
Apparent Terminal t1/2 of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg
Description
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.
Time Frame
Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Secondary Outcome Measure Information:
Title
Change From Baseline in Urinary Aminoterminal Crosslinked Telopeptide of Type 1 Collagen (uNTx/Cr) at 168 Hours Postdose
Description
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.
Time Frame
Baseline (predose Day 1) and 168 hours postdose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Learn more about this trial
A Study of Odanacatib When Administered to Adolescents and Young Adults Treated With Glucocorticoids (MK-0822-066)
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