Osteoporosis
Conditions
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.
Interventions
DRUGOdanacatib
single oral dose, tablets, 10 or 50 mg
DRUGPlacebo
single oral dose, tablets
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 25 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Terminal t1/2 of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 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 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. |
| Number of Participants Who Report an Adverse Event (AE) | Up to Day 14 | 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 | 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 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 | Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, and 168 hours post-dose | 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 | Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose | 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 | Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose | 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 | Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose | 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 | 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 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 | Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, and 168 hours post-dose | 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 | Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose | 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 | Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Urinary Aminoterminal Crosslinked Telopeptide of Type 1 Collagen (uNTx/Cr) at 168 Hours Postdose | Baseline (predose Day 1) and 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. |
Participant flow
Recruitment details
Recruitment continued until the Odanacatib Development Program was discontinued on 02-Sep-2016. No participants were actively receiving treatment at the time of study discontinuation.
Pre-assignment details
The Young Adults Odanacatib 10 mg arm represents historical data from a separate study (MK-0822-007). As such, these participants were not enrolled in any part of the current MK-0822-066 study.
Participants by arm
| Arm | Count |
|---|---|
| Adolescents Odanacatib 10 mg Study drug (single oral dose of odanacatib 10 mg) was administered following at least an 8-hour fast to adolescents. | 5 |
| Adolescents Odanacatib 50 mg Study drug (single oral dose of odanacatib 50 mg) was administered following at least an 8-hour fast to adolescents. | 3 |
| Adolescents Placebo Study drug (single oral dose of placebo) was administered following at least an 8-hour fast to adolescents. | 3 |
| Young Adults Odanacatib 10 mg Study drug (single oral dose of odanacatib 10 mg) was administered following at least an 8-hour fast to young adults (historical study MK-0822-007). | 9 |
| 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. | 6 |
| Young Adults Placebo Study drug (single oral dose of placebo) was administered following at least an 8-hour fast to young adults. | 2 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Adolescents Odanacatib 10 mg | Adolescents Odanacatib 50 mg | Adolescents Placebo | Young Adults Odanacatib 10 mg | Young Adults Odanacatib 50 mg | Young Adults Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 14.8 Years FULL_RANGE 1.6 | 15.7 Years FULL_RANGE 0.6 | 16.3 Years FULL_RANGE 0.6 | 26.6 Years FULL_RANGE 1.6 | 22.3 Years FULL_RANGE 0 | 20 Years | 20.8 Years FULL_RANGE 3.4 |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants | 8 Participants | 3 Participants | 0 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 5 | 0 / 3 | 0 / 3 | 1 / 6 | 0 / 2 | 2 / 12 |
| serious Total, serious adverse events | 0 / 5 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 2 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Population: The population analyzed included all randomized participants, treated with odanacatib 50 mg, who had available t1/2 data from at least one treatment. PK parameters were not analyzed for the Placebo arms and data are presented for the Adolescents Odanacatib 10 mg arm in other outcome measures.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Adolescents Odanacatib 50 mg | Apparent Terminal Half-life (t1/2) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg | 66.9 Hours | Geometric Coefficient of Variation 30.4 |
| Young Adults Odanacatib 50 mg | Apparent Terminal Half-life (t1/2) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg | 77.3 Hours | Geometric Coefficient of Variation 20.9 |
Primary
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.
Time frame: Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Population: The population analyzed included all randomized participants, treated with odanacatib 10 mg, who had available t1/2 data from at least one treatment including young adults from historical study MK-0822-007. PK parameters were not analyzed for the Placebo arms and data are presented for the Odanacatib 50 mg arms in other outcome measures.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Adolescents Odanacatib 10 mg | Apparent Terminal t1/2 of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 80.5 Hours | Geometric Coefficient of Variation 17.9 |
| Young Adults Odanacatib 50 mg | Apparent Terminal t1/2 of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 73.0 Hours | Geometric Coefficient of Variation 23.4 |
Primary
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.
Time frame: Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, and 168 hours post-dose
Population: The population analyzed included all randomized participants, treated with odanacatib 50 mg, who had available AUC0-168 data from at least one treatment. PK parameters were not analyzed for the Placebo arms and data are presented for the Adolescents Odanacatib 10 mg arm in other outcome measures.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Adolescents Odanacatib 50 mg | 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 | 18.7 μM·hr | Geometric Coefficient of Variation 24 |
| Young Adults Odanacatib 50 mg | 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 | 21.5 μM·hr | Geometric Coefficient of Variation 39.8 |
Primary
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.
Time frame: Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Population: The population analyzed included all randomized participants, treated with odanacatib 50 mg, who had available AUC0-inf data from at least one treatment. PK parameters were not analyzed for the Placebo arms and data are presented for the Adolescents Odanacatib 10 mg arm in other outcome measures.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Adolescents Odanacatib 50 mg | 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 | 21.6 μM·hr | Geometric Coefficient of Variation 30.7 |
| Young Adults Odanacatib 50 mg | 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 | 27.2 μM·hr | Geometric Coefficient of Variation 40.4 |
Primary
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.
Time frame: Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, and 168 hours post-dose
Population: The population analyzed included all randomized participants, treated with odanacatib 10 mg, who had available AUC0-168 data from at least one treatment including young adults from historical study MK-0822-007. PK parameters were not analyzed for the Placebo arms and data are presented for the Odanacatib 50 mg arms in other outcome measures.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Adolescents Odanacatib 10 mg | AUC0-168 for Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 8.1 μM·hr |
| Young Adults Odanacatib 50 mg | AUC0-168 for Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 9.3 μM·hr |
90% CI: [0.62, 1.23]
Primary
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.
Time frame: Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Population: The population analyzed included all randomized participants, treated with odanacatib 10 mg, who had available AUC0-inf data from at least one treatment including young adults from historical study MK-0822-007. PK parameters were not analyzed for the Placebo arms and data are presented for the Odanacatib 50 mg arms in other outcome measures.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Adolescents Odanacatib 10 mg | AUC0-inf for Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 10 μM·hr |
| Young Adults Odanacatib 50 mg | AUC0-inf for Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 11.3 μM·hr |
90% CI: [0.62, 1.26]
Primary
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.
Time frame: Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Population: The population analyzed included all randomized participants, treated with odanacatib 10 mg, who had available Cmax data from at least one treatment including young adults from historical study MK-0822-007. PK parameters were not analyzed for the Placebo arms and data are presented for the Odanacatib 50 mg arms in other outcome measures.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Adolescents Odanacatib 10 mg | Cmax of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 99.6 nM |
| Young Adults Odanacatib 50 mg | Cmax of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 122.3 nM |
90% CI: [0.57, 1.16]
Primary
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 frame: Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Population: The population analyzed included all randomized participants, treated with odanacatib 50 mg, who had available Cmax data from at least one treatment. PK parameters were not analyzed for the Placebo arms and data are presented for the Adolescents Odanacatib 10 mg arm in other outcome measures.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Adolescents Odanacatib 50 mg | Maximum Plasma Concentration (Cmax) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg | 256 nM | Geometric Coefficient of Variation 30.8 |
| Young Adults Odanacatib 50 mg | Maximum Plasma Concentration (Cmax) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg | 237 nM | Geometric Coefficient of Variation 51.1 |
Primary
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.
Time frame: Up to Day 14
Population: The population analyzed consisted of all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adolescents Odanacatib 10 mg | Number of Participants Who Report an Adverse Event (AE) | 1 Participants |
| Adolescents Odanacatib 50 mg | Number of Participants Who Report an Adverse Event (AE) | 0 Participants |
| Adolescents Placebo | Number of Participants Who Report an Adverse Event (AE) | 0 Participants |
| Young Adults Odanacatib 50 mg | Number of Participants Who Report an Adverse Event (AE) | 1 Participants |
| Young Adults Placebo | Number of Participants Who Report an Adverse Event (AE) | 0 Participants |
Primary
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.
Time frame: Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Population: The population analyzed included all randomized participants, treated with odanacatib 50 mg, who had available Tmax data from at least one treatment. PK parameters were not analyzed for the Placebo arms and data are presented for the Adolescents Odanacatib 10 mg arm in other outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Adolescents Odanacatib 50 mg | Time to Cmax (Tmax) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg | 6.0 Hours |
| Young Adults Odanacatib 50 mg | Time to Cmax (Tmax) of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 50 mg | 9.0 Hours |
Primary
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.
Time frame: Hour 0 (predose), and at 1, 2, 6, 8, 12, 24, 72, 96, 120, 168, 240, and 336 hours post-dose
Population: The population analyzed included all randomized participants, treated with odanacatib 10 mg, who had available Tmax data from at least one treatment including young adults from historical study MK-0822-007. PK parameters were not analyzed for the Placebo arms and data are presented for the Odanacatib 50 mg arms in other outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Adolescents Odanacatib 10 mg | Tmax of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 6.0 Hours |
| Young Adults Odanacatib 50 mg | Tmax of Odanacatib For Adolescents and Young Adults Following a Single Oral Dose of Odanacatib 10 mg | 6.0 Hours |
Secondary
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.
Time frame: Baseline (predose Day 1) and 168 hours postdose
Population: The population analyzed included all randomized, treated participants who had available uNTx/Cr data for Baseline and 168 hours.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Adolescents Odanacatib 10 mg | Change From Baseline in Urinary Aminoterminal Crosslinked Telopeptide of Type 1 Collagen (uNTx/Cr) at 168 Hours Postdose | 0.79 nmol[BCE]/mmol[creatinine]) | Geometric Coefficient of Variation 50.68 |
| Adolescents Odanacatib 50 mg | Change From Baseline in Urinary Aminoterminal Crosslinked Telopeptide of Type 1 Collagen (uNTx/Cr) at 168 Hours Postdose | 0.40 nmol[BCE]/mmol[creatinine]) | Geometric Coefficient of Variation 232 |
| Adolescents Placebo | Change From Baseline in Urinary Aminoterminal Crosslinked Telopeptide of Type 1 Collagen (uNTx/Cr) at 168 Hours Postdose | 1.03 nmol[BCE]/mmol[creatinine]) | Geometric Coefficient of Variation 3.39 |
| Young Adults Odanacatib 50 mg | Change From Baseline in Urinary Aminoterminal Crosslinked Telopeptide of Type 1 Collagen (uNTx/Cr) at 168 Hours Postdose | 0.36 nmol[BCE]/mmol[creatinine]) | Geometric Coefficient of Variation 53.62 |
| Young Adults Placebo | Change From Baseline in Urinary Aminoterminal Crosslinked Telopeptide of Type 1 Collagen (uNTx/Cr) at 168 Hours Postdose | 0.83 nmol[BCE]/mmol[creatinine]) | Geometric Coefficient of Variation 13.53 |