Back to resultsA Single and Multiple-Dose Study of MK-8521 in Healthy and Obese Males (MK-8521-002)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-8521 35μg
MK-8521 100μg
MK-8521 125μg
MK-8521 150μg
MK-8521 175μg
MK-8521 200μg
MK-8521 300μg
MK-8521 50/72μg
MK-8521 72/125μg
MK-8521 100/150μg
MK-8521 125/150μg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- Males of either 18 to 45 or 45 to 70 years of age depending on the component of the study
- Body Mass Index between either 18-25 or 30-40 kg/m^2 depending on the component of the study
- Is in good health
- Is a non-smoker and/or has not used nicotine for at least 3 months
Exclusion Criteria:
- Is mentally or legally incapacitated, has significant emotional problems or has a history of psychiatric disorders in the past 5 years
- Has a history of the following abnormalities or diseases: endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological.
- History of cancer
- History of significant multiple or severe allergies or has had an anaphylactic reaction or significant intolerability to drugs or food
- Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
- Had major surgery, donated or lost 1 unit (500 mL) of blood or participated in another study within prior 4 weeks
- Has irritable bowel disease or recurrent nausea, vomiting, diarrhea or abdominal pain
- History of acute or chronic pancreatitis
- Uses 2 weeks prior to trial, or anticipates using during trial, medications, drugs or herbal remedies such as St. John's Wort
- Consumes greater than 3 glasses of alcohol per day
- Consumes greater than 6 servings of caffeinated beverages per day
- Regularly uses illicit drugs or has a history of drug (including alcohol) abuse within prior 3 months
- Has known hypersensitivity to glucagon or any glucagon like peptide 1 (GLP-1) receptor agonist
- Is unwilling/unable to consume standardized meals and/or is on a carbohydrate restricted diet
- Has history of hypersensitivity to pharmacologic insulins
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Arm 16
Arm 17
Arm 18
Arm 19
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Part 1 - Panel A - MK-8521 100μg > PBO
Part 1 - Panel A - PBO > MK-8521 300μg
Part 1 - Panel A - MK-8521 100μg > MK-8521 300μg
Part 1 - Panel B - MK-8521 150μg > PBO > MK-8521 175μg
Part 1- Panel B- MK-8521 150μg > MK-8521 200μg > MK-8521 175μg
Part 1 - Panel B - MK-8521 150μg > MK-8521 200μg > PBO
Part 1 - Panel B - PBO > MK-8521 200μg > MK-8521 175μg
Part 2 - Panel C - MK-8521 50μg > MK-8521 72μg
Part 2 - Panel D - MK-8521 100μg > MK-8521 150μg
Part 2 - Panel E - MK-8521 125μg > MK-8521 150μg
Part 2 - Panel F - MK-8521 72μg > MK-8521 125μg
Part 2 - Panels C+D+E - Pooled Placebo
Part 2 - Panel F - Placebo
Part 3 - Panel H - MK-8521 125μg > MK-8521 35μg > PBO
Part 3 - Panel H - MK-8521 35μg > PBO > MK-8521 125μg
Part 3 - Panel H - PBO > MK- 8521 125μg > MK-8521 35μg
Part 3 - Panel H - PBO > MK- 8521 35μg > MK-8521 125μg
Part 3 - Panel H - MK-8521 125μg > PBO > MK-8521 35μg
Part 3 - Panel H - MK-8521 35μg > MK-8521 125μg > PBO
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg in the first treatment period, and matching placebo (PBO) in the second treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, and MK-8521 300μg in the second treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg in the first treatment period, and MK-8521 300μg in the second treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, PBO in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, MK-8521 200μg in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, MK-8521 200μg in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received PBO in the first treatment period, MK-8521 200μg in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 50μg Days 1 to 5 and MK-8521 72μg Days 6 to 10 in a single treatment period.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg Days 1 to 5 and MK-8521 150μg Days 6 to 10 in a single treatment period.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg Days 1 to 5 and MK-8521 150μg Days 6 to 10 in a single treatment period.
Obese male participants of 45 to 65 years of age received a single dose of MK-8521 72μg Days 1 to 7 and MK-8521 125μg Days 8 to 14 in a single treatment period.
Healthy male participants of 18 to 45 years of age received PBO once daily for 10 days.
Obese male participants of 45 to 65 years of age received a single dose of PBO Days 1 to 14.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg (high dose) in the first treatment period, MK-8521 35μg (low dose) in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 35μg (low dose) in the first treatment period, PBO MK-8521 in the second treatment period, and 125μg (high dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, MK- 8521 125μg (high dose) in the second treatment period, and MK-8521 35μg (low dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, MK- 8521 35μg (low dose) in the second treatment period, and MK-8521 125μg (high dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg (high dose) in the first treatment period, PBO in the second treatment period, and MK-8521 35μg (low dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 35μg (low dose) in the first treatment period, MK-8521 125μg (high dose) in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Outcomes
Primary Outcome Measures
Number of Participants Who Experienced at Least One Adverse Event (AE) (Part 1)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Number of Participants Who Discontinued Treatment Due to an AE (Part 1)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Area Under the Concentration Time Curve of MK-8521 From 0 to Infinity (AUC0-∞) After a Single Dose (Part 1)
AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 [100-300μg]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.
Peak Plasma Concentration (Cmax) of Participants Treated With a Single Dose of MK-8521 (Part 1)
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 [100-300μg]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.
Time Taken to Reach Cmax (Tmax) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 1)
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 [100-300μg]) is presented. No pharmacokinetic analysis was performed on participants receiving Placebo.
Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 1)
Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 [100-300μg]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.
Number of Participants With an Adverse Event (AE) (Part 2)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Number of Participants Who Discontinued Treatment Due to an AE (Part 2)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
AUC 0-24hr for Plasma Concentration of Participants Treated After Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)
AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part II, Panel C, D, and E) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.
AUC 0-24hr for Plasma Concentration of Participants Treated After Multiple Doses of MK-8521 (Part 2, Panel F)
AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.
Cmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, E and F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C-E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.
Cmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.
Trough Plasma Concentration (Ctrough) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)
Trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration]). Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.
Trough Plasma Concentration (Ctrough) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration]). Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.
Tmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.
Tmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections occurred at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.
Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part C, D, and E)
Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). Apparent terminal t1/2 was not reported for certain days since the terminal phase was not adequately captured with sampling up to 24hr post dose. No pharmacokinetic analysis was performed on participants receiving Placebo. Blood was collected for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.
Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part F)
Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). Apparent terminal t1/2 was not reported for certain days since the terminal phase was not adequately captured with sampling up to 24hr post dose. No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections occurred at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.
Number of Participants With an Adverse Event (AE) (Part 3)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Number of Participants Who Discontinued Treatment Due to an AE (Part 3)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Average Concentration (Cave) of MK-8521 Corresponding to Slope of Insulin Secretion Rate/Glucose (ISR/G) During Graded Glucose Infusion (GGI) at Tmax After a Single Dose of MK-8521 (Part 3)
Pancreatic beta cell sensitivity to ambient glucose concentration after a single dose of MK-8521 125μg/35μg or placebo at Tmax was quantified as the slope of insulin secretion rate relative to glucose concentration (ISR/G) during GGI (160 minutes duration) and assessed against MK-8521 average plasma concentration (Cave) during the GGI to preliminarily characterize the PK/ pharmacodynamic (PD) relationship. Study drug was administered on Day -1. Plasma concentrations of MK-8521 were determined at -10 min pre-GGI and 40, 80, 120 & 160 min and blood concentrations of glucose, insulin & C-peptide were determined at -10, -5 (pre-GGI), 20, 40, 60, 80, 100, 120, 140 & 160 minutes after start of GGI on Day 1 of each period. ISR calculated by deconvolution of C-peptide concentrations using a two-compartmental model was regressed on glucose concentration via simple linear regression; beta cell glucose sensitivity was defined as slope from the regression line.
Secondary Outcome Measures
Change From Baseline in Time-weighted Average From 0 to 24 Hrs (TWA0-24hr) of Heart Rate (HR) After a Single Dose of MK-8521 (Part 1)
Heart rate was assessed on Day 1 (predose & 1, 4, 8, 12, 16 & 24 hrs. postdose) & Day 2 (36 & 48 hrs. postdose). Predose and postdose HR were assessed using triplicate and duplicate measurements, respectively. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of HR on Day 1 & Day 2 of MK-8521 single dosing was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr HR was calculated for each participant where baseline was defined as predose baseline on Day 1.
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Systolic Blood Pressure (SBP) of Participants Treated With A Single Dose of MK-8521 (Part 1)
Systolic blood pressure was assessed on Day 1 (predose and 1, 4, 8, 12, 16 and 24 hrs. postdose) and Day 2 (36 and 48 hrs. postdose). Predose and postdose SBP were assessed using triplicate and duplicate measurements, respectively. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr. of SBP on Day 1 and Day 2 of MK-8521 single dosing was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr SBP was calculated for each participant where baseline was defined as predose baseline on Day 1.
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Diastolic Blood Pressure (DBP) of Participants Treated With A Single Dose of MK-8521 (Part 1)
Diastolic blood pressure was assessed on Day 1 (predose and 1, 4, 8, 12, 16 & 24 hrs postdose) and Day 2 (36 and 48 hrs postdose). Predose and postdose DBP were assessed using triplicate and duplicate measurements, respectively. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of DBP on Day 1 and Day 2 of MK-8521 single dosing was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr DBP was calculated for each participant where baseline was defined as predose baseline on Day 1.
Change From Baseline in TWA 0-24 Hrs. Heart Rate (HR) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel C, D, and E)
Heart rate was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs post admission), Day 1 and Day 6 (predose and 2, 4, 6, 8, 12, 16, 24, 36 and 48 hrs postdose) and Day 10 (predose & 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose HR on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 6, and Day 10 HR were assessed using duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of HR on Day 1, Day 6, and Day 10 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs). The change from baseline TWA0-24hr HR was calculated for each participant using TWA0-24hr on Day -1 as the baseline.
Change From Baseline in TWA 0-24 Hrs. Heart Rate (HR) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Heart rate was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs post admission), Day 1 & Day 8 (predose and 2, 4, 6, 8, 12, 16, 24, 36, and 48 hrs. post dose) & Day 14 (predose and 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose HR on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 8, and Day 14 HR were assessed as duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of HR on Day 1, Day 8, and Day 14 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr. HR was calculated for each participant using TWA0-24hr. on Day -1 as the baseline.
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Systolic Blood Pressure (SBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)
Systolic blood pressure was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs. post admission), Day 1 and Day 6 (predose & 2, 4, 6, 8, 12, 16, 24, 36, and 48 hrs. postdose) and Day 10 (predose & 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose SBP on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 6, and Day 10 SBP were assessed using duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr SBP on Day 1, Day 6 and Day 10 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs). The change from baseline TWA0-24hr SBP was calculated for each participant using TWA0-24hr on Day -1 as the baseline.
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Systolic Blood Pressure (SBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Systolic blood pressure was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs. post admission), Day 1 and Day 8 (predose and 2, 4, 6, 8, 12, 16, 24, 36, and 48 hrs. post dose) and Day 14 (predose and 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose SBP on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 8, and Day 14 SBP were assessed as duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of SBP on Day 1, Day 8, and Day 14 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr SBP was calculated for each participant using TWA0-24hr on Day -1 as the baseline.
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Diastolic Blood Pressure (DBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part C, D, and E)
Diastolic blood pressure was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs. post admission), Day 1 and Day 6 (predose and 2, 4, 6, 8, 12, 16, 24, 36 and 48 hrs. postdose) and Day 10 (predose and 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose DBP on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 6, and Day 10 DBP were assessed using duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr. DBP on Day 1, Day 6, and Day 10 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr DBP was calculated for each participant using TWA0-24hr. on Day -1 as the baseline.
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Diastolic Blood Pressure (DBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Diastolic blood pressure was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs. post admission), Day 1 and Day 8 (predose and 2, 4, 6, 8, 12, 16, 24, 36, and 48 hrs. post dose) and Day 14 (predose and 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose DBP on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 8, and Day 14 DBP were assessed as duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of DBP on Day 1, Day 8, Day 14 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs). The change from baseline TWA0-24hr. DBP was calculated for each participant using TWA0-24hr. on Day -1 as the baseline.
Slope of Insulin Secretion Rate/Glucose (ISR/G) During Graded Glucose Infusion (GGI) at Tmax After a Single Dose of MK-8521 (Part 3)
Pancreatic beta cell sensitivity to ambient glucose concentration after a single dose of MK-8521 125μg/35μg or placebo at Tmax was quantified as the slope of insulin secretion rate relative to glucose concentration (ISR/G) during GGI (160 minutes duration). Study drug was administered on Day -1 and blood concentrations of glucose, insulin & C-peptide were determined at -10, -5 (pre-GGI), 20, 40, 60, 80, 100, 120, 140, and 160 minutes after start of GGI on Day 1 of each period. ISR calculated by deconvolution of C-peptide concentrations using a two compartmental model was regressed on glucose concentration via simple linear regression; beta cell glucose sensitivity was defined as slope from the regression line.
Ratio of ISR/G at the Highest Glucose Infusion Rate During GGI Due to Treatment With A Single Dose of MK-8521 (Part 3)
Pancreatic beta cell sensitivity to ambient glucose concentration after a single dose of MK-8521 125μg/35μg or placebo at Tmax was quantified as the ratio of the insulin secretion rate to glucose (ISR/G) at the highest glucose infusion rate during GGI (i.e., time weighted average between 120 to 160 minutes [TWA120-160min] of ratio [ISR/G]). Study drug was administered on Day -1 and blood concentrations of glucose, insulin, and C-peptide were determined at -10, -5 (pre-GGI), 20, 40, 60, 80, 100, 120, 140, and 160 minutes after start of GGI on Day 1 of each period.
Glucose (TWA0-160min) During GGI at Tmax After a Single Dose of MK-8521 (Part 3)
Glycemic effect during GGI after administration of a single dose of MK 8521 125mcg/35mcg or placebo at Tmax was evaluated as the time-weighted average of glucose concentration throughout the 160 minutes (TWA0-160min) of the GGI. Study drug was administered on Day -1 and blood glucose concentrations were determined at -10, -5 (pre GGI), 20, 40, 60, 80, 100, 120, 140, 160 minutes after start of GGI on Day 1 of each period. The parameter glucose (TWA0-160min) reflects ambient glucose concentration during the GGI.
Maximum Glycemic Excursion (Gmax) During GGI and Tmax After a Single Dose of MK-8521 (Part 3)
Glycemic effect during GGI after administration of a single dose of MK-8521 125μg/35μg or placebo at Tmax was evaluated as the Gmax during the GGI. Study drug was administered on Day -1 and blood glucose concentrations were determined at -10, -5 (pre-GGI), 20, 40, 60, 80, 100, 120, 140, and 160 minutes after start of GGI on Day 1 of each period. The parameter Gmax reflects ambient glucose concentration during the GGI.
Area Under the Curve (AUC) 0-∞ for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3)
AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part III [35 and 125 μg]) is presented. Method of dispersion is actually Coefficient of Variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. No pharmacokinetic data was available for AUC0-∞ for Part 3 due to sparse issues during the treatment period.
Area Under the Curve (AUC) 0-24hr. for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3)
AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part II, Panel C, D, and E) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. No pharmacokinetic data was available for AUC0-24hr. for Part 3 due to sampling issues during the treatment period.
Peak Plasma Concentration (Cmax) of Participants Treated With a Single Dose of MK-8521 (Part 3)
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part III [35 and 125 μg]) is presented. Method of dispersion is actually Coefficient of Variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.
Time Taken to Reach Cmax (Tmax) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3)
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part III [35 and 125 μg]) is presented. No pharmacokinetic analysis was performed on participants receiving Placebo.
Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3)
Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part III [35 and 125 μg]) is presented. Method of dispersion is actually Coefficient of Variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. No pharmacokinetic data was available for t1/2 for Part 3 due to sampling issues during the treatment period.
Full Information
NCT ID
NCT02055547
First Posted
February 4, 2014
Last Updated
June 17, 2020
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02055547
Brief Title
A Single and Multiple-Dose Study of MK-8521 in Healthy and Obese Males (MK-8521-002)
Official Title
A Single and Multiple-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8521 in Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
May 10, 2013 (Actual)
Primary Completion Date
September 17, 2013 (Actual)
Study Completion Date
September 17, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MK-8521.
Part 1 primary hypothesis: Administration of single subcutaneous (SC) doses of MK-8521 is sufficiently safe and well- tolerated in healthy participants, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation.
Part 2: Administration of multiple once daily SC doses of MK-8521 is sufficiently safe and well-tolerated in healthy lean and obese participants, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation.
Detailed Description
This was a 3 part, randomized, single and multiple ascending-dose trial that evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of MK-8521 in healthy non-obese male (Part 1-Panels A and B, Panels C, D, and E of Part 2, and Part 3 Panel H) participants between the ages of 18 and 45 years and obese male participants (Part 2, Panel F) 45 to 65 years of age. An optional Panel G in Part 2 per protocol did not occur.
Part 1 was a single rising dose study to assess the safety and pharmacokinetics of single subcutaneous (SC) doses of MK-8521. Two panels of 8 healthy young non-obese male participants were dosed in up to 3 alternating dosing periods of MK-8521 or placebo (in a 6:2 ratio). Participants had a minimum 7 day washout between dosing periods.
Part 2 was a multiple-rising dose study to assess the safety and pharmacokinetics of multiple SC doses of MK-8521. Three panels (C-E) of 8 healthy young non-obese male participants received daily SC doses of MK-8521 or placebo (in a 6:2 ratio) as a titration regimen for 10 consecutive days. One panel (Panel F) of 8 older obese male participants received daily SC doses of MK-8521 or placebo (in a 6:2 ratio) as a titration regimen for 14 consecutive days.
Part 3 was a single dose, 3-period crossover study in 12 healthy lean male participants. Participants were randomized into 6 treatment groups and received a sequence of 3 treatments (MK-8521 at 35μg, 125μg and placebo). All participants in Part 3 received MK-8521 (high dose of 125μg and low dose of 35 μg) and placebo. There was a minimum 7 day washout between each dosing period for each individual participant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Parts 1 and 2 were parallel in design and Part 3 was crossover in design.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1 - Panel A - MK-8521 100μg > PBO
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg in the first treatment period, and matching placebo (PBO) in the second treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 1 - Panel A - PBO > MK-8521 300μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, and MK-8521 300μg in the second treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 1 - Panel A - MK-8521 100μg > MK-8521 300μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg in the first treatment period, and MK-8521 300μg in the second treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 1 - Panel B - MK-8521 150μg > PBO > MK-8521 175μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, PBO in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 1- Panel B- MK-8521 150μg > MK-8521 200μg > MK-8521 175μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, MK-8521 200μg in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 1 - Panel B - MK-8521 150μg > MK-8521 200μg > PBO
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, MK-8521 200μg in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 1 - Panel B - PBO > MK-8521 200μg > MK-8521 175μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received PBO in the first treatment period, MK-8521 200μg in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 2 - Panel C - MK-8521 50μg > MK-8521 72μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 50μg Days 1 to 5 and MK-8521 72μg Days 6 to 10 in a single treatment period.
Arm Title
Part 2 - Panel D - MK-8521 100μg > MK-8521 150μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg Days 1 to 5 and MK-8521 150μg Days 6 to 10 in a single treatment period.
Arm Title
Part 2 - Panel E - MK-8521 125μg > MK-8521 150μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg Days 1 to 5 and MK-8521 150μg Days 6 to 10 in a single treatment period.
Arm Title
Part 2 - Panel F - MK-8521 72μg > MK-8521 125μg
Arm Type
Experimental
Arm Description
Obese male participants of 45 to 65 years of age received a single dose of MK-8521 72μg Days 1 to 7 and MK-8521 125μg Days 8 to 14 in a single treatment period.
Arm Title
Part 2 - Panels C+D+E - Pooled Placebo
Arm Type
Placebo Comparator
Arm Description
Healthy male participants of 18 to 45 years of age received PBO once daily for 10 days.
Arm Title
Part 2 - Panel F - Placebo
Arm Type
Placebo Comparator
Arm Description
Obese male participants of 45 to 65 years of age received a single dose of PBO Days 1 to 14.
Arm Title
Part 3 - Panel H - MK-8521 125μg > MK-8521 35μg > PBO
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg (high dose) in the first treatment period, MK-8521 35μg (low dose) in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 3 - Panel H - MK-8521 35μg > PBO > MK-8521 125μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 35μg (low dose) in the first treatment period, PBO MK-8521 in the second treatment period, and 125μg (high dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 3 - Panel H - PBO > MK- 8521 125μg > MK-8521 35μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, MK- 8521 125μg (high dose) in the second treatment period, and MK-8521 35μg (low dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 3 - Panel H - PBO > MK- 8521 35μg > MK-8521 125μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, MK- 8521 35μg (low dose) in the second treatment period, and MK-8521 125μg (high dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 3 - Panel H - MK-8521 125μg > PBO > MK-8521 35μg
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg (high dose) in the first treatment period, PBO in the second treatment period, and MK-8521 35μg (low dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Arm Title
Part 3 - Panel H - MK-8521 35μg > MK-8521 125μg > PBO
Arm Type
Experimental
Arm Description
Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 35μg (low dose) in the first treatment period, MK-8521 125μg (high dose) in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.
Intervention Type
Drug
Intervention Name(s)
MK-8521 35μg
Intervention Description
Single dose 35μg subcutaneous (SC) injection in a treatment period (Part 3, Panel H)
Intervention Type
Drug
Intervention Name(s)
MK-8521 100μg
Intervention Description
Single dose 100μg SC injection in a treatment period (Part 1, Panel A) and (Part 2, Panel D)
Intervention Type
Drug
Intervention Name(s)
MK-8521 125μg
Intervention Description
Single dose 125μg SC injection in a treatment period (Part 2, Panel E) and (Part 3, Panel H)
Intervention Type
Drug
Intervention Name(s)
MK-8521 150μg
Intervention Description
Single dose 150μg SC injection in a treatment period (Part 1, Panel B)
Intervention Type
Drug
Intervention Name(s)
MK-8521 175μg
Intervention Description
Single dose 175μg SC injection in a treatment period (Part 1, Panel B)
Intervention Type
Drug
Intervention Name(s)
MK-8521 200μg
Intervention Description
Single dose MK-8521 200μg SC injection in a treatment period (Part 1, Panel B)
Intervention Type
Drug
Intervention Name(s)
MK-8521 300μg
Intervention Description
Single dose 300μg SC injection in a treatment period (Part 1, Panel A)
Intervention Type
Drug
Intervention Name(s)
MK-8521 50/72μg
Intervention Description
MK-8521 50μg SC injection Days 1-5 and 72μg Days 6-10 (Part 2, Panel C)
Intervention Type
Drug
Intervention Name(s)
MK-8521 72/125μg
Intervention Description
MK-8521 72μg SC injection Days 1-7 and 125μg Days 8-14 (Part 2, Panel F)
Intervention Type
Drug
Intervention Name(s)
MK-8521 100/150μg
Intervention Description
MK-8521 100μg SC injection Days 1-5 and 150μg Days 6-10 SC in a treatment period (Part 2, Panel D)
Intervention Type
Drug
Intervention Name(s)
MK-8521 125/150μg
Intervention Description
MK-8521 SC 125μg SC injection Days 1-5 and 150μg Days 6-10 (Part 2, Panel E)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to MK-8521 SC injection in a treatment period (Parts 1, 2, and 3)
Primary Outcome Measure Information:
Title
Number of Participants Who Experienced at Least One Adverse Event (AE) (Part 1)
Description
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame
From Day 1 through post-trial visit (Up to 8 weeks)
Title
Number of Participants Who Discontinued Treatment Due to an AE (Part 1)
Description
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame
Up to 8 weeks (Part 1)
Title
Area Under the Concentration Time Curve of MK-8521 From 0 to Infinity (AUC0-∞) After a Single Dose (Part 1)
Description
AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 [100-300μg]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.
Time Frame
Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-dose (Part 1)
Title
Peak Plasma Concentration (Cmax) of Participants Treated With a Single Dose of MK-8521 (Part 1)
Description
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 [100-300μg]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.
Time Frame
Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-dose (Part 1)
Title
Time Taken to Reach Cmax (Tmax) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 1)
Description
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 [100-300μg]) is presented. No pharmacokinetic analysis was performed on participants receiving Placebo.
Time Frame
Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-dose (Part 1)
Title
Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 1)
Description
Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 [100-300μg]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.
Time Frame
Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-dose (Part 1)
Title
Number of Participants With an Adverse Event (AE) (Part 2)
Description
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame
From Day 1 through post-trial visit (Up to 7 weeks)
Title
Number of Participants Who Discontinued Treatment Due to an AE (Part 2)
Description
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame
Up to 7 weeks (Part 2)
Title
AUC 0-24hr for Plasma Concentration of Participants Treated After Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)
Description
AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part II, Panel C, D, and E) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.
Time Frame
Days 1, 5 and 10 (Part 2) (Panels C, D, E)
Title
AUC 0-24hr for Plasma Concentration of Participants Treated After Multiple Doses of MK-8521 (Part 2, Panel F)
Description
AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.
Time Frame
Days 1, 7 and 14 (Part 2) (Panel F)
Title
Cmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)
Description
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, E and F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C-E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.
Time Frame
Days 1, 5 and 10 (Part 2) (Panels C, D, E)
Title
Cmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Description
AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.
Time Frame
Days 1, 7 and 14 (Part 2) (Panel F)
Title
Trough Plasma Concentration (Ctrough) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)
Description
Trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration]). Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.
Time Frame
Days 1, 5 and 10 (Part 2) (Panels C, D, E)
Title
Trough Plasma Concentration (Ctrough) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Description
Trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration]). Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.
Time Frame
Days 1, 7 and 14 (Part 2) (Panel F)
Title
Tmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)
Description
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.
Time Frame
Days 1, 5 and 10 (Part 2) (Panels C, D, E)
Title
Tmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Description
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections occurred at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.
Time Frame
Days 1, 7 and 14 (Part 2) (Panel F)
Title
Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part C, D, and E)
Description
Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). Apparent terminal t1/2 was not reported for certain days since the terminal phase was not adequately captured with sampling up to 24hr post dose. No pharmacokinetic analysis was performed on participants receiving Placebo. Blood was collected for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.
Time Frame
Days 1, 5 and 10 (Part 2) (Panels C, D, E)
Title
Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part F)
Description
Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). Apparent terminal t1/2 was not reported for certain days since the terminal phase was not adequately captured with sampling up to 24hr post dose. No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections occurred at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.
Time Frame
Days 1, 7 and 14 (Part 2) (Panel F)
Title
Number of Participants With an Adverse Event (AE) (Part 3)
Description
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame
Up to 6 weeks (Part 3)
Title
Number of Participants Who Discontinued Treatment Due to an AE (Part 3)
Description
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time Frame
Up to 6 weeks (Part 3)
Title
Average Concentration (Cave) of MK-8521 Corresponding to Slope of Insulin Secretion Rate/Glucose (ISR/G) During Graded Glucose Infusion (GGI) at Tmax After a Single Dose of MK-8521 (Part 3)
Description
Pancreatic beta cell sensitivity to ambient glucose concentration after a single dose of MK-8521 125μg/35μg or placebo at Tmax was quantified as the slope of insulin secretion rate relative to glucose concentration (ISR/G) during GGI (160 minutes duration) and assessed against MK-8521 average plasma concentration (Cave) during the GGI to preliminarily characterize the PK/ pharmacodynamic (PD) relationship. Study drug was administered on Day -1. Plasma concentrations of MK-8521 were determined at -10 min pre-GGI and 40, 80, 120 & 160 min and blood concentrations of glucose, insulin & C-peptide were determined at -10, -5 (pre-GGI), 20, 40, 60, 80, 100, 120, 140 & 160 minutes after start of GGI on Day 1 of each period. ISR calculated by deconvolution of C-peptide concentrations using a two-compartmental model was regressed on glucose concentration via simple linear regression; beta cell glucose sensitivity was defined as slope from the regression line.
Time Frame
From -10 to 160 minutes after GGI on Day 1 (Part 3)
Secondary Outcome Measure Information:
Title
Change From Baseline in Time-weighted Average From 0 to 24 Hrs (TWA0-24hr) of Heart Rate (HR) After a Single Dose of MK-8521 (Part 1)
Description
Heart rate was assessed on Day 1 (predose & 1, 4, 8, 12, 16 & 24 hrs. postdose) & Day 2 (36 & 48 hrs. postdose). Predose and postdose HR were assessed using triplicate and duplicate measurements, respectively. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of HR on Day 1 & Day 2 of MK-8521 single dosing was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr HR was calculated for each participant where baseline was defined as predose baseline on Day 1.
Time Frame
Baseline (predose), up to 24 hours post-dose on Day 1, up to 24 hours post-dose on Day 2 (Part 1)
Title
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Systolic Blood Pressure (SBP) of Participants Treated With A Single Dose of MK-8521 (Part 1)
Description
Systolic blood pressure was assessed on Day 1 (predose and 1, 4, 8, 12, 16 and 24 hrs. postdose) and Day 2 (36 and 48 hrs. postdose). Predose and postdose SBP were assessed using triplicate and duplicate measurements, respectively. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr. of SBP on Day 1 and Day 2 of MK-8521 single dosing was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr SBP was calculated for each participant where baseline was defined as predose baseline on Day 1.
Time Frame
Baseline (predose), up to 24 hours post-dose on Day 1, up to 24 hours post-dose on Day 2 (Part 1)
Title
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Diastolic Blood Pressure (DBP) of Participants Treated With A Single Dose of MK-8521 (Part 1)
Description
Diastolic blood pressure was assessed on Day 1 (predose and 1, 4, 8, 12, 16 & 24 hrs postdose) and Day 2 (36 and 48 hrs postdose). Predose and postdose DBP were assessed using triplicate and duplicate measurements, respectively. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of DBP on Day 1 and Day 2 of MK-8521 single dosing was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr DBP was calculated for each participant where baseline was defined as predose baseline on Day 1.
Time Frame
Baseline (predose), up to 24 hours post-dose on Day 1, up to 24 hours post-dose on Day 2 (Part 1)
Title
Change From Baseline in TWA 0-24 Hrs. Heart Rate (HR) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel C, D, and E)
Description
Heart rate was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs post admission), Day 1 and Day 6 (predose and 2, 4, 6, 8, 12, 16, 24, 36 and 48 hrs postdose) and Day 10 (predose & 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose HR on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 6, and Day 10 HR were assessed using duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of HR on Day 1, Day 6, and Day 10 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs). The change from baseline TWA0-24hr HR was calculated for each participant using TWA0-24hr on Day -1 as the baseline.
Time Frame
Baseline (predose; up to 16 hrs on Day -1), predose & up to 24 hours postdose on Days 1, 6, and 10
Title
Change From Baseline in TWA 0-24 Hrs. Heart Rate (HR) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Description
Heart rate was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs post admission), Day 1 & Day 8 (predose and 2, 4, 6, 8, 12, 16, 24, 36, and 48 hrs. post dose) & Day 14 (predose and 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose HR on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 8, and Day 14 HR were assessed as duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of HR on Day 1, Day 8, and Day 14 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr. HR was calculated for each participant using TWA0-24hr. on Day -1 as the baseline.
Time Frame
Baseline (predose; up to 16 hrs on Day -1), predose & up to 24 hours postdose on Days 1, 8, and 14
Title
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Systolic Blood Pressure (SBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)
Description
Systolic blood pressure was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs. post admission), Day 1 and Day 6 (predose & 2, 4, 6, 8, 12, 16, 24, 36, and 48 hrs. postdose) and Day 10 (predose & 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose SBP on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 6, and Day 10 SBP were assessed using duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr SBP on Day 1, Day 6 and Day 10 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs). The change from baseline TWA0-24hr SBP was calculated for each participant using TWA0-24hr on Day -1 as the baseline.
Time Frame
Baseline (predose; up to 16 hrs on Day -1), predose & up to 24 hours postdose on Days 1, 6, and 10
Title
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Systolic Blood Pressure (SBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Description
Systolic blood pressure was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs. post admission), Day 1 and Day 8 (predose and 2, 4, 6, 8, 12, 16, 24, 36, and 48 hrs. post dose) and Day 14 (predose and 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose SBP on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 8, and Day 14 SBP were assessed as duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of SBP on Day 1, Day 8, and Day 14 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr SBP was calculated for each participant using TWA0-24hr on Day -1 as the baseline.
Time Frame
Baseline (predose; up to 16 hrs on Day -1), up to 16 hrs on Day -1, predose & up to 24 hours postdose on Days 1, 8, and 14
Title
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Diastolic Blood Pressure (DBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part C, D, and E)
Description
Diastolic blood pressure was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs. post admission), Day 1 and Day 6 (predose and 2, 4, 6, 8, 12, 16, 24, 36 and 48 hrs. postdose) and Day 10 (predose and 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose DBP on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 6, and Day 10 DBP were assessed using duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr. DBP on Day 1, Day 6, and Day 10 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs.). The change from baseline TWA0-24hr DBP was calculated for each participant using TWA0-24hr. on Day -1 as the baseline.
Time Frame
Baseline (predose; up to 16 hrs on Day -1), predose & up to 24 hours postdose on Days 1, 6, and 10
Title
Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Diastolic Blood Pressure (DBP) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)
Description
Diastolic blood pressure was assessed on Day -1 (at 2, 4, 6, 8, 12, and 16 hrs. post admission), Day 1 and Day 8 (predose and 2, 4, 6, 8, 12, 16, 24, 36, and 48 hrs. post dose) and Day 14 (predose and 2, 4, 6, 8, 12, 16, and 24 hrs. postdose). Predose DBP on Day 1 was assessed using triplicate measurements while Day -1, Day 1 (postdose), Day 8, and Day 14 DBP were assessed as duplicate measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr of DBP on Day 1, Day 8, Day 14 of MK-8521 multiple dose treatment was calculated as the area under the measurement-time curve divided by the time period of over which the measurements were made (i.e., 24 hrs). The change from baseline TWA0-24hr. DBP was calculated for each participant using TWA0-24hr. on Day -1 as the baseline.
Time Frame
Baseline (predose; up to 16 hrs on Day -1), predose & up to 24 hours postdose on Days 1, 8, and 14
Title
Slope of Insulin Secretion Rate/Glucose (ISR/G) During Graded Glucose Infusion (GGI) at Tmax After a Single Dose of MK-8521 (Part 3)
Description
Pancreatic beta cell sensitivity to ambient glucose concentration after a single dose of MK-8521 125μg/35μg or placebo at Tmax was quantified as the slope of insulin secretion rate relative to glucose concentration (ISR/G) during GGI (160 minutes duration). Study drug was administered on Day -1 and blood concentrations of glucose, insulin & C-peptide were determined at -10, -5 (pre-GGI), 20, 40, 60, 80, 100, 120, 140, and 160 minutes after start of GGI on Day 1 of each period. ISR calculated by deconvolution of C-peptide concentrations using a two compartmental model was regressed on glucose concentration via simple linear regression; beta cell glucose sensitivity was defined as slope from the regression line.
Time Frame
From -10 to 160 minutes after GGI on Day 1
Title
Ratio of ISR/G at the Highest Glucose Infusion Rate During GGI Due to Treatment With A Single Dose of MK-8521 (Part 3)
Description
Pancreatic beta cell sensitivity to ambient glucose concentration after a single dose of MK-8521 125μg/35μg or placebo at Tmax was quantified as the ratio of the insulin secretion rate to glucose (ISR/G) at the highest glucose infusion rate during GGI (i.e., time weighted average between 120 to 160 minutes [TWA120-160min] of ratio [ISR/G]). Study drug was administered on Day -1 and blood concentrations of glucose, insulin, and C-peptide were determined at -10, -5 (pre-GGI), 20, 40, 60, 80, 100, 120, 140, and 160 minutes after start of GGI on Day 1 of each period.
Time Frame
From -10 to 160 minutes after GGI on Day 1
Title
Glucose (TWA0-160min) During GGI at Tmax After a Single Dose of MK-8521 (Part 3)
Description
Glycemic effect during GGI after administration of a single dose of MK 8521 125mcg/35mcg or placebo at Tmax was evaluated as the time-weighted average of glucose concentration throughout the 160 minutes (TWA0-160min) of the GGI. Study drug was administered on Day -1 and blood glucose concentrations were determined at -10, -5 (pre GGI), 20, 40, 60, 80, 100, 120, 140, 160 minutes after start of GGI on Day 1 of each period. The parameter glucose (TWA0-160min) reflects ambient glucose concentration during the GGI.
Time Frame
From -10 to 160 minutes after GGI on Day 1
Title
Maximum Glycemic Excursion (Gmax) During GGI and Tmax After a Single Dose of MK-8521 (Part 3)
Description
Glycemic effect during GGI after administration of a single dose of MK-8521 125μg/35μg or placebo at Tmax was evaluated as the Gmax during the GGI. Study drug was administered on Day -1 and blood glucose concentrations were determined at -10, -5 (pre-GGI), 20, 40, 60, 80, 100, 120, 140, and 160 minutes after start of GGI on Day 1 of each period. The parameter Gmax reflects ambient glucose concentration during the GGI.
Time Frame
From -10 to 160 minutes after GGI on Day 1
Title
Area Under the Curve (AUC) 0-∞ for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3)
Description
AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part III [35 and 125 μg]) is presented. Method of dispersion is actually Coefficient of Variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. No pharmacokinetic data was available for AUC0-∞ for Part 3 due to sparse issues during the treatment period.
Time Frame
Day 1: predose, -60, -10 min pre-GGI, 40 min, 80 min, 120 min, 160 min, 360 min, and 600 min after start of GGI (Part 3)
Title
Area Under the Curve (AUC) 0-24hr. for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3)
Description
AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part II, Panel C, D, and E) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. No pharmacokinetic data was available for AUC0-24hr. for Part 3 due to sampling issues during the treatment period.
Time Frame
Day 1: predose, -60, -10 min pre-GGI, 40 min, 80 min, 120 min, 160 min, 360 min, and 600 min after start of GGI (Part 3)
Title
Peak Plasma Concentration (Cmax) of Participants Treated With a Single Dose of MK-8521 (Part 3)
Description
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part III [35 and 125 μg]) is presented. Method of dispersion is actually Coefficient of Variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.
Time Frame
Day 1: predose, -60, -10 min pre-GGI, 40 min, 80 min, 120 min, 160 min, 360 min, and 600 min after start of GGI (Part 3)
Title
Time Taken to Reach Cmax (Tmax) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3)
Description
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part III [35 and 125 μg]) is presented. No pharmacokinetic analysis was performed on participants receiving Placebo.
Time Frame
Day 1: predose, -60, -10 min pre-GGI, 40 min, 80 min, 120 min, 160 min, 360 min, and 600 min after start of GGI (Part 3)
Title
Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 3)
Description
Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part III [35 and 125 μg]) is presented. Method of dispersion is actually Coefficient of Variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. No pharmacokinetic data was available for t1/2 for Part 3 due to sampling issues during the treatment period.
Time Frame
Day 1: predose, -60, -10 min pre-GGI, 40 min, 80 min, 120 min, 160 min, 360 min, and 600 min after start of GGI(Part 3)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Males of either 18 to 45 or 45 to 70 years of age depending on the component of the study
Body Mass Index between either 18-25 or 30-40 kg/m^2 depending on the component of the study
Is in good health
Is a non-smoker and/or has not used nicotine for at least 3 months
Exclusion Criteria:
Is mentally or legally incapacitated, has significant emotional problems or has a history of psychiatric disorders in the past 5 years
Has a history of the following abnormalities or diseases: endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological.
History of cancer
History of significant multiple or severe allergies or has had an anaphylactic reaction or significant intolerability to drugs or food
Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
Had major surgery, donated or lost 1 unit (500 mL) of blood or participated in another study within prior 4 weeks
Has irritable bowel disease or recurrent nausea, vomiting, diarrhea or abdominal pain
History of acute or chronic pancreatitis
Uses 2 weeks prior to trial, or anticipates using during trial, medications, drugs or herbal remedies such as St. John's Wort
Consumes greater than 3 glasses of alcohol per day
Consumes greater than 6 servings of caffeinated beverages per day
Regularly uses illicit drugs or has a history of drug (including alcohol) abuse within prior 3 months
Has known hypersensitivity to glucagon or any glucagon like peptide 1 (GLP-1) receptor agonist
Is unwilling/unable to consume standardized meals and/or is on a carbohydrate restricted diet
Has history of hypersensitivity to pharmacologic insulins
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study 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
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Learn more about this trial
A Single and Multiple-Dose Study of MK-8521 in Healthy and Obese Males (MK-8521-002)
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